Methods and uses of biological tissues for various stent and other medical applications

Description

BACKGROUND

To date, the small intestinal submucosa (SIS) is the major biological tissue scaffold that has garnered some biological applications to replace or augment injured or damaged biological tissues. Once the smooth muscles are stripped away, the SIS consists of largely collagen and some elastin fibers. The fixation of the tissue, however, renders the scaffold stiff and can result in losses of some of its biological advantages.

In view of the same, it would be advantageous to identify and process an effective alternative tissue that would maintain its elasticity, keep its biological advantages, and be useful for various bodily purposes, including as part of various medical devices.

BRIEF SUMMARY

In an exemplary embodiment of a method of processing pulmonary ligament tissue of the present disclosure, the method comprises the steps of acquiring a mammalian tissue comprising at least a portion of a pulmonary ligament, selecting a sample of pulmonary ligament tissue from the at least a portion of pulmonary ligament, and fixing the sample of pulmonary ligament tissue using a fixative, resulting in a fixed sample.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the method comprises the steps of acquiring a mammalian tissue comprising at least a portion of a pulmonary region tissue, selecting a sample of pulmonary region tissue from the at least a portion of a pulmonary region tissue, and fixing the sample of pulmonary region tissue using a fixative, resulting in a fixed sample. In another embodiment, the step of acquiring comprises acquiring the at least a portion of a pulmonary region tissue by way of dissecting or resecting tissue from a deceased mammal. In yet another embodiment, the step of acquiring comprises acquiring the at least a portion of a pulmonary region tissue from a mammal selected from the group consisting of a pig, a horse, a cow, a goat, a sheep, and a human. In an additional embodiment, the step of acquiring comprises acquiring the at least a portion of a pulmonary region tissue from a larger quantity of mammalian tissue comprising at least a portion of a lung, at least a portion of an aorta, and at least a portion of a pulmonary ligament.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the step of acquiring comprises acquiring the at least a portion of a pulmonary region tissue from a larger quantity of mammalian tissue comprising at least a portion of a lung, at least a portion of an esophagus, and at least a portion of a pulmonary ligament. In an additional embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting a sample of pulmonary ligament tissue from the mammalian tissue. In yet an additional embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting a sample of visceral pleura tissue from the mammalian tissue. In another embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting the sample of pulmonary region tissue from the at least a portion of a pulmonary region tissue by cleaning the at least a portion of a pulmonary region tissue to remove blood from the at least a portion of a pulmonary region tissue. In yet another embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting a sample of pulmonary ligament tissue from the at least a portion of a pulmonary region tissue by cleaning the at least a portion of a pulmonary region tissue to remove blood from the at least a portion of a pulmonary region tissue.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the step of selecting a sample of pulmonary region tissue comprises selecting a sample of visceral pleura tissue from the at least a portion of a pulmonary region tissue by cleaning the at least a portion of a pulmonary region tissue to remove blood from the at least a portion of a pulmonary region tissue. In another embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting the sample of pulmonary region tissue from the at least a portion of a pulmonary region tissue by removing fatty material from the at least a portion of a pulmonary region tissue. In yet another embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting a sample of pulmonary ligament tissue from the at least a portion of a pulmonary region tissue by removing fatty material from the at least a portion of a pulmonary region tissue. In an additional embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting a sample of visceral pleura tissue from the at least a portion of a pulmonary region tissue by removing fatty material from the at least a portion of a pulmonary region tissue.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the step of selecting a sample of pulmonary region tissue comprises selecting the sample of pulmonary region tissue from the at least a portion of a pulmonary region tissue that is free or substantially free of perforations. In an additional embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting a sample of pulmonary ligament tissue from the at least a portion of a pulmonary region tissue that is free or substantially free of perforations. In yet an additional embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting a sample of visceral pleura tissue that is free or substantially free of perforations. In another embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting the sample of pulmonary region tissue from the at least a portion of a pulmonary region tissue that is free or substantially free of blood or blood vessels.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the step of selecting a sample of pulmonary region tissue comprises selecting a sample of pulmonary ligament tissue from the at least a portion of a pulmonary region tissue that is free or substantially free of blood or blood vessels. In another embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting a sample of visceral pleura tissue that is free or substantially free of blood or blood vessels. In yet another embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting the sample of pulmonary region tissue from the at least a portion of a pulmonary region tissue that is free or substantially free of irregularities. In an additional embodiment, the step of selecting a sample of pulmonary region tissue further comprises placing the sample of pulmonary region tissue in a saline solution.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the step of selecting a sample of pulmonary region tissue further comprises placing the sample of pulmonary region tissue in a solution at least 20° F. below ambient temperature. In an additional embodiment, the method further comprises the step of placing the sample of pulmonary region tissue within or upon a mount having known dimensions, wherein the placing step is performed prior to the fixing step. In yet an additional embodiment, the step of placing the sample of pulmonary region tissue within or upon a mount is performed by placing the sample of pulmonary region tissue within or upon a circular or relatively circular mount and securing the sample of pulmonary region tissue to the mount. In another embodiment, the step of placing the sample of pulmonary region tissue within or upon a mount is performed by placing the sample of pulmonary region tissue within or upon a square or rectangular mount and securing the sample of pulmonary region tissue to the mount. In yet another embodiment, the step of placing the sample of pulmonary region tissue within or upon a mount is performed by placing the sample of pulmonary region tissue within or upon a multidimensional mount and securing the sample of pulmonary region tissue to the mount. In an additional embodiment, the fixed sample maintains or closely resembles the known dimensions of the mount.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the method further comprises the step of securing the sample of pulmonary region tissue within or upon the mount, wherein the securing step is performed prior to the fixing step. In another embodiment, the securing step performed using a securing member selected from the group consisting of one or more sutures, one or more clamps, and one or more forceps. In yet another embodiment, the step of fixing the sample of pulmonary region tissue using a fixative is performed by fixing the sample of pulmonary region tissue using the fixative selected from the group consisting of glutaraldehyde, formaldehyde, and glycerol. In an additional embodiment, the step of fixing the sample of pulmonary region tissue using a fixative is performed by fixing the sample of pulmonary region tissue using the fixative within a HEPES or phosphate buffer. In yet an additional embodiment, the step of fixing the sample of pulmonary region tissue using a fixative is performed by fixing the sample of pulmonary region tissue using a fixation procedure selected from the group consisting of aqueous fixation, cryo-preservation, and dry tissue fixation.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the method further comprises the step of placing at least two dots on the sample of pulmonary region tissue prior to performing the fixing step, wherein distance(s) between the at least two dots are known prior to performing the fixing step. In an additional embodiment, the method further comprises the step of measuring the distance(s) between the at least two dots after performing the fixing step, and comparing the distance(s) between the at least two dots after performing the fixing step to the distances between the at least two dots prior to performing the fixing step. In yet an additional embodiment, the method further comprises the step of determining an amount of shrinkage based upon data collected from the comparing step. In another embodiment, the acquiring step comprises separating the at least a portion of pulmonary region tissue.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the method further comprises the step of forming the fixed sample into a valve. In another embodiment, method further comprises the step of shaping the fixed sample so that the fixed sample will fit around portions of a frame. In yet another embodiment, the shaping step is performed by stretching the fixed tissue and cutting the fixed tissue to form a desired shape. In an additional embodiment, method further comprises the step of positioning the fixed sample upon portions of the frame, wherein the fixed sample and the frame collectively form a tissue product.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the method further comprises the step of positioning the fixed sample upon portions of a frame, wherein the fixed sample and the frame collectively form a tissue product. In an additional embodiment, method further comprises the step of securing a portion of the fixed sample to the frame using one or more sutures. In yet an additional embodiment, method further comprises the step of weaving a portion of the fixed sample around at least a portion of the frame to secure the portion of the fixed sample to the frame. In another embodiment, the weaving step is performed to secure the portion of the fixed sample to the frame without requiring sutures.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the method further comprises the step of weaving a portion of the fixed sample around at least a portion of the frame to secure the portion of the fixed sample to the frame, wherein when the tissue product is positioned within a mammalian luminal organ, the one or more sutures are not in contact with fluid flowing through the mammalian luminal organ. In another embodiment, the method further comprises the step of positioning the tissue product within a mammalian luminal organ so that fluid native to the mammalian luminal organ may pass through a lumen defined within the tissue product. In yet another embodiment, the frame comprises at least one superior arm and at least one inferior arm positioned at or near an inlet portion of the tissue product, the at least one superior arm and the at least one inferior arm configured to receive a first portion of the fixed sample thereon.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the at least one superior arm and the at least one inferior arm are configured to receive the first portion of the fixed sample thereon, and wherein the method further comprises the step of securing the first portion of the fixed sample to the frame using one or more sutures. In an additional embodiment, the frame further comprises at least one connection portion coupled to at least one of the at least one superior arm and/or the at least one inferior arm, the at least one connection portion extending along a longitudinal axis of the frame and configured to receive a second portion of the fixed sample thereon. In yet an additional embodiment, the connection portion is configured to receive the second portion of the mammalian tissue thereon, and wherein the method further comprises the step of securing the second portion of the fixed sample to the frame using one or more sutures.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the tissue product comprises a valve having a bileaflet configuration or a trileaflet configuration. In another embodiment, the desired shape results in a valve having symmetrical leaflets. In yet another embodiment, the fixed sample is sized and shaped to substantially or completely similar to an outer perimeter of the frame. In an additional embodiment, the frame further comprises at least one vertical bar coupled to at least one of the at least one superior arm and/or the at least one inferior arm. In yet an additional embodiment, the frame further comprises at least one lower arm coupled to at least one of the at least connection portion and the at least one vertical arm.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the frame (or tissue product) is configured to move from a first, closed configuration to a second, open configuration. In an additional embodiment, when the frame is in the first, closed configuration, it is configured to fit within a mammalian luminal organ, such as by percutaneous delivery through the mammalian luminal organ. In yet an additional embodiment, the tissue product is configured as a stent valve. In another embodiment, the stent valve is configured for use as a venous valve. In yet another embodiment, the tissue product is configured so that the fluid native to the mammalian luminal organ can pass through an inlet portion of the tissue product and exit from an outlet portion of the tissue product

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the fixed sample coupled to the frame operates as a valve. In another embodiment, the fluid native to the mammalian luminal organ is at least partially prevented from flowing from the outlet portion to the inlet portion due to a configuration of the tissue product. In yet another embodiment, the fixed sample comprises mammalian pulmonary ligament. In an additional embodiment, the fixed sample comprises visceral pleura. In yet an additional embodiment, the fixed sample comprises tissue having stretchability and durability properties to allow the fixed sample to move relative to the fluid flow through the lumen defined within the tissue product.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the frame is capable of expansion using a balloon catheter. In an additional embodiment, the frame is autoexpandable. In yet an additional embodiment, the frame comprises a material selected from the group consisting of nitinol, chromium, cadmium, molybdenum, nickel, a nickel composite, nickel-cadmium nickel-chromium, nitinol palladium, palladium, cobalt, platinum, and stainless steel. In various embodiments, the fixed samples is configured as a products selected from the group consisting of a stent cover, a diaphragm cover, a hernia repair cover, a brain cover, a general organ cover, a wound cover, a prosthetic device cover, a skull cover, a general tissue cover, a tissue valve, a patch, a surgical membrane, a skin substitute, a suture reinforcement, a tubular structure, a tendon replacement, a bladder tissue replacement, a urethra tissue replacement, a vaginal tissue replacement, a muscle replacement, and another tissue replacement.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the positioning step is performed by positioning at least part of the fixed sample around the at least part of the frame. In another embodiment, the positioning step is performed by positioning at least part of the fixed sample around one or more of a superior arm, an inferior arm, and a connection portion of the frame. In yet another embodiment, the positioning step is performed by positioning at least part of the fixed sample around at least part of the frame so that at least part of the fixed sample operates as one or more valve leaflets.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the method further comprises the step of forming the fixed sample into a product configured for mammalian treatment or therapy. In an additional embodiment, the step of fixing the sample of pulmonary region tissue comprises fixing a sample of pulmonary ligament tissue, resulting in a fixed pulmonary ligament sample. In yet an additional embodiment, the step of fixing the sample of pulmonary region tissue comprises fixing a sample of visceral pleura tissue, resulting in a fixed visceral pleura sample.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the placing step is performed in connection with stretching the fixed sample in a first direction. In another embodiment, the placing step is performed in connection with stretching the fixed sample in a second direction different from the first direction. In yet another embodiment, the method further comprises the step of determining lengths of one or more fibers of the sample of pulmonary region tissue prior to, during, or after the fixing step. In an additional embodiment, the method further comprises the step of determining desmosine content of the sample of pulmonary region tissue prior to, during, or after the fixing step.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the acquiring step is performed to acquire the at least a portion of pulmonary region tissue from a mammalian heart/lung block. In another embodiment, the method further comprises the step of preseeding the sample of pulmonary region tissue to facilitate endothelialization prior to performing the fixing step. In yet another embodiment, wherein the fixed sample is between about 40 and about 300 microns in thickness. In an additional embodiment, the fixed sample comprises pulmonary ligament tissue having a thickness of between about 80 microns and about 120 microns, and even as high as about 300 microns. In yet an additional embodiment, the fixed sample comprises visceral pleura tissue having a thickness of between about 40 microns and about 80 microns.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the acquiring step is performed to acquire the at least a portion of a pulmonary region tissue from a middle-anterior portion of at least one lung of the mammal. In another embodiment, the acquiring step is performed to acquire the at least a portion of a pulmonary region tissue by making an incision in the at least one lung and pressing tissue of the at least one lung away from a visceral pleura. In yet another embodiment, the fixing step is performed using a fixative comprising a glutaraldehyde solution having a concentration of glutaraldehyde of less than 1%.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the method further comprising the step of storing the fixed sample in a storage solution. In another embodiment, fixative has a different fixative concentration than the storage solution. In yet another embodiment, the fixing step is performed using a fixative that is buffered. In an additional embodiment, the fixing step is performed using a fixative having a pH of between about 7.2 and about 7.6. In yet an additional embodiment, the fixing step is performed so that the sample of pulmonary region tissue contacts the fixative for at least about 24 hours.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the storage solution a glutaraldehyde solution having a concentration of glutaraldehyde of or about 0.5%. In another embodiment, the fixing step is performed within a tray lined with a silicone elastomer and by pinning the sample of pulmonary region tissue to the silicone elastomer. In yet another embodiment, the fixing step is performed using bovine serum albumin. In an additional embodiment, the method further comprises the step of removing the fixative from the fixed sample, and placing the fixed sample in a solution comprising at least one item selected from the group consisting of saline, a preservative, bovine serum albumin, and liquid nitrogen.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the method further comprises the step of decellularizing at least a portion of the sample of pulmonary region tissue prior to performing the fixing step. In an additional embodiment, the method further comprises the step of sterilizing the at least a portion of the sample of pulmonary region tissue prior to performing the fixing step. In an additional embodiment, method further comprises the step of sterilizing the fixed sample.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the method further comprises the step of treating a patient using the fixed sample. In an additional embodiment, the method further comprises the step of treating a patient using the product. In yet an additional embodiment, the fixed sample is acellular. In another embodiment, the product is configured for use in connection with transcatheter aortic-valve implantation. In yet another embodiment, the product is configured for percutaneous or surgical implantation.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the product is configured for use to replace a valve selected from the group consisting of an aortic valve, a mitral valve, a pulmonary valve, a tricuspid valve, and a percutaneous valve. In another embodiment, the fixed sample has a thickness that is smaller than a thickness of pulmonary tissue. In yet another embodiment, the product has an overall bulk that is smaller than a bulk of a corresponding product made using fixed pericardial tissue instead of using the fixed sample. In an additional embodiment, the fixed visceral pleura product contains at least one valve leaflet, wherein a non-mesothelial side of the fixed visceral pleura sample is on a relative front of the at least one valve leaflet, and wherein a mesothelial side of the fixed visceral pleura sample is on a relative back of the at least one leaflet.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the fixed sample has a circumferential axis corresponding to a circumferential axis of the at least a portion of pulmonary region tissue, wherein the fixed sample has an axial axis corresponding to an axial axis of the at least a portion of pulmonary region tissue. In an additional embodiment, the fixed sample can stretch in a direction of the circumferential axis of the fixed sample a first distance, and wherein the fixed sample can stretch in a direction of the axial axis of the fixed sample a second distance, the second distance being less than the first distance. In an additional embodiment, the method further comprises the step of forming the fixed sample into a product configured for mammalian treatment or therapy, wherein the fixed sample is oriented so that the circumferential axis of the fixed sample is aligned within an axial axis of the product, the axial axis being perpendicular to a circumferential axis of a luminal organ to receive the product.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the method comprises the steps of acquiring at least a portion of a pulmonary region tissue from a mammal, selecting a sample of pulmonary region tissue from the at least a portion of a pulmonary region tissue, and forming the sample of pulmonary region tissue into a tissue product configured for mammalian treatment or therapy. In another embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting a sample of pulmonary ligament tissue from the mammalian tissue. In yet another embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting a sample of visceral pleura tissue from the mammalian tissue.

In an exemplary embodiment of a processed tissue of the present disclosure, the processed tissue is obtained by acquiring at least a portion of a pulmonary region tissue from a mammal, selecting a sample of pulmonary region tissue from the at least a portion of a pulmonary region tissue, and fixing the sample of pulmonary region tissue using a fixative, resulting in a fixed sample.

In an exemplary embodiment of a processed pulmonary region tissue of the present disclosure, the pulmonary region tissue is obtained by fixing a sample of pulmonary region tissue using a fixative, the sample of pulmonary region tissue selected from a larger quantity of pulmonary region tissue harvested from a mammal. In an additional embodiment, the sample of pulmonary region tissue comprises pulmonary ligament. In yet an additional embodiment, the sample of pulmonary region tissue comprises visceral pleura.

In an exemplary embodiment of a processed pulmonary region tissue product of the present disclosure, the pulmonary region tissue product is obtained by forming a sample of pulmonary region tissue fixed using a fixative into a pulmonary region tissue product, the sample of pulmonary region tissue selected from a larger quantity of pulmonary region tissue harvested from a mammal, wherein the pulmonary region tissue product is configured for mammalian treatment or therapy. In another embodiment, the sample of pulmonary region tissue comprises pulmonary ligament. In yet another embodiment, the sample of pulmonary region tissue comprises visceral pleura.

In an exemplary embodiment of a product of the present disclosure, the product comprises a frame configured to retain a mammalian tissue thereon, and the mammalian tissue coupled to the frame, wherein when the product is positioned within a mammalian luminal organ, fluid native to the mammalian luminal organ may pass through a lumen defined within the product. In another embodiment, the frame comprises at least one superior arm and at least one inferior arm positioned at or near an inlet portion of the product, the at least one superior arm and the at least one inferior arm configured to receive a first portion of the mammalian tissue thereon. In yet another embodiment, the at least one superior arm and the at least one inferior arm is configured to receive the first portion of the mammalian tissue thereon and to retain said mammalian tissue using one or more sutures. In an additional embodiment, the frame further comprises at least one connection portion coupled to at least one of the at least one superior arm and/or the at least one inferior arm, the at least one connection portion extending along a longitudinal axis of the device and configured to receive a second portion of the mammalian tissue thereon.

In an exemplary embodiment of a product of the present disclosure, the connection portion is configured to receive the second portion of the mammalian tissue thereon and to retain said mammalian tissue using one or more sutures. In an additional embodiment, the product is configured as a bileaflet frame. In yet an additional embodiment, the product is configured as a trileaflet frame. In another embodiment, the mammalian tissue is sized and shaped to substantially or completely conform to an outer perimeter of the frame. In yet another embodiment, the frame further comprises at least one vertical bar coupled to at least one of the at least one superior arm and/or the at least one inferior arm.

In an exemplary embodiment of a product of the present disclosure, the frame further comprises at least one lower arm coupled to at least one of the at least connection portion and the at least one vertical arm. In another embodiment, the frame is configured to move from a first, closed configuration to a second, open configuration. In yet another embodiment, wherein when the frame is in the first, closed configuration, the product is configured for percutaneous passage through the mammalian luminal organ. In an additional embodiment, the product is configured as a stent valve. In yet an additional embodiment, the stent valve is configured for use as a venous valve.

In an exemplary embodiment of a product of the present disclosure, the fluid native to the mammalian luminal organ passes through an inlet portion of the product and exits from an outlet portion of the product when the product is positioned within the mammalian luminal organ. In an additional embodiment, the mammalian tissue coupled to the frame operates as a valve. In yet an additional embodiment, the fluid native to the mammalian luminal organ is at least partially prevented from flowing from the outlet portion to the inlet portion when the product is positioned within the mammalian luminal organ. In another embodiment, the mammalian tissue comprises mammalian pulmonary ligament. In yet another embodiment, the mammalian tissue comprises mammalian pulmonary viscera.

In an exemplary embodiment of a product of the present disclosure, the mammalian tissue comprises tissue having stretchability and durability properties to allow the mammalian tissue to move relative to fluid flow through the lumen defined within the product. In another embodiment, the mammalian tissue is fixed. In yet another embodiment, the mammalian tissue is fixed using glutaraldehyde. In an additional embodiment, the frame is capable of expansion using a balloon catheter. In yet an additional embodiment, the frame is autoexpandable.

In an exemplary embodiment of a product of the present disclosure, the frame comprises a material selected from the group consisting of nitinol, chromium, cadmium, molybdenum, nickel, a nickel composite, nickel-cadmium nickel-chromium, nitinol palladium, palladium, cobalt, platinum, and stainless steel.

In an exemplary embodiment of a method of the present disclosure, the method comprises the steps of shaping an mammalian tissue so that the mammalian tissue will fit around portions of a frame, the mammalian tissue excised from a mammalian body, positioning the mammalian tissue around a mount, positioning at least part of a frame around the mammalian tissue positioned around the mount, and connecting the mammalian tissue to the at least part of the frame to form the product. In another embodiment, the method further comprises the step of processing the excised mammalian tissue prior to the shaping step. In yet another embodiment, the processing step is performed by excising the mammalian tissue from the mammalian body, removing any undesirable portions of the excised mammalian tissue, placing the excised mammalian tissue on a frame, and fixing the tissue using a fixative. In an additional embodiment, the shaping step is performed by stretching the mammalian tissue and cutting the mammalian tissue to form a desired shape.

In an exemplary embodiment of a method of the present disclosure, the connection step is performed by positioning at least part of the mammalian tissue around the at least part of the frame. In another embodiment, the connection step is performed by positioning at least part of the mammalian tissue around one or more of a superior arm, an inferior arm, and a connection portion of the frame. In yet another embodiment, the connection step is further performed by suturing at least part of the mammalian tissue around the at least part of the frame. In an additional embodiment, the connection step is performed by positioning at least part of the mammalian tissue around the at least part of the frame so that at least part of the mammalian tissue operates as one or more valve leaflets. In yet an additional embodiment, the mammalian tissue comprises pulmonary ligament. In an exemplary embodiment of a method of the present disclosure, the mammalian tissue comprises visceral pleura.

In an exemplary embodiment of a method of processing a tissue of the present disclosure, the method comprises the steps of acquiring a sample of pulmonary region tissue from a mammal, and fixing the sample of pulmonary region tissue using a fixative, resulting in a fixed sample. In another embodiment, the step of acquiring a sample of pulmonary region tissue comprises selecting a sample of pulmonary ligament tissue from the mammal. In yet another embodiment, the step of selecting a sample of pulmonary region tissue comprises selecting a sample of visceral pleura tissue from the mammal.

In an exemplary embodiment of a processed pulmonary ligament of the present disclosure, the processed pulmonary ligament is prepared by fixing a sample of pulmonary region tissue acquired from a mammal using a fixative, resulting in a fixed sample.

In an exemplary embodiment of a method of the present disclosure, the method comprises the step of fixing a sample of pulmonary region tissue acquired from a mammal using a fixative, resulting in a fixed sample

In an exemplary embodiment of a method for preparing a tissue material of the present disclosure, the method comprises the step of decellularizing a segment of pulmonary region tissue. In another embodiment, the method further comprises the step of: sterilizing the pulmonary region tissue. In yet another embodiment, the method further comprises the step of fixing the pulmonary region tissue. In an additional embodiment, the pulmonary region tissue comprises pulmonary ligament tissue. In yet an additional embodiment, the pulmonary region tissue comprises visceral pleura tissue.

In an exemplary embodiment of a medical article of manufacture, the medical article of manufacture comprises acellular pulmonary region tissue sterilely enclosed within packaging. In another embodiment, the pulmonary region tissue is chemically fixed. In yet another embodiment, the pulmonary region tissue is not chemically fixed. In an additional embodiment, the pulmonary region tissue comprises pulmonary ligament tissue. In yet an additional embodiment, the pulmonary region tissue comprises visceral pleura tissue.

In an exemplary embodiment of a method for treating a patient of the present disclosure, the method comprises the step of introducing into a patient a medical device including pulmonary region tissue. In another embodiment, the tissue is acellular. In yet another embodiment, the pulmonary region tissue comprises pulmonary ligament tissue. In an additional embodiment, the pulmonary region tissue comprises visceral pleura tissue.

BRIEF DESCRIPTION OF THE DRAWINGS

The disclosed embodiments and other features, advantages, and disclosures contained herein, and the matter of attaining them, will become apparent and the present disclosure will be better understood by reference to the following description of various exemplary embodiments of the present disclosure taken in conjunction with the accompanying drawings, wherein:

FIGS. 1A and 1B show a swine pulmonary ligament connected to a lung, according to exemplary embodiments of the present disclosure;

FIG. 2A shows a close-up view of a swine pulmonary ligament, according to an exemplary embodiment of the present disclosure;

FIG. 2B shows a portion of a pulmonary ligament held in place upon a frame, according to an exemplary embodiment of the present disclosure;

FIGS. 3A and 3B show a fixed product, according to exemplary embodiments of the present disclosure;

FIGS. 4A-4D show various depictions of a portion of a pulmonary ligament, after fixation, formed into an exemplary constructed valve according to exemplary embodiments of the present disclosure;

FIGS. 5A-5D show various processed lung ligament products in various configurations, according to exemplary embodiments of the present disclosure;

FIG. 5E shows a block diagram of components of a kit, according to an exemplary embodiment of the present disclosure;

FIGS. 5F and 5G show mammalian tissue and tissue harvest locations, according to exemplary embodiments of the present disclosure;

FIGS. 6A and 6B show a bileaflet frame configuration, according to an exemplary embodiment of the present disclosure;

FIG. 7A shows a portion of a mammalian tissue cut/shaped to fit along a bileaflet frame, according to an exemplary embodiment of the present disclosure;

FIGS. 7B and 8A show how portions of mammalian tissue can be positioned within/around portions of a frame, according to exemplary embodiments of the present disclosure;

FIG. 8B shows an exemplary product having a bileaflet frame and a tissue positioned thereon, according to an exemplary embodiment of the present disclosure;

FIGS. 9A and 9B show a trileaflet frame configuration, according to an exemplary embodiment of the present disclosure;

FIG. 10A shows a portion of a mammalian tissue cut/shaped to fit along a trileaflet frame, according to an exemplary embodiment of the present disclosure;

FIG. 10B shows an exemplary product having a trileaflet frame and a tissue positioned thereon, according to an exemplary embodiment of the present disclosure;

FIG. 10C shows an exemplary product configured as a valve and positioned within a mammalian luminal organ, according to an exemplary embodiment of the present disclosure; and

FIG. 11 shows steps of a method to manufacture a product, according to an exemplary embodiment of the present disclosure.

An overview of the features, functions and/or configurations of the components depicted in the various figures will now be presented. It should be appreciated that not all of the features of the components of the figures are necessarily described. Some of these non-discussed features, such as various couplers, etc., as well as discussed features are inherent from the figures themselves. Other non-discussed features may be inherent in component geometry and/or configuration.

DETAILED DESCRIPTION

For the purposes of promoting an understanding of the principles of the present disclosure, reference will now be made to the embodiments illustrated in the drawings, and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of this disclosure is thereby intended.

The present disclosure contains disclosure of novel methods and uses for harvesting and applying certain mammalian tissue for use in connection with various medical applications. The mammalian pulmonary ligament and the mammalian visceral pleura, as referenced in detail below and disclosed within the present application, can be harvested, fixed, and used for a number of medical applications previously unknown and not identified in the medical arts. In at least one embodiment of the present disclosure, pulmonary ligament tissue is identified, harvested, fixed, and ultimately used in connection with mammalian treatment/therapy. As referenced herein, pulmonary ligament and visceral pleura are both “pulmonary region” tissue.

As referenced in detail herein, it is advantageous to identify and process thin scaffold biological tissue that consists of largely elastin and some collagen fibers (the converse of SIS), since elastin is not as prone to fixation as collagen fibers. Hence, fixation of tissue with elastin largely maintains its elasticity and hence biological mechanical activity. Furthermore, it is advantageous to identify a thin membraneous native tissue that does not require any processing, such as stripping of muscle or treatment with antibiotics given the bacteria flora such as present within the intestines. Finally, there is significant advantage to tissue that has epithelial layers on both sides of the tissue. As referenced in detail herein, the present disclosure includes uses and methods in connection with such a biological tissue and processing steps for various biological applications.

The visceral pleura that covers the lung extends to the hilum where it becomes continuous with the parietal pleura that covers the diaphragm, chest wall, and mediastinum. As the anterior and posterior pleural extend below the pulmonary veins, the two layers of pleura come together to form the inferior pulmonary ligament. Hence, the pulmonary ligament is a double layer of pleura that drapes caudally from the lung root and loosely tethers the medial aspect of the lower lobe of the lung to the mediastinum. However, and importantly, the pulmonary ligament does not functionally behave the same as two layers of pleura, as the non-isotropy of pulmonary ligament tissue is notably different than just two layers of pleura. Furthermore, the degree of collagen within pulmonary ligament is also different than in two layers of pleura, and the function of pulmonary ligament is also different, as pulmonary ligament tissue resists load in one direction. The pulmonary ligament tethers the lung and has substantial elasticity (over 200% extension, which may be a lateral extension) to expand with each inflation of the lung. The significant elasticity stems from the high elastin content. Contrary to collagen, elastin cannot be fixed and largely retains its elasticity post fixation. As such, and as described above and otherwise herein, the novel nature of identifying, harvesting, fixing, and using processed lung ligament tissue can result in numerous therapies and treatments not previously considered or used in the medical arts.

In certain embodiments of processed pulmonary ligament 50 and/or processed visceral pleura 60 of the present disclosure, said tissues can have a microarchitecture including non-randomly oriented collagen and elastin fibers, which can be retained from the native microarchitecture of the processed pulmonary ligament 50 and/or processed visceral pleura 60, and/or the processed pulmonary ligament 50 and/or processed visceral pleura 60 can exhibit an anisotropic elastic character, for example as can be demonstrated in biaxial stretch testing and/or through optical and/or microscopic visualization of the tissue microstructure. As well, in these and other embodiments, processed pulmonary ligament 50 tissue can have a thickness of about 80 microns to about 100 or 120 microns, and even as high as about 300 microns, including thicknesses between about 90 microns and 100 microns, which depends upon the species from which the pulmonary ligament tissue is obtained. Processed visceral pleura 60 may have a smaller thickness, such as between about 40 microns and about 80 microns, as referenced further herein. Other embodiments of processed pulmonary ligament 50 and/or processed visceral pleura 60 of the present disclosure may be up to 300 microns in thickness. In an actual exemplary sample of 15 harvested processed pulmonary ligament samples obtained according to the present disclosure, the average thickness was 102 microns, and the thickness range was from 22 microns to 269 microns. Different thicknesses of tissue may be preferred for different embodiments, such as relatively thinner tissues for valve applications, and relatively thicker tissues for hernia repair, for example.

For various pulmonary ligament 30 and/or visceral pleura 556 samples, a predominant proportion of the collagen fibers in the tissue are oriented generally in a first direction, with that direction having extended substantially parallel to the median (or midsagittal) plane of the animal from which the tissue was harvested. For example, and in at least one embodiment, at least 75% of collagen fibers within the harvested pulmonary ligament 30 and/or visceral pleura 556 tissue are oriented in a first direction. In at least another embodiment, at least 60% of collagen fibers within the harvested pulmonary ligament 30 and/or visceral pleura 556 tissue are oriented in a first direction. Furthermore, and in various pulmonary ligament 30 and/or visceral pleura 556 samples, said tissues include elastin fibers that extend in a direction transverse to that of the predominating collagen fibers contained therein.

FIGS. 1A and 1B pictorially show a swine pulmonary ligament (an exemplary ligament 30) by way of gripping a portion of the pig (such as by the aorta and/or esophagus (collectively shown as 32 in FIG. 1A) or tissue in that general vicinity) and pulling the same away from the lung 34, as shown in FIG. 1B. Gripping and/or separation of tissue can be performed by hand, as shown in FIG. 1A, and/or by using forceps 40, as shown in FIG. 1B. The pulmonary ligament 30 is clearly shown and identified in FIGS. 1A and B.

FIG. 2A shows a closer view of a portion of the pulmonary ligament 30, and FIG. 2B shows a portion of the pulmonary ligament 30 held in place using a series of clamps 42 positioned around a mount 44, for example, and being fixed with a fixative, such as glutaraldehyde. Post fixation pulmonary ligament (which could also be referred to as a processed ligament 50 of the present disclosure, potentially configured as an exemplary product 100 of the present disclosure as referenced below), as shown in FIGS. 3A and 3B, has high elasticity, and both sides of the ligament tissue are smooth and covered with an epithelial layer that secretes a lubricant.

FIGS. 4A-4D show various depictions of a portion of a porcine pulmonary ligament 30, after glutaraldehyde fixation (to form processed ligament 50 and potentially an exemplary product 100), and formed into an exemplary constructed valve 400 of the present disclosure. For example, and as shown in FIGS. 2B and 4A-4C, pulmonary ligament 30 can be placed upon a mount 44, using one or more forceps 40 and/or clamps 42 (as shown in FIG. 2B), and/or one or more sutures 800 (as shown in FIG. 4B in connection with use of a mount 44, and as described in further detail herein in connection with one or more frames 600 of the present disclosure). Placement may also include folding portions of pulmonary ligament 30 around portions of mount 44, as shown by way of folded portion 48 in FIG. 4C. If one or more sutures 800 are used, said sutures 800 could comprise nylon or another suitable material, and could be placed using a needle (not shown), as described in further detail herein.

As shown in the various figures, the valve 400 (comprising pulmonary ligament in the embodiment shown), which is an exemplary processed product 100 of the present disclosure, easily flexes and maintains its shape. Products 100 can include processed ligament 50 or processed visceral pleura 60, as referenced in further detail herein, and may also be referred to herein as medical articles of manufacture. As referenced herein, pulmonary ligament 30 refers to pulmonary ligament tissue that has not yet been processed, and processed ligament 50, optionally configured as one or more processed products 100 of the present disclosure, refers to tissue that has been processed, such as by fixation, and optionally configured as products 100. Similarly, and as also referenced herein, visceral pleura 556 refers to visceral pleura tissue that has not yet been processed, and processed visceral pleura 60, optionally configured as one or more processed products 100 of the present disclosure, refers to tissue that has been processed, such as by fixation, and optionally configured as products 100. Various valves 400 of the present disclosure may comprises any number of valves, including, but not limited to, aortic valves, mitral valves, pulmonary valves, tricuspid valves, and/or other percutaneous valves.

FIGS. 5A-5D show various processed products 100 in various configurations, according to exemplary embodiments of the present disclosure. For example, FIG. 5A shows an exemplary product 100 of the present disclosure configured as a patch, membrane, tissue replacement, cover, or reinforcement. Said embodiments (patch, membrane, tissue replacement, cover, or reinforcement) shall be referred to generally as patches 500, as labeled in FIG. 5A. FIG. 5B shows another exemplary product 100 of the present disclosure configured as a curved patch, membrane, tissue replacement, cover, or reinforcement (collectively curved patches 500). FIG. 5C shows an exemplary product 100 configured as a tube 502, and FIG. 5D shows an exemplary product 100 configured as a valve 400. Valve 400, as shown in FIG. 5D, is configured as a tri-leaflet valve 400 (including, for example, leaflets 802, 804, and 1000, as referenced in further detail herein), but other valve 400 embodiments of the present disclosure may be single leaflet valves 400, bileaflet valves 400, or valves 400 with more than three leaflets. In each embodiment shown therein, products 100 comprise one or more processed ligaments 50 and/or one or more processed visceral pleura 60.

Other product 100 configurations are contemplated by the present disclosure, as various biological uses of products 100 can be had, and the present disclosure is not limited to the configurations shown in the figures. For example, a venous stent cover (an exemplary cover 502) with a membrane and valve 400 included is an exemplary product 100 of the present disclosure, with features shown in one or more figures referenced herein, such as FIGS. 5B, 5C, and 5D. For example, a product 100 of the present disclosure could have an external shape shown in FIG. 5C and a valve 400 as shown in FIG. 5D.

As for preparation of all or a portion of a pulmonary ligament 30 or a visceral pleura 556, it is known that biological tissues are pre-stretched or otherwise pre-stressed in vivo for optimal function. For an exemplary embodiment of this particular tissue, the degree of pre-stretch was determined, in at least one method, by measuring the dimensions of the tissue before and after harvest. This was accomplished in this particular example by placing various dots/markings (such as dots/markings 575 shown in FIG. 5F) on the ligament 30 and/or visceral pleura 556 itself in its in vivo state to determine the degree of stretch in the two principle directions (referred to herein as the x and y directions). Using such a method, one can characterize that the tissue shrinks by X and Y amount in the x and y directions.

In the glutaraldehyde (or other chemical/mechanism) fixation and mounting process of the tissue on mounts 44 or frames (for stents and other uses as referenced herein), the tissue can be pre-stretched by X and Y to the in vivo values to ensure optimal function of the tissue. In addition, fiber lengths and/or desmosine contents could be measured/obtained in connection with various steps of fixation, including but not limited to determining an amount of tissue shrinkage due to fixation. For example, a stress-strain relation could be determined in fresh lung ligament 30 tissue and processed lung ligament 50 tissue, and a fixed strain could be selected that corresponds to the stress in fresh tissue, for example. Similar stress-strain relations could also be determined in fresh visceral pleura 556 tissue and processed visceral pleura 60 tissue. Furthermore, optical means of selection, such as with the use of traditional light, polarized light, and/or other light, with and without magnification, could be used to optically scan the various harvested tissues.

An example pulmonary ligament 30 and/or visceral pleura 556 harvesting procedure is described as follows. In at least one method, the heart/lung block can be extracted from a mammal (such as in connection with a meat processing facility), and the extracted tissue could then be placed in a relatively cold saline solution to help preserve the same. The heart/lung block may be generally referred to herein a pulmonary region tissue, which may include, but is not limited to, lung tissue and one or more of the bronchi, pulmonary artery, pulmonary vein, and/or the heart, so long as the desired tissue to be harvested (pulmonary ligament 30 and/or visceral pleura 556) is contained therein. At or before the time of processing, the tissue can be inspected for blood infiltration, fatty material, perforations, and/or other irregularities, and portions of the tissue containing the same can be treated to either removed the undesired components or discarded/disregarded in view of other portions of the tissue that are relatively homogenous and free of undesired properties, such as perforations or fat.

After selection of desired portions of pulmonary ligament 30 and/or visceral pleura 556 from the overall resected tissue, the selected membranes can be mounted in mounts 44 (such as available circular or rectangular frame mounts) to prevent shrinkage and/or folding during fixation, and can be submerged in a fixation solution (such as glutaraldehyde, for example) for fixation. Prior to mounting and/or fixation, or after mounting and/or fixation if desired, the pulmonary ligament 30 and/or visceral pleura 556 can be pre-seeded to make it more likely to endothelialize. As pulmonary ligament tissue has mesothelium on both sides and visceral pleura has mesothelium on only one side, pre-seeding (also referred to as endothelial seeding) could be performed on the non-mesothalial side of the tissue. After fixation, a relatively flat piece of fixed tissue will result. Using another method, and after selection of the membranes or desired portions thereof, the membranes can be placed on multidimensional molds, for example, allowing the user to stretch and/or otherwise fit the membrane so to mimic the mold shape, and then fix the membrane on the mold. With such a method, the resultant fixed material will maintain or closely resemble to multidimensional shape of the mold, and can be used for various purposes.

Various sizes and/or thicknesses of processed lung ligament 50 and/or processed visceral pleura 60 tissues could be used and be tailored to specific applications. For example, and in embodiments of processed lung ligament 50 and/or processed visceral pleura 60 tissue ultimately used as valves 400 (exemplary products 100 of the present disclosure), lung ligament 50 tissue of between about 80 microns and about 100 microns to about 300 microns could be used, while visceral pleura 60 between about 40 microns and about 80 microns could be used.

With respect to initial tissue harvesting of visceral pleura 556 tissue, an exemplary method of the present disclosure includes the step of isolating tissue 556 from the middle-anterior portion of the lungs, 34 which tends to be relatively thicker and more uniform than other portions of the lung 34. A lateral incision can be made, and using forceps 40 for example, the lung 34 tissue can be carefully pressed away from the visceral pleura 556. FIG. 5F shows a diagram of a portion of a mammalian body 550 showing the lungs 34 and an identified harvest section 552, generally comprising the middle-anterior portion of the lungs 34. Two portions of tissue are shown, namely the parietal pleura 554 that lines the chest cavity and the visceral pleura 556 which lines the lungs 34 and is internal to the parietal pleura 554. As shown in FIG. 5F, and referenced in further detail herein the mesothelial side 860 of visceral pleura 556 is on a relative outside of the lung 34, while the non-mesothelial side 862 of visceral pleura 556 is on the relative inside of the lung 34. Pulmonary region tissue 558 is also shown therein, which may include, but is not limited to, lung tissue and one or more of the bronchi, pulmonary artery, pulmonary vein, and/or the heart, as previously referenced herein. The acquired pulmonary ligament 30 and/or visceral pleura 556 from said pulmonary region tissue may be referred to herein as “samples” of tissue from the pulmonary region tissue 558. After an initial portion of visceral pleura 556 tissue (such as ˜0.5 cm or so) has been separated, the tissue can be gently worked away (manually using one's hand/fingers, for example), taking care/precautions not to overly stress or pull on the visceral pleura 556 tissue. Prior to removal of the visceral pleura 556, the general orientation can be noted and potentially marked on the tissue, noting that visceral pleura 556 has different degrees of potential stretch depending on orientation.

FIG. 5F also demonstrates an exemplary harvesting method whereby pulmonary ligament 30 and/or visceral pleura 556 tissue is harvested and ultimately used in a desired orientation based upon an orientation of harvest. As shown in FIG. 5F, the x-axis (identified as “X” in the figure) may also be referred to herein as a “circumferential” or “transverse” axis or direction/orientation of tissue, and the y-axis (identified as “Y” in the figure) may also be referred to herein as a “vertical” or “axial” axis or direction/orientation of tissue. Natural lung expansion and contraction, consistent with breathing, occurs in a fashion whereby pulmonary ligament 30 and/or visceral pleura 556 would stretch more in the circumferential direction as compared to the axial direction, so whereby pulmonary ligament 30 and/or visceral pleura 556 tissue harvested from a mammal would also have more stretchability in the circumferential direction as compared to the axial direction. Phrased differently, the axial direction is notably stiffer than the circumferential direction, which is also referred to herein as being relatively softer than movement/stretch in the axial direction. To leverage the inherent non-isotropy of said tissue(s), and using a specific orientation of the same in connection with one or more products 100 of the present disclosure, including but not limited to valves 400 as referenced herein, the tissue orientation would be identified at the time of harvest and use accordingly in connection with one or more products 100 of the present disclosure. For example, processed pulmonary ligament 50 and/or processed visceral pleura 60 can be oriented on frame 600, as referenced in further detail herein, so that the axial direction of the product 100 in a mammalian luminal organ (such as a blood vessel) is softer than the circumferential/radial direction, in reference to the product 100, as the circumferential direction is, for example, constrained by the diameter of the blood vessel and cannot distend further, while the axial direction is the direction of opening and closing a valve 400 (in a product 100 embodiment configured as a valve), where more deformation would be needed or desired. Leveraging this non-isotropy (directionality) could be used in connection with various products 100 of the present disclosure depending on the application of interest.

With respect to initial tissue harvesting of pulmonary ligament 30 tissue, an exemplary method of the present disclosure includes the step of isolating tissue 30 from the relative middle section between the lungs 34, as indicated by harvest sections 552 shown in FIG. 5G. The specific harvest section 552 used may depend on mammalian species, the age of the mammal, and/or the thickness of tissue required for a particular application. As with visceral pleura 556 (referenced above and shown in FIG. 5F), pulmonary ligament 30 thickness varies with location within the body. As generally referenced herein, efforts to avoid vascular areas (and/or those areas with blood infiltration), fatty material, perforations, and/or other irregularities should be made to that desirable pulmonary ligament 30 or visceral pleura 556 can be obtained. In addition, and regarding certain pulmonary ligament 30 or visceral pleura 556 tissue, avoiding said tissues near the lungs 34 and/or the aorta/esophagus 32 may also lead to preferable pulmonary ligament 30 or visceral pleura 556 harvest. Similar to visceral pleura 556 harvest, and prior to removal of the pulmonary ligament 30, the general orientation can be noted and potentially marked on the tissue, noting that pulmonary ligament 30 has different degrees of potential stretch depending on orientation, noting that as shown in FIG. 5G, ligament 30 is most elastic in the x-direction as shown in the figure.

Pulmonary ligament 30, as referenced herein, may be generally described as a sheet of tissue, and not generally as a combined/bundled tissue. For example, and upon pulmonary ligament 30 harvest, the sections of pulmonary ligament 30 suitable for harvest are generally continuous with the aorta, and are generally not part of the bundled ligament that descends from the mammalian lung root.

General tissue harvesting can apply to several mammalian species, including, but not limited to, cattle, pigs, and horses, such as from blocks of tissue collected after animal slaughter. Harvesting is preferred using clean/sterile conditions, and can proceed after an initial inspection of the blocks of tissue for portions of suitable tissue not having any malformations, abnormalities, perforations, tears, calcifications, spots, etc., as generally referenced herein. The desired tissue (pulmonary ligament 30 or visceral pleura 556) can be cleaned using a suitable solution (water and/or saline, for example), and fat and/or muscle covering the tissue can be removed, such as with the use of forceps 40. The removed tissue (pulmonary ligament 30 or visceral pleura 556) can be positioned about a mount 44, as described and shown herein, and attached to the same using clamps 42 and/or sutures, such as those comprising Nylon 0, used as overcast stiches, with a needle such as a 333/5 needle. The attachment step can be performed outside of a solution or within a solution, such as a fixative solution. One such fixative solution may comprise 0.65% glutaraldehyde solution BLUE. The dissected tissue can then be stored, upon the mount 44, within an appropriate fixative solution for an appropriate amount of time. For example, and to accomplish initial fixation, the tissue can be fixed in the fixative solution for at or approximately 24 hours, and the solution can be changed (to either the same fresh fixative solution or to another solution) and stored until the tissues are ready to be cut, formed, manipulated, or otherwise used. Keeping the tissue hydrated is important, as should the tissue completely or partially dry out, it would likely irretrievably lose desired mechanical properties. Long term (or relatively long term) storage can be in, for example, 0.65% glutaraldehyde solution BLUE or another solution for an initial period of time, and then changed to a lower concentration solution (such as 0.50% glutaraldehyde solution CELESTE), for example, and stored until needed.

Regarding fixation, an exemplary fixative solution of the present disclosure can be prepared, resulting in a buffered glutaraldehyde solution, can be prepared as follows. In at least one example of a fixative solution, and in less than 1 L of DDH₂O), the following can be added: 1) 2.05 h of NaOH, 2) 9.08 g of PO₄H₂K, and 3) 13 mL of 50% glutaraldehyde solution (or 26 mL of 25% glutaraldehyde solution). The desired pH would be at or near 7.4 for this exemplary fixative solution, and if the combined solution is not at 7.4, it can be adjusted using additional NaOH solution. After pH adjustment to the desired pH, the overall volume of the flask can be increased to 1.0 L, resulting in the exemplary fixative solution. Other fixative solutions may be optimal for use in connection with various fixation procedures of the present disclosure.

To ultimately fix acquired pulmonary ligament 30 or visceral pleura 556 tissue, at least one fixation method comprises fixing the pulmonary ligament 30 or visceral pleura 556 in a fixation solution for at least 24 hours, and optionally at a reduced temperature (such as at or near 23° C.). Other fixation times and temperatures may be used as well. For long-term storage of fixed tissue, storage in 0.5% glutaraldehyde (for example) can protect the fixed tissue. In at least one embodiment, fixation with minimal to no preload is recommended, as preloading may change the mechanical properties of the tissue during and/or after fixation. To maintain preferred tissue fiber orientation, flat or relatively-flat fixation would be recommended. Flat or relatively-flat fixation can be performed, for example, using a tray lied with a silicone elastomer (such as Sylgard), allowing for the tissue to remain flat or relatively flat when pinned down during the fixation process.

Regarding fixation, glutaraldehyde is widely used, and can be used in connection with various buffers, such as HEPES and phosphate buffers. In at least one method, glutaraldehyde is used around a neutral and slightly alkaline pH at or about 7.4, noting that other pH values or ranges can be used with various fixation methods. For example, and in at least one additional fixation method, formaldehyde (formalin) may be used, and/or glycerol may be used. In an exemplary fixation method using glycerol, at or about 98% glycerol may be used to fix the tissue. In at least one embodiment of a method of fixing pulmonary ligament 30 or visceral pleura 556 tissue, bovine serum albumin (BSA) can be used to remove cytotoxicity in connection with fixation, such as fixation using glutaraldehyde and/or formaldehyde. Eliminating glutaraldehyde and/or formaldehyde from the storage solution may be beneficial as such compositions are quite cytotoxic, and storage of fixed tissue in non-toxic solutions or using dry tissue technologies can be useful to stored said fixed tissue for various amounts of time.

Other fixation methods may include, but are not limited to, various cryo-preservation or dry tissue fixation methods known are developed in the art for tissue fixation. Furthermore, fixation could be performed at various loads or strains, such as in vivo stretch ratios, as determined by the markers (dots placed upon the tissue prior to harvest). For example, and as referenced above and at the time of or prior to harvest, markings could be placed on the lung ligament 30 or visceral pleura 556 tissue (using a marker, for example), and measurements between markings could provide the harvester with information relating to said tissue at a natural (non-stretched state). When placing said harvested tissue upon a frame for fixation, for example, said tissue could be stretched at various degrees of stretch, with either raw distance stretch being known and/or a percentage stretch being known based upon the distance between markings at the natural (non-stretched) and stretched states.

With respect to overall pulmonary ligament 30 and/or visceral pleura 556 preparation, preservation of the tissue's elastin component is important so that the intended uses of the prepared pulmonary ligament 50 and/or processed visceral pleura 60 may still be considered. As the overall flexibility of the processed pulmonary ligament 50 and/or processed visceral pleura 60 preparation is important for various uses, efforts to preserve the elastin component may be reflected in the overall preparation methods. Different methods may be used to generate different products 100 of the present disclosure, such as different frames, tissue stretching, fixation duration, and/or a combination of the same. Furthermore, decellularization of the epithelial layer or layers of pulmonary ligament 30, for example, can be performed while also preserving/keeping the elastin scaffolds. As is known, the biologically occurring pulmonary ligament includes a layer of mesothelial cells (a specialized type of epithelial cells) on each side of the ligament. In addition, storage can be had using saline and/or an additional preservative, so that the product 100 is safe to use when needed.

Pulmonary ligaments 30 and/or visceral pleura 556, for potential use in connection with the present disclosure, can be harvested from any number of mammalian species and used in the same or other species. For example, pulmonary ligaments 30 and/or visceral pleura 556 can be harvested from pigs, horses, cows, goats, sheep, etc., and used to treat the same species or different species, including humans. Further, pulmonary ligaments 30 and/or visceral pleura 556 could be harvested from one human and used to treat another human. For long or short term storage, for example, pulmonary ligaments 30 and/or visceral pleura 556 (and/or processed ligament 50, processed visceral pleura 60, and/or products 100 of the present disclosure) may be preserved by freezing in liquid nitrogen (−198° C. in at least one example). So to ensure that fixed tissue thickness, stiffness, strength, and/or micro-structure do not change (or substantially change) over time, various short- and/or long-term storage mechanisms may be used.

In at least one embodiment of a method of preparing fixed/processed lung ligament 30 and/or visceral pleura 556 tissue of the present disclosure, the method includes the steps of obtaining a heart/lung block (such as from a slaughterhouse), placing the heart/lung block in cold saline (or another suitable solution at various temperatures) for transport as needed, isolating the lung ligament 30 and/or visceral pleura 556 tissue, and fixing the same as referenced herein. Such a method may be performed while taking precautions/steps to avoid tissue, perforations, fenestrations, and/or blood vessels or infiltrations therein.

In at least one embodiment of a product of the present disclosure, the product is not treated with a fixative. Instead, the product, in at least one embodiment, is harvested from a mammal and used in connection with one or more procedures or as one or more products reference herein without the use of a fixative. In certain aspects, such non-fixed pulmonary ligament products can be acellular, e.g., after treatment with one or more decellularization agents, and/or sterile.

In additional embodiments, provided are medical articles (exemplary products 100), such as kits 525, shown in block diagram form in FIG. 5E, that may include processed pulmonary ligament 50, processed visceral pleura 60 tissue, and/or a product 100, sterilely enclosed within packaging 530. A sterile condition of pulmonary ligament 50, processed visceral pleura 60 tissue, and/or a product 100 within the packaging 525 may be achieved, for example, by terminal sterilization using irradiation, ethylene oxide gas, or any other suitable sterilization technique, and the materials and other properties of the medical packaging can be selected accordingly.

Uses of a processed pulmonary ligament 50 and/or processed visceral pleura 60, as referenced above, include, but are not limited to, the following applications:

a. As a cover for various stents, such for as coronary stents, peripheral stents (porto cava shunts), aortic stents, neurological stents, esophageal stents, biliary tract stents, and the like.

b. As various types of biological tissue valves, including, but not limited to, venous and/or arterial valves, which may have various leaflet configurations, such as monocusp, bileaflet, trileaflet, and others.

c. As a cover for saphenous vein bypasses, thus avoiding vein over-distension.

d. As a patch, in various cardiac and other surgical procedures, such as ventricular reconstruction, an arterial patch, a venous patch (such as a carotid endarterectomy), or to repair other holes.

e. As a placement around the ascending aorta after surgery to avoid aortic aneurysm formation in hypertensive patients.

f. As a membrane in cardiac, thoracic, or general surgery to avoid adhesion in reoperations (valvular, transplants, left ventricular assist device (LVAD), coronary artery bypass graft (CABG), pediatric surgery, or general surgery).

g. As a cover for LVAD diaphragms or a total artificial heart diaphragm.

h. As a cover for the synthetic net in hernia repair and abdominal dehiscense.

i. As a biologic skin substitute in burn patients avoiding infection and loss of proteins, water.

j. As a cover for organs such as the heart (to limit dilation of the left ventricle, for example), stomach, urinary bladder, and to avoid overdistension and/or to prevent adhesion especially in laparoscopic procedures of diabetic patients.

k. As a reinforcement of a suture line, such as with ventricular aneurysm repair, bariatric surgery, and fistulae repair for intestines, bronchus, and esophagus.

l. As a structure for biological composite tubes, such as stented or stentless valves for inclusion within a biological tube, which can be used, for example, in ascending aortic aneurysm (AAA) replacement or pulmonary artery replacement.

m. In orthopedic surgery, such as with tendon replacement (having advantages in resistance and elasticity), total or partial replacement of the articular capsulae during surgery of the hip, elbow, knee, and/or the like, and/or as a cover for various orthopedic prosthetic devices.

n. As a cover for neurosurgical applications, such as a cover of part of the brain surface during tumor resection or resection of the skull.

o. In urologic surgery, such as in connection with reconstruction of a partial or total urinary bladder and/or urethral resection.

p. In gynecological surgery, such as in connection with vaginal reconstruction after tumor resection or other trauma, with reconstruction of perineal muscles to fix the urinary bladder, or with uterus prolapse.

q. In head & neck surgery, such as in connection with reconstructive surgery, replacement of muscles (requiring elasticity and resistance), and as a cover for a maxillary prosthesis.

r. In connection with other trauma, such as treating vehicular accident victims by covering complex wounds until surgical repair, which may be complex, can take place.

In view of the various uses of processed pulmonary ligament 50 and/or processed visceral pleura 60 to create various products 100 of the present disclosure, said ligament 50 and/or visceral pleura 60 may be used to produce products 100 configured as stents and/or stent valves 400 as follows. FIGS. 6A and 6B show closed and opened stent valve frames, respectively, for use with various products 100 of the present disclosure. As shown in FIGS. 6A and 6B, an exemplary product 100 of the present disclosure comprises a frame 600, with said frames 600, in various embodiments, comprising at least one superior arm 602 and at least one inferior arm 604. Arms 602, 604, as shown in FIGS. 6A and 6B, may be positioned at or near a relative end of frame 600, and may be parallel or substantially parallel to one another. Frames 600, as shown in FIGS. 6A and 6B, further comprise a connection portion 606, and optionally one or more vertical bars 608 extending along an elongate axis (A-A′ as shown therein) to provide additional overall stability. As shown in FIG. 6B, an exemplary frame 600 comprises three vertical bars 608 extending along axis A-A′ along a portion of a length of frame 600 from a first end 610 to a second end 612.

At or near the relative second end 612 of frame 600, one or more lower arms 614 may be present, which may, as shown in FIG. 6B, connect to one or more vertical bars 608 and/or one or more elements of connection portion 606. A combination of vertical bars 608, as referenced in further detail below, may comprise a connection portion 606. Frames 600, or portions thereof, may comprise a number of biologically-compatible materials including, but not limited to, nitinol, chromium, cadmium, molybdenum, nickel, a nickel composite (such as, for example, nickel-cadmium and/or nickel-chromium), nitinol palladium, palladium, cobalt, platinum, and/or stainless steel.

Connection portion 606 is shown in FIG. 6B as being an element of an exemplary frame 600 coupling to one or more of superior arm(s) 602, inferior arm(s) 604, vertical bar(s) 608, and lower arm(s) 614. In at least one embodiment, and as shown in FIG. 6B, connection portion 606 comprises a plurality of connection bars 616, which are used to connect one or more processed ligaments 50 and/or visceral pleura 60, or one or more other bodily tissues having the necessary stretchability and durability properties necessary to be useful in connection with one or more products 100 of the present disclosure, to frame 600 as referenced in further detail herein. As referenced herein, a “tissue” may be referred to as a ligament 50 and/or visceral pleura 60, and ligament 50 and/or visceral pleura 60, in at least one embodiment, may comprise another non-ligament tissue having the necessary properties noted above.

As noted above, a plurality of vertical bars 608 may also comprise a connection portion 606 of the present disclosure. Therefore, and depending on how portions of frame 600 are viewed, the exemplary frame shown in FIGS. 6A and 6B may comprise one connection portion 606 and a plurality of vertical bars 606, or they may comprise two connection portions 606, with one connection portion 606 comprising connection bars 616 and the other connection portion 606 comprising vertical bars 608. In addition, and as shown in FIG. 6B, various frames 600 of the present disclosure may comprise one or more barbs 618 positioned along various portions of frames 600 (such as vertical bars 608, connection bars 616, and/or other components) to facilitate securing a product 100 within a mammalian luminal organ (to prevent migration), and/or to facilitate securing the tissue (such as ligament 50 and/or visceral pleura 60) to frame 600.

FIG. 7A shows an exemplary processed ligament 50 and/or visceral pleura 60 of the present disclosure molded for use with or as a bileaflet valve 400. As shown in FIGS. 6A and 6B, frame 600 is configured as two leaves with one connection portion 606. As referenced further herein, other frame 600 embodiments, such as being configured as a trileaflet valve 400 and as potentially a valve 400 with even more leaflets, may be produced consistent with the present disclosure. The processed ligament 50 and/or visceral pleura 60, as shown in FIG. 7A, is shaped substantially similar to an outer perimeter of frame 600 shown in FIGS. 6A and 6B. The shape shown in FIG. 7A represents processed ligament 50 and/or visceral pleura 60 configured so to create symmetrical valve leaflets upon placement of processed ligament 50 and/or visceral pleura 60 upon frame 600.

FIG. 7B shows a cross-section of a portion of an exemplary product 100 of the present disclosure, whereby individual connection bars 616 of an exemplary frame 600 are shown with a portion of a processed ligament 50 and/or visceral pleura 60 positioned therebetween. This view may be considered as an upper or lower cross-sectional view, and demonstrates an exemplary method of positioning a portion of processed ligament 50 and/or visceral pleura 60 within said connection bars 616 to secure the processed ligament 50 and/or visceral pleura 60 at that particular location within device 100.

FIG. 8A shows another cross-section of a portion of an exemplary product 100 of the present disclosure, whereby a superior arm 602 and an inferior arm 604 of an exemplary frame 600 are shown with a portion of a processed ligament 50 and/or visceral pleura 60 positioned therebetween. This view shows an exemplary method of positioning a portion of processed ligament 50 and/or visceral pleura 60 within said arms 602, 604 to secure the processed ligament 50 and/or visceral pleura 60 at that particular location within device 100. One or more sutures 800, as shown in FIG. 8A, may be used to connect two portions of processed ligament 50 and/or visceral pleura 60 to one another to prevent movement of the same. For example, and as shown therein, an end portion of processed ligament 50 and/or visceral pleura 60 may be positioned upon or adjacent to inferior arm 604, and wrapped counter-clockwise (as shown in FIG. 8A) around inferior arm 604. When the wrapped portion of processed ligament 50 and/or visceral pleura 60 is positioned near the end portion, it may continue being wrapped around frame 600 by way of wrapping clockwise (as shown in FIG. 8A) around superior arm 602, and the processed ligament 50 and/or visceral pleura 60 may be sutured to itself as shown in the figure.

An exemplary embodiment of a product 100 of the present disclosure comprising a frame 600 and processed ligament 50 and/or visceral pleura 60 attached thereto is shown in FIG. 8B. Product 100 is shown in a closed configuration in FIG. 8B, whereby processed ligament 50 and/or visceral pleura 60 is sutured to itself and/or to portions of frame 600 at multiple locations to hold the processed ligament 50 and/or visceral pleura 60 in place. As shown in FIG. 8B, product 100 is configured as a bileaflet valve 400, which may be used, for example, as a venous valve or another type of valve. Leaflets 802 and 804 are identified in FIG. 8B. In various embodiments referenced herein, processed ligament 50 and/or visceral pleura 60 is sutured to frame 600, but sutures 800 are outside of the bloodstream (are not in contact with blood flow) when frame 600 with processed ligament 50 and/or visceral pleura 60 thereon (an exemplary product 100) is positioned within a mammalian luminal organ having blood flowing therethrough.

A completed product 100 (such as shown in FIG. 8B and in FIG. 10B described below) may be configured as a stent or stent valve 400. Configurations as a stent valve 400 would utilize leaflets 802 and 804 to control the flow of fluid through a lumen 806 defined within product 100. The direction of fluid flow of such an embodiment would be such that fluid would enter inlet portion 808 of product 100 and exit from outlet portion 810 of product 100, as shown in FIG. 8B. In such a configuration, product 100 could be positioned within a mammalian luminal organ, and fluid flow through said organ could continue through lumen 806 of product 100.

FIGS. 9A and 9B show additional exemplary closed and opened stent valve frames, respectively, for use with various products 100 of the present disclosure. As shown in FIGS. 9A and 9B, an exemplary product 100 of the present disclosure comprises a frame 600 configured for ultimate use as a trileaflet valve 400, with said frames 600, in various embodiments, comprising at least one superior arm 602 and at least one inferior arm 604. Arms 602, 604, as shown in FIGS. 9A and 9B, may be positioned at or near a relative end of frame 600. Frames 600, as shown in FIGS. 9A and 6B, further comprise two or more connection portions 606 (as referenced in further detail below), and optionally one or more vertical bars 608 extending along an elongate axis to provide additional overall stability. As shown in FIG. 9B, such an exemplary frame comprises three vertical bars 608 extending along a portion of a length of frame 600 from a first end 610 to a second end 612. At or near the relative second end 612 of frame 600, one or more lower arms 614 may be present, which may, as shown in FIG. 6B, connect to one or more vertical bars 608 and/or one or more elements of connection portion 606. A combination of vertical bars 608, as referenced herein, may comprise a connection portion 606.

Depending on how portions of frame 600 are viewed, the exemplary frame 600 shown in FIGS. 9A and 9B may comprise two connection portions 606 and a plurality of vertical bars 608, or they may comprise three connection portions 606, with two connection portions 606 comprising connection bars 616 and the other connection portion 606 comprising vertical bars 608. FIG. 9A shows frame 600 as having three connection portions 606, while the same frame 600, shown in FIG. 9B, shows two connection portions 606 and a plurality of vertical bars 608. The frames shown in FIGS. 9A and 9B are identical, however, with one being shown in a closed configuration (FIG. 9A) and the other being shown in a closed configuration (FIG. 9B).

Connection portions 606 are shown in FIG. 9B, for example, as being elements of an exemplary frame 600 coupling to one or more of superior arm(s) 602, inferior arm(s) 604, vertical bar(s) 608, and lower arm(s) 614. In at least one embodiment, and as shown in FIG. 9B, connection portions 606 comprise a plurality of connection bars 616, which are used to connect one or more processed ligaments 50 and/or visceral pleura 60 to frame 600 as referenced herein with respect to other frame 600 and/or product 100 embodiments.

FIG. 10A shows an exemplary processed ligament 50 and/or visceral pleura 60 of the present disclosure molded for use with as a trileaflet valve 400. As shown in FIGS. 9A and 9B, frame 600 is configured as three leaves with two or three connection portions 606, depending on how the frame 600 is viewed. The processed ligament 50 and/or visceral pleura 60, as shown in FIG. 10A, is shaped substantially similar to an outer perimeter of frame 600 shown in FIGS. 9A and 9B. The shape shown in FIG. 7A represents processed ligament 50 and/or visceral pleura 60 configured so to create symmetrical valve leaflets upon placement of processed ligament 50 and/or visceral pleura 60 upon frame 600.

An exemplary embodiment of a product 100 of the present disclosure comprising a frame 600 as shown in FIGS. 9A and 9B and a processed ligament 50 and/or visceral pleura 60 attached thereto is shown in FIG. 10B. Product 100 is shown in a closed configuration in FIG. 10B, whereby processed ligament 50 and/or visceral pleura 60 is sutured to itself and/or to portions of frame 600 at multiple locations to hold the processed ligament 50 and/or visceral pleura 60 in place. As shown in FIG. 10B, product 100 is configured as a trileaflet valve 400, which may be used, for example, as a venous valve or another type of valve. Leaflets 802, 804, and 1000 are identified in FIG. 10B.

Various products 100 of the present disclosure configured as valves 400, including products 100 shown in FIGS. 8B and 10B for example, and/or other valve 400 products of the present disclosure used with or without various frames, can have the processed ligament 50 and/or visceral pleura 60 positioned in specific configuration(s) to improve overall operation, effectiveness, and/or size of said products 100. Visceral pleura 556, and therefore processed visceral pleura 60, has one side with mesothelium (also referred to herein as a relatively smooth “mesothelial side”), and has an opposite side without mesothelium (also referred to herein as a relatively rough “non-mesothelial side”). As shown in FIG. 5F, the mesothelial side 860 of visceral pleura 556 is on a relative outside of the lung 34, while the non-mesothelial side 862 of visceral pleura 556 is on the relative inside of the lung 34.

For example, and in connection with various products 100 of the present disclosure using processed visceral pleura 60 as one or more valve 400 leaflets 802, 804, or 1000, processed visceral pleura 60 can be positioned in a way/configuration so that the side of processed visceral pleura 60 having mesothelium would be on the relative back of the valve 400 leaflet(s) 802, 804, and/or 1000, and so that the side of processed visceral pleura 60 without mesothelium would be on the relative front of the valve 400 leaflet(s) 802, 804, and/or 1000. In such a configuration, the mesothelial side 860 of processed visceral pleura 60 is on the back of leaflet(s) 802, 804, and/or 1000, where blood flow reversal exists as the valve 400 closes. The relatively smooth mesothelial side 860 would be in contact with blood flows more slowly, where shear stresses may be lower and reversing. As such, the rougher non-mesothelial 862 side of processed visceral pleura 60 would then be on the front of leaflet(s) 802, 804, and/or 1000, in contact with fast moving blood, because there is less of a risk of thrombosis as compared with the slower moving blood or shear stress.

Such a valve 400 (exemplary product 100) embodiment is shown in FIG. 10C positioned within a luminal organ 850, where valve leaflets 802, 804 (or more, less, or different leaflets, depending on valve 400 configuration) are shown therein. As shown therein, valve 400 is in contact with the wall(s) 852 of luminal organ 850, positioned within a lumen 854 defined therethrough. A mesothelial side 860 of processed visceral pleura 60 is on a relative back of leaflets 802, 804, and a non-mesothelial side 862 of processed visceral pleura 60 is on a relative front of leaflets 802, 804, as described above. Such a device embodiment 100 is one such embodiment referenced herein where processed ligament 50 and/or visceral pleura 60 is oriented in a specific direction. In at least another embodiment, for example, mesothelial side 860 of processed visceral pleura 60 would be on a relative front of leaflets 802, 804, and a non-mesothelial side 862 of processed visceral pleura 60 would be on a relative back of leaflets 802, 804.

Exemplary products 100 of the present disclosure may be prepared as follows. In at least one method for preparing a product of the present disclosure, the method 1100, as shown by the method steps in FIG. 11, comprises the steps of preparing a bodily tissue (such as a processed ligament 50 and/or visceral pleura 60 or another bodily tissue having the necessary stretchability and durability properties necessary to be useful in connection with one or more products 100 of the present disclosure) (an exemplary tissue preparation step 1102, which may be optional, as the tissue may have been previously prepared and subsequently used in connection with method 1100), and shaping the bodily tissue (an exemplary tissue shaping step 1104) so that the tissue will fit around portions of an exemplary frame 600. In at least one embodiment, tissue preparation step comprises preparing a portion of tissue (such as pulmonary ligament 50 and/or visceral pleura 60) by way of excising the tissue from a mammalian body, removing any undesirable portions of tissue (such as those with holes or vessels therein), placing the tissue on a frame (to maintain a desired shape and/or amount of stretch), and fixing the tissue using glutaraldehyde and buffer, for example. Tissue shaping step 1104, in at least one embodiment, comprises stretching the tissue (such as lung ligament 50, visceral pleura 60, lung viscera, and/or another tissue) and cutting the tissue using a flat mold, for example.

In various embodiments, method 1100 further comprises the step of positioning the tissue around a mount (such as a cylindrical or conical mount, which may be made of acrylic or another suitable material) (an exemplary mounting step 1106), and positioning at least part of an exemplary frame 600 around the tissue positioned upon the mount (an exemplary frame positioning step 1108). Tissue may then be passed around various bars of frame 600 (such as connection bars 616 of connection portion 606 or other components of frame 600), such as shown in FIG. 7B (an exemplary tissue connection step 1110), and various sutures 800 may be used to suture portions of tissue together to form the overall relatively cylindrical shape (an exemplary suturing step 1112). Tissue connection step 1110 may be repeated, such as by allowing the inflow portion of the tissue cylinder to pass through the superior and inferior parallel arms (arms 602, 604) to cover arms 602, 604, as shown in FIG. 8A, for example. Additional sutures may then be used, by way of repeating suturing step 1112, so that the border of the tissue is sutured with, for example, a continuing suture line facilitated by using a polypropylene 7-0 or 8-0 needle, for example, or another type/size of needle, to result in a product 100 as shown in FIGS. 8B, 10B, or in other product 100 embodiments.

After product 100 is prepared, it can be delivered into a mammalian luminal organ in a number of ways. One method of delivery involves gently crimping or compressing product 100 so that its overall cross-section decreases, to facilitate delivery into the luminal organ. This delivery may be facilitated using a catheter or a wire, for example. If delivered by catheter, and it at least one embodiment (such as with a nickel-cadmium product 100 of the present disclosure), a balloon catheter may be used, with product 100 positioned at the balloon. Inflation of the balloon, using a gas or a liquid, for example, can cause the balloon to expand and thus cause product 100 to expand and be positioned within the luminal organ. Deflation of the balloon can then facilitate removal of the catheter. Furthermore, products 100 of the present disclosure may be autoexpandable, such as those comprising nitinol, whereby delivery using a balloon catheter may not be necessary. Delivery of products 100 of the present disclosure is not limited to the aforementioned delivery methods, as other methods of delivering implantable devices into a mammalian luminal organ may be used to deliver products 100.

The present disclosure also includes disclosure of uses of various processed ligaments 50, processed visceral pleura 60, and/or products 100 in connection with various Transcatheter Aortic-Valve Implantation (TAVI) and other percutaneous approaches. TAVI involves the placement of an aortic valve within a patient using a catheter to avoid a traditional open surgical procedure and to minimize general stresses to the patient during the procedure. This procedure is used when a patient's aortic valve fails to operate as desired, and can effectively prolong the patient's life without requiring additional surgical and non-surgical procedures, including but not limited to heart transplant. Certain patients may not be suitable for surgery, such as those with such a severe aortic stenosis that would preclude an open surgical procedure, allowing TAVI to be considered. Processed ligaments 50 and/or processed visceral pleura 60 of the present disclosure can be used with current or potentially developed aortic valve frames/housings, or products 100 of the present disclosure comprising one or more frames 600, can be used as aortic or other valves as referenced herein. Furthermore, various processed ligaments 50, processed visceral pleura 60, and/or products 100 can be delivered percutaneously or surgically, using various catheters or wires or other surgical tools for example, avoiding more invasive surgical procedures.

As processed lung ligaments 50 and processed visceral pleura 60 of the present disclosure are thinner than pericardium, which is currently used in TAVI or used with any number of valve procedures to replace and/or insert various aortic, mitral, pulmonary, tricuspid, and/or other percutaneous valves, the overall dimensions of the final delivery system, whether it be a product 100 of the present disclosure or processed ligament 50 and/or processed visceral pleura 60 of the present disclosure coupled with another type of frame or housing, can be significantly reduced by using processed ligaments 50 and/or processed visceral pleura 60 instead of pericardium. The bulk of a traditional TAVI product is not the stent frame itself, but the pericardial tissue, and using processed ligament 50 and/or processed visceral pleura 60 of the present disclosure instead of pericardial tissue would notably and beneficially decrease the overall bulk of said product 100. Having a product 100 configured smaller than a traditional TAVI product, for example, would not only allow for more potential manipulation of said product 100 in connection with delivery, expansion, and/or placement as compared to traditional products, but also would allow for smaller delivery devices (catheters, for example) to be used, therefore decreasing the potential aperture/opening made into a femoral or iliac artery, for example, during product 100 delivery. For example, reducing a catheter from 18 French to 12 French, or from 12 French to 8 French, would permit a smaller delivery aperture/opening to be used. This would also reduce or eliminate the need for a potential closure device, reduce patient bleeding, reduce overall patient trauma, and/or simplify delivery, placement, and/or expansion of relatively smaller products 100.

There are various advantages to using products 100 of the present disclosure as valves and/or as other medical implantable devices. For example, and with various embodiments described herein, products 100 are configured to avoid suture of commissure and thus spread out the stress, and there is may be no sutures 800 that come in contact with blood. Frames 600 may have a less metallic stent design, and may also comprise a completed inflow metal stent tissue cover. With respect to the different product 100 borders, various products 100 of the present disclosure have no suture line at the inflow border, and no tissue (such as processed lung ligament 50 and/or visceral pleura 60) fixation at the stent border. The double parallel (or relatively/substantially parallel) arms (superior arm(s) 602 and inferior arm(s) 604)) are configured so that a tissue (such as ligament 50 and/or visceral pleura 60) can be passed around them. Furthermore, and in at least one product 100 embodiment, the suture line is not submitted to the inflow stress and blood flow, and the suture knot is not in contact with the inflow blood.

Other advantages of products 100 of the present disclosure also exist. For example, and when preparing said products 100, the commissure are obtained by passing the tissue around the various vertical arms with the advantage of no suture and diffuse tissue stress along the vertical length of the bars. The various frame 600 designs and their tissue covers have the advantage of very little contact of any metallic frame material with the blood flow. The valves themselves have excellent leaflet coaptation, good valve sinus formation, and no blood stagnation areas when developed/configured as described herein and used within a mammalian blood vessel. Furthermore, the inflow stent area covered with tissue is in broad contact with the venous wall with the advantage of tissue-tissue contact when positioned within a mammalian vein.

While various embodiments of biological tissue products and methods of using and generating the same have been described in considerable detail herein, the embodiments are merely offered as non-limiting examples of the disclosure described herein. It will therefore be understood that various changes and modifications may be made, and equivalents may be substituted for elements thereof, without departing from the scope of the present disclosure. The present disclosure is not intended to be exhaustive or limiting with respect to the content thereof.

Further, in describing representative embodiments, the present disclosure may have presented a method and/or a process as a particular sequence of steps. However, to the extent that the method or process does not rely on the particular order of steps set forth therein, the method or process should not be limited to the particular sequence of steps described, as other sequences of steps may be possible. Therefore, the particular order of the steps disclosed herein should not be construed as limitations of the present disclosure. In addition, disclosure directed to a method and/or process should not be limited to the performance of their steps in the order written. Such sequences may be varied and still remain within the scope of the present disclosure.

Claims

1. A product, comprising: a frame configured to retain a mammalian tissue thereon; andthe mammalian tissue coupled to the frame;wherein when the product is positioned within a mammalian luminal organ, fluid native to the mammalian luminal organ may pass through a lumen defined within the product;wherein the mammalian tissue comprises mammalian pulmonary ligament; andwherein the mammalian tissue is fixed.
2. The product of claim 1, wherein the mammalian tissue is chemically fixed.
3. The product of claim 1, wherein the mammalian tissue is fixed using a fixative selected from the group consisting of glutaraldehyde, formaldehyde, and glycerol.
4. The product of claim 1, wherein the mammalian tissue is fixed using a fixative within a HEPES or phosphate buffer.
5. The product of claim 1, wherein the mammalian tissue is fixed using a fixation procedure selected from the group consisting of aqueous fixation, cryo-preservation, and dry tissue fixation.
6. The product of claim 1, wherein the mammalian tissue is fixed using a fixative that is buffered.
7. The product of claim 1, wherein a segment of the mammalian tissue is decellularized.
8. The product of claim 1, wherein the mammalian tissue is sterilized.
9. A product, comprising: a frame configured to retain a mammalian tissue thereon; andthe mammalian tissue coupled to the frame;wherein when the product is positioned within a mammalian luminal organ, fluid native to the mammalian luminal organ may pass through a lumen defined within the product;wherein the product is configured as a stent valve;wherein the mammalian tissue comprises pulmonary ligament; andwherein the mammalian tissue is fixed.
10. The product of claim 9, wherein the mammalian tissue is chemically fixed.
11. The product of claim 9, wherein the mammalian tissue is fixed using a fixative selected from the group consisting of glutaraldehyde, formaldehyde, and glycerol.
12. The product of claim 9, wherein a segment of the mammalian tissue is decellularized.

PRIORITY

The present application is related to, and claims the priority benefit of, U.S. Provisional Patent Application Ser. No. 61/640,381, filed Apr. 30, 2012, and U.S. Provisional Patent Application Ser. No. 61/597,406, filed Feb. 10, 2012, the contents of which are hereby incorporated by reference in their entirety into this disclosure.

PCT Information

Filing Document	Filing Date	Country	Kind
PCT/US2013/025591	2/11/2013	WO	00

Publishing Document	Publishing Date	Country	Kind
WO2013/120082	8/15/2013	WO	A

US Referenced Citations (1231)

Number	Name	Date	Kind
3012882	Muldawer et al.	Dec 1961	A
3014104	Cobine et al.	Dec 1961	A
3063967	Schultz	Nov 1962	A
3169945	Hostettler et al.	Feb 1965	A
3174851	Buehler et al.	Mar 1965	A
3391126	Baggett et al.	Jul 1968	A
3464065	Cromie	Sep 1969	A
3583391	Cox et al.	Jun 1971	A
3589392	Meyer	Jun 1971	A
3645941	Snapp et al.	Feb 1972	A
3710744	Goodenough et al.	Jan 1973	A
3736598	Bellhouse et al.	Jun 1973	A
3737919	Child	Jun 1973	A
3772137	Tolliver	Nov 1973	A
3912692	Casey et al.	Oct 1975	A
3942532	Hunter et al.	Mar 1976	A
3953566	Gore	Apr 1976	A
3983581	Angell et al.	Oct 1976	A
4052988	Doddi et al.	Oct 1977	A
4076807	Trinh et al.	Feb 1978	A
4093061	Horak	Jun 1978	A
4106129	Carpentier et al.	Aug 1978	A
4218782	Rygg	Aug 1980	A
4222126	Boretos et al.	Sep 1980	A
4243775	Rosensaft et al.	Jan 1981	A
4274292	Angell	Jan 1981	A
4272854	Bokros	Jun 1981	A
4275469	Gabbay	Jun 1981	A
4297749	Davis et al.	Nov 1981	A
4300565	Rosensaft et al.	Nov 1981	A
4328592	Klawitier	May 1982	A
4340977	Brownlee et al.	Jul 1982	A
4345340	Rosen	Aug 1982	A
4350492	Wright et al.	Sep 1982	A
4364126	Rosen	Dec 1982	A
4429080	Casey et al.	Jan 1984	A
4440789	Mattel et al.	Apr 1984	A
4441216	Ionescu et al.	Apr 1984	A
4470157	Love	Sep 1984	A
4494531	Gianturco	Jan 1985	A
4506394	Bedard	Mar 1985	A
4535483	Klawitter et al.	Aug 1985	A
4549921	Wolfe, Jr.	Oct 1985	A
4559945	Koelmel et al.	Dec 1985	A
4564014	Fogarty	Jan 1986	A
4580568	Gianturco	Apr 1986	A
4591630	Gertzman et al.	May 1986	A
4605730	Shalaby et al.	Aug 1986	A
4624256	Messier et al.	Nov 1986	A
4643732	Pietsch et al.	Feb 1987	A
4643734	Lin	Feb 1987	A
4653497	Bezwada et al.	Mar 1987	A
4657024	Coneys	Apr 1987	A
4661300	Daugherty	Apr 1987	A
4665906	Jervis	May 1987	A
4665918	Garza et al.	May 1987	A
4666442	Arru et al.	May 1987	A
4675361	Ward et al.	Jun 1987	A
4681588	Ketharanathan	Jul 1987	A
4692164	Dzemeshkevich	Sep 1987	A
4700704	Jamiolkowski et al.	Oct 1987	A
4731074	Rousseau et al.	Mar 1988	A
4731075	Gallo Mezo et al.	Mar 1988	A
4755593	Lauren	Jul 1988	A
4759758	Gabbay	Jul 1988	A
4762129	Bonzel	Aug 1988	A
4776337	Palmaz	Oct 1988	A
4787901	Baykut	Nov 1988	A
4788979	Jarrett et al.	Dec 1988	A
4791929	Jarrett et al.	Dec 1988	A
4798611	Freeman	Jan 1989	A
4800603	Jaffe	Jan 1989	A
4806595	Noishiki et al.	Feb 1989	A
4816028	Kapadia	Mar 1989	A
4816029	Penny et al.	Mar 1989	A
4832055	Palestrant	May 1989	A
4836204	Landymore et al.	Jun 1989	A
4838267	Jamiolkowski et al.	Jun 1989	A
4851000	Gupta	Jul 1989	A
4856510	Kowalewski	Aug 1989	A
4856516	Hillstead	Aug 1989	A
4861830	Ward et al.	Aug 1989	A
4872875	Hwang	Oct 1989	A
4893623	Rosenbluth	Jan 1990	A
4902508	Badylak et al.	Feb 1990	A
4911163	Fina	Mar 1990	A
4917089	Sideris	Apr 1990	A
4923465	Knock et al.	May 1990	A
4952215	Ouriel et al.	Aug 1990	A
4956178	Badylak et al.	Sep 1990	A
4969458	Wiktor	Nov 1990	A
4992027	Acosta	Feb 1991	A
4994071	MacGregor	Feb 1991	A
4994074	Bezwada et al.	Feb 1991	A
4994077	Dobben	Feb 1991	A
5007923	Bezwada et al.	Apr 1991	A
5017664	Grasel et al.	May 1991	A
5019085	Hillstead	May 1991	A
5020612	Williams	Jun 1991	A
5024671	Tu et al.	Jun 1991	A
5024841	Chu et al.	Jun 1991	A
5035706	Gianturco et al.	Jul 1991	A
5037434	Lane	Aug 1991	A
5041126	Gianturco	Aug 1991	A
5047048	Bezwada et al.	Sep 1991	A
5053008	Bajaj	Oct 1991	A
5067491	Taylor, II et al.	Nov 1991	A
5076807	Bezwada et al.	Dec 1991	A
5080665	Jarrett et al.	Jan 1992	A
5080670	Imamura et al.	Jan 1992	A
5085629	Goldberg et al.	Feb 1992	A
5100433	Bezwada et al.	Mar 1992	A
5103817	Reisdorf et al.	Apr 1992	A
5104402	Melbin	Apr 1992	A
5104404	Wolff	Apr 1992	A
5108420	Marks	Apr 1992	A
5108425	Hwang	Apr 1992	A
5110064	Kimura et al.	May 1992	A
5116365	Hillstead	May 1992	A
5116564	Jansen et al.	May 1992	A
5133725	Quadri	Jul 1992	A
5133755	Brekke	Jul 1992	A
5139515	Robicsek	Aug 1992	A
5163953	Vince	Nov 1992	A
5167628	Boyles	Dec 1992	A
5171259	Inoue	Dec 1992	A
5174295	Christian et al.	Dec 1992	A
5176692	Wilk et al.	Jan 1993	A
5178618	Kandarpa	Jan 1993	A
5178632	Hanson	Jan 1993	A
5178633	Peters	Jan 1993	A
5192301	Kamiya et al.	Mar 1993	A
5192313	Budd et al.	Mar 1993	A
5197979	Quintero et al.	Mar 1993	A
5197980	Gorshkov	Mar 1993	A
5201314	Bosley et al.	Apr 1993	A
5201757	Heyn et al.	Apr 1993	A
5226889	Sheiban	Jul 1993	A
5234457	Andersen	Aug 1993	A
5239982	Trauthen	Aug 1993	A
5258000	Gianturco	Nov 1993	A
5275826	Badylak et al.	Jan 1994	A
5281422	Badylak et al.	Jan 1994	A
5282824	Gianturco	Feb 1994	A
5284488	Sideris	Feb 1994	A
5289831	Bosley	Mar 1994	A
5293879	Vonk et al.	Mar 1994	A
5306294	Winston et al.	Apr 1994	A
5314444	Gianturco	May 1994	A
5314472	Fontaine	May 1994	A
5314473	Godin	May 1994	A
5322062	Servas	Jun 1994	A
5327891	Rammler	Jul 1994	A
5334210	Gianturco	Aug 1994	A
5334217	Das	Aug 1994	A
5342387	Summers	Aug 1994	A
5344426	Lau et al.	Sep 1994	A
5352240	Ross	Oct 1994	A
5358518	Camilli	Oct 1994	A
5366473	Winston et al.	Nov 1994	A
5366479	McGarry et al.	Nov 1994	A
5370685	Stevens	Dec 1994	A
5376113	Jansen et al.	Dec 1994	A
5380320	Morris	Jan 1995	A
5383892	Cardon et al.	Jan 1995	A
5387235	Chuter	Feb 1995	A
5389106	Tower	Feb 1995	A
5393594	Koyfman et al.	Feb 1995	A
5397311	Walker	Mar 1995	A
5397331	Himpens et al.	Mar 1995	A
5397355	Marin et al.	Mar 1995	A
5405377	Cragg	Apr 1995	A
5405381	Olin	Apr 1995	A
5411552	Andersen	May 1995	A
5412068	Tang et al.	May 1995	A
5413599	Imachi et al.	May 1995	A
5417708	Hall et al.	May 1995	A
5421955	Lau et al.	Jun 1995	A
5425744	Fagan et al.	Jun 1995	A
5433727	Sideris	Jul 1995	A
5441515	Khosravi et al.	Aug 1995	A
5443496	Schwartz	Aug 1995	A
5449373	Pinchasik	Sep 1995	A
5451235	Lock et al.	Sep 1995	A
5456713	Chuter	Oct 1995	A
5468253	Bezwada et al.	Nov 1995	A
5486193	Bourne	Jan 1996	A
5486195	Myers et al.	Jan 1996	A
5489297	Duran	Feb 1996	A
5500014	Quijano	Mar 1996	A
5507767	Maeda et al.	Apr 1996	A
5507771	gianturco	Apr 1996	A
5514154	Lau et al.	May 1996	A
5522841	Roby et al.	Jun 1996	A
5527354	Fontaine et al.	Jun 1996	A
5530683	Lindberg	Jun 1996	A
5540712	Kleshinski et al.	Jul 1996	A
5540713	Schnepp-Pesch et al.	Jul 1996	A
5545215	Duran	Aug 1996	A
5549662	Fordenbacher	Aug 1996	A
5549663	Cottone, Jr.	Aug 1996	A
5549665	Vesely et al.	Aug 1996	A
5554119	Harrison et al.	Sep 1996	A
5554181	Das	Sep 1996	A
5554185	Block et al.	Sep 1996	A
5554389	Badylak et al.	Sep 1996	A
5562728	Lazarus et al.	Oct 1996	A
5562729	Purdy	Oct 1996	A
5571168	Toro	Nov 1996	A
5589563	Ward et al.	Dec 1996	A
5591197	Orth et al.	Jan 1997	A
5591198	Boyle et al.	Jan 1997	A
5595571	Jaffe	Jan 1997	A
5603698	Roberts et al.	Feb 1997	A
5607442	Fischell et al.	Mar 1997	A
5607445	Summers	Mar 1997	A
5607465	Camilli	Mar 1997	A
5609598	Laufer et al.	Mar 1997	A
5613981	Boyle et al.	Mar 1997	A
5624449	Pham et al.	Apr 1997	A
5628791	Bokros et al.	May 1997	A
5630829	Lauterjung	May 1997	A
5632771	Boatman et al.	May 1997	A
5634936	Linden et al.	Jun 1997	A
5636641	Fariabi	Jun 1997	A
5641324	Bokros et al.	Jun 1997	A
5643312	Fischell et al.	Jul 1997	A
5643317	Pavcnik et al.	Jul 1997	A
5653727	Wiktor	Aug 1997	A
5662675	Polansky et al.	Sep 1997	A
5667523	Bynon et al.	Sep 1997	A
5668288	Storey et al.	Sep 1997	A
5669933	Simon et al.	Sep 1997	A
5681346	Orth et al.	Oct 1997	A
5683411	Kavteladze et al.	Nov 1997	A
5690642	Osborne et al.	Nov 1997	A
5697971	Fischell et al.	Dec 1997	A
5702372	Nelson	Dec 1997	A
5702421	Schneidt	Dec 1997	A
5705181	Cooper et al.	Jan 1998	A
5707389	Louw et al.	Jan 1998	A
5709707	Lock et al.	Jan 1998	A
5711969	Patel et al.	Jan 1998	A
5713920	Bezwada et al.	Feb 1998	A
5713950	Cox	Feb 1998	A
5713953	Vallana et al.	Feb 1998	A
5720777	Jaffe	Feb 1998	A
5725519	Penner	Mar 1998	A
5725534	Rasmussen	Mar 1998	A
5725572	Lam et al.	Mar 1998	A
5728158	Lau et al.	Mar 1998	A
5733303	Israel et al.	Mar 1998	A
5733325	Robinson et al.	Mar 1998	A
5733337	Carr, Jr. et al.	Mar 1998	A
5735893	Lau et al.	Apr 1998	A
5741327	Frantzen	Apr 1998	A
5749919	Blanc	May 1998	A
5755776	Al-Saadon	May 1998	A
5755777	Chuter	May 1998	A
5755778	Kleshinski	May 1998	A
5755781	Jayaraman	May 1998	A
5755782	Love	May 1998	A
5759192	Saunders	Jun 1998	A
5762625	Igaki	Jun 1998	A
5766238	Lau et al.	Jun 1998	A
5769780	Hata et al.	Jun 1998	A
5769796	Palermo et al.	Jun 1998	A
5772632	Forman	Jun 1998	A
5776161	Globerman	Jul 1998	A
5776188	Shepherd et al.	Jul 1998	A
5779670	Melman et al.	Jul 1998	A
5779729	Severini	Jul 1998	A
5792114	Fiore	Aug 1998	A
5792144	Fischell et al.	Aug 1998	A
5797952	Klein	Aug 1998	A
5797960	Stevens et al.	Aug 1998	A
5797953	Tekulve	Sep 1998	A
5800456	Maeda et al.	Sep 1998	A
5800526	Andersen et al.	Sep 1998	A
5807404	Richter	Sep 1998	A
5810847	Laufer et al.	Sep 1998	A
5814061	Osborne et al.	Sep 1998	A
5824041	Freislinger et al.	Oct 1998	A
5824042	Lombardi et al.	Oct 1998	A
5824045	Alt	Oct 1998	A
5824049	Ragheb et al.	Oct 1998	A
5824062	Patke et al.	Oct 1998	A
5824063	Cox	Oct 1998	A
5827237	Macoviak et al.	Oct 1998	A
5833694	Poncet	Oct 1998	A
5830209	Savage et al.	Nov 1998	A
5833671	Macoviak et al.	Nov 1998	A
5836964	Richter et al.	Nov 1998	A
5840081	Andersen et al.	Nov 1998	A
5843090	Schuetz	Dec 1998	A
5843117	Alt et al.	Dec 1998	A
5843180	Jaffe et al.	Dec 1998	A
5843181	Jaffe et al.	Dec 1998	A
5846247	Unworth et al.	Dec 1998	A
5846261	Kotula et al.	Dec 1998	A
5851232	Lois	Dec 1998	A
5853422	Huebsch et al.	Dec 1998	A
5855597	Jayaraman	Jan 1999	A
5855600	Alt	Jan 1999	A
5855601	Bessler et al.	Jan 1999	A
5855602	Angell	Jan 1999	A
5861003	Latson et al.	Jan 1999	A
5865723	Love	Feb 1999	A
5876445	Andersen et al.	Mar 1999	A
5876448	Thompson et al.	Mar 1999	A
5879305	Yock et al.	Mar 1999	A
5879366	Shaw et al.	Mar 1999	A
5879382	Boneau	Mar 1999	A
5885619	Patel et al.	Mar 1999	A
5891128	Gia et al.	Apr 1999	A
5891193	Robinson et al.	Apr 1999	A
5891195	Klostermeyer et al.	Apr 1999	A
5895419	Tweden et al.	Apr 1999	A
5895420	Mirsch, II et al.	Apr 1999	A
5902334	Dwyer et al.	May 1999	A
5907893	Zadno-Azizi et al.	Jun 1999	A
5908452	Bokros et al.	Jun 1999	A
5911732	Hojeibane	Jun 1999	A
5925063	Khosravi	Jul 1999	A
5926016	Pattantyus	Jul 1999	A
5928248	Acker	Jul 1999	A
5928258	Kahn	Jul 1999	A
5935148	Villar et al.	Aug 1999	A
5935161	Robinson	Aug 1999	A
5937861	Augustine	Aug 1999	A
5938682	Hojeibane	Aug 1999	A
5944733	Engelson	Aug 1999	A
5944738	Amplatz et al.	Aug 1999	A
5947995	Samuels	Sep 1999	A
5947997	Pavcnik et al.	Sep 1999	A
5954766	Zadno-Azizi et al.	Sep 1999	A
5955110	Patel et al.	Sep 1999	A
5957949	Leonhardt et al.	Sep 1999	A
5960642	Kim et al.	Oct 1999	A
5961546	Robinson et al.	Oct 1999	A
5968096	Whitson et al.	Oct 1999	A
5980565	Jayaraman	Nov 1999	A
5980799	Martakos et al.	Nov 1999	A
5981195	Fuller et al.	Nov 1999	A
5993844	Abraham et al.	Nov 1999	A
5997573	Quijano et al.	Dec 1999	A
6004347	McNamara et al.	Dec 1999	A
6007521	Melman	Dec 1999	A
6010531	Donlon et al.	Jan 2000	A
6015431	Thornton et al.	Jan 2000	A
6017363	Hojeibane	Jan 2000	A
6022359	Frantzen et al.	Feb 2000	A
6022374	Imran	Feb 2000	A
6024690	Lee et al.	Feb 2000	A
6027525	Suh et al.	Feb 2000	A
6033398	Farley et al.	Mar 2000	A
6036687	Laufer et al.	Mar 2000	A
6042606	Frantzen	Mar 2000	A
6053940	Wijay	Apr 2000	A
6056775	Borghi et al.	May 2000	A
6059757	Macoviak et al.	May 2000	A
6059779	Mills	May 2000	A
6059826	Bokros	May 2000	A
6059827	Fenton	May 2000	A
6063113	Kavteladze et al.	May 2000	A
6074419	Healy et al.	Jun 2000	A
6077281	Das	Jun 2000	A
6077291	Das	Jun 2000	A
6077295	Limon et al.	Jun 2000	A
6077296	Shokoohi et al.	Jun 2000	A
6080182	Shaw et al.	Jun 2000	A
6090035	Campbell	Jul 2000	A
6090127	Globerman	Jul 2000	A
6096027	Layne	Aug 2000	A
6096052	Callister et al.	Aug 2000	A
6099561	Alt	Aug 2000	A
6099567	Badylak et al.	Aug 2000	A
6110191	Dehdashtian	Aug 2000	A
6110201	Quijano et al.	Aug 2000	A
6110212	Gregory	Aug 2000	A
6096070	Ragneb et al.	Sep 2000	A
6113623	Sgro	Sep 2000	A
6117157	Tekulve	Sep 2000	A
6117159	Huebsch et al.	Sep 2000	A
6117979	Hendriks et al.	Sep 2000	A
6123721	Jang	Sep 2000	A
6126685	Lenker	Oct 2000	A
6126686	Badylak et al.	Oct 2000	A
6129755	Mathis et al.	Oct 2000	A
6132460	Thompson	Oct 2000	A
6132461	Thompson	Oct 2000	A
6136025	Barbut et al.	Oct 2000	A
6139575	Shu et al.	Oct 2000	A
6143016	Bleam	Nov 2000	A
6143022	Shull et al.	Nov 2000	A
6146416	Andersen et al.	Nov 2000	A
6149660	Laufer et al.	Nov 2000	A
6149680	Shelso	Nov 2000	A
6159237	Alt et al.	Dec 2000	A
6162245	Jayaraman	Dec 2000	A
6168614	Andersen et al.	Jan 2001	B1
6168617	Blaeser et al.	Jan 2001	B1
6174331	Moe et al.	Jan 2001	B1
6176875	Lenker	Jan 2001	B1
6178968	Louw et al.	Jan 2001	B1
6179858	Squire et al.	Jan 2001	B1
6183511	Patke et al.	Feb 2001	B1
6183512	Howanec et al.	Feb 2001	B1
6187036	Shaolian et al.	Feb 2001	B1
6187039	Hiles et al.	Feb 2001	B1
6190406	Durerig et al.	Feb 2001	B1
6193731	Oppelt	Feb 2001	B1
6197049	Shaolian et al.	Mar 2001	B1
6200336	Pavcnik et al.	Mar 2001	B1
6206907	Marino et al.	Mar 2001	B1
6206931	Cook et al.	Mar 2001	B1
6214029	Thill et al.	Apr 2001	B1
6216493	Weston et al.	Apr 2001	B1
6221091	Khosravi	Apr 2001	B1
6231507	Zikorus et al.	May 2001	B1
6231561	Frazier et al.	May 2001	B1
6231598	Berry	May 2001	B1
6235050	Quiachon et al.	May 2001	B1
6235053	Jang	May 2001	B1
6238409	Hojeibane	May 2001	B1
6238416	Sideris	May 2001	B1
6241763	Drasler et al.	Jun 2001	B1
6245102	Jayaraman	Jun 2001	B1
6254611	Vrba	Jul 2001	B1
6254631	Thompson	Jul 2001	B1
6254636	Peredo	Jul 2001	B1
6254642	Taylor	Jul 2001	B1
6264700	Kilcoyne et al.	Jul 2001	B1
6280467	Leonhardt	Aug 2001	B1
6233968	Taheri	Sep 2001	B1
6283990	Kanesaka	Sep 2001	B1
6287330	Johansson et al.	Sep 2001	B1
6287332	Bolz et al.	Sep 2001	B1
6287334	Moll et al.	Sep 2001	B1
6287336	Globerman et al.	Sep 2001	B1
6293966	Frantzen	Sep 2001	B1
6296657	Brucker	Oct 2001	B1
6299604	Ragheb et al.	Oct 2001	B1
6299635	Frantzen	Oct 2001	B1
6299636	Schmitt et al.	Oct 2001	B1
6299637	Shaplian	Oct 2001	B1
6312465	Griffin et al.	Nov 2001	B1
6312474	Francis et al.	Nov 2001	B1
6312549	Huang et al.	Nov 2001	B1
6315793	Bokros et al.	Nov 2001	B1
6319281	Patel	Nov 2001	B1
6325819	Pavcnik et al.	Dec 2001	B1
6328727	Frazier et al.	Dec 2001	B1
6328763	Love et al.	Dec 2001	B1
6334052	Nordstrand	Dec 2001	B1
6334871	Dor et al.	Jan 2002	B1
6334872	Termin et al.	Jan 2002	B1
6336938	Kavteladze et al.	Jan 2002	B1
6338730	Bonutti et al.	Jan 2002	B1
6338740	Carpentier	Jan 2002	B1
6340366	Wijay	Jan 2002	B2
6342067	Mathis et al.	Jan 2002	B1
6342070	Nguyen-Thien-Nhon	Jan 2002	B1
6346074	Roth	Feb 2002	B1
6348065	Brown et al.	Feb 2002	B1
6352554	De Paulis	Mar 2002	B2
6355052	Neuss et al.	Mar 2002	B1
6355056	Pinheiro	Mar 2002	B1
6355070	Andersen et al.	Mar 2002	B1
6358228	Tubman et al.	Mar 2002	B1
6358277	Duran	Mar 2002	B1
6358284	Fearnot et al.	Mar 2002	B1
6368338	Konya et al.	Apr 2002	B1
6371961	Osborne et al.	Apr 2002	B1
6371983	Lane	Apr 2002	B1
6375679	Martyn et al.	Apr 2002	B1
6375989	Badylak et al.	Apr 2002	B1
6379365	Diaz	Apr 2002	B1
6379710	Badylak	Apr 2002	B1
6383216	Kavteladze et al.	May 2002	B1
6383832	Stone	May 2002	B1
6395018	Castaneda	May 2002	B1
6409752	Boatman et al.	Jun 2002	B1
6415631	Weston et al.	Jul 2002	B1
6416542	Marcade et al.	Jul 2002	B1
6425914	Wallace et al.	Jul 2002	B1
6425916	Garrison	Jul 2002	B1
6428570	Globerman	Aug 2002	B1
6440163	Swanson et al.	Aug 2002	B1
6440164	DiMatteo et al.	Aug 2002	B1
6444229	Voytik-Harbin et al.	Sep 2002	B2
6451052	Burmeister et al.	Sep 2002	B1
6458137	Klint	Oct 2002	B1
6458153	Bailey et al.	Oct 2002	B1
6461382	Cao	Oct 2002	B1
6464720	Boatman	Oct 2002	B2
6471718	Staehle	Oct 2002	B1
6478819	Moe	Nov 2002	B2
6482228	Norred	Nov 2002	B1
6485500	Kokish et al.	Nov 2002	B1
6485510	Camrud et al.	Nov 2002	B1
6488702	Besselink	Dec 2002	B1
6494909	Greenhalgh	Dec 2002	B2
6503272	Duerig et al.	Jan 2003	B2
6508824	Flaherty et al.	Jan 2003	B1
6508833	Pavcnik	Jan 2003	B2
6508966	Castro et al.	Jan 2003	B1
6514063	Acciai et al.	Feb 2003	B2
6524336	Papazoglou et al.	Feb 2003	B1
6527800	McGuckin, Jr. et al.	Mar 2003	B1
6530951	Bates et al.	Mar 2003	B1
6533807	Wolinsky et al.	Mar 2003	B2
6544291	Taylor	Apr 2003	B2
6547815	Myers et al.	Apr 2003	B2
6553801	Chen	Apr 2003	B2
6558415	Thompson	May 2003	B2
6558418	Carpentier et al.	May 2003	B2
6558429	Taylor	May 2003	B2
6562065	Shanley	May 2003	B1
6565597	Fearnot et al.	May 2003	B1
6565600	Hojeibane	May 2003	B2
6572650	Abraham et al.	Jun 2003	B1
6579221	Peterson	Jun 2003	B1
6579307	Sarac	Jun 2003	B2
6579311	Makower	Jun 2003	B1
6579538	Spievack	Jun 2003	B1
6580568	Ozaki	Jun 2003	B2
6582462	Andersen et al.	Jun 2003	B1
6585761	Taheri	Jul 2003	B2
6589230	Gia et al.	Jul 2003	B2
6594880	Elsberry	Jul 2003	B2
6596021	Lootz	Jul 2003	B1
6598307	Love et al.	Jul 2003	B2
6599275	Fischer, Jr.	Jul 2003	B1
6602241	Makower et al.	Aug 2003	B2
6602286	Strecker	Aug 2003	B1
6605049	Wagner et al.	Aug 2003	B1
6613002	Clark et al.	Sep 2003	B1
6613086	Moe et al.	Sep 2003	B1
6616680	Thielen	Sep 2003	B1
6623506	McGuckin, Jr. et al.	Sep 2003	B2
6623508	Shaw et al.	Sep 2003	B2
6632196	Houser	Oct 2003	B1
6638300	Frantzen	Oct 2003	B1
6640412	Iancea	Nov 2003	B2
6656206	Corcoran et al.	Dec 2003	B2
6656216	Hossainy et al.	Dec 2003	B1
6663661	Boneau	Dec 2003	B2
6666885	Moe	Dec 2003	B2
6666886	Tranquillo et al.	Dec 2003	B1
6669724	Park et al.	Dec 2003	B2
6673100	Diaz et al.	Jan 2004	B2
6676694	Weiss	Jan 2004	B1
6676698	McGuckin, Jr. et al.	Jan 2004	B2
6678962	Love et al.	Jan 2004	B1
6685739	DiMatteo et al.	Feb 2004	B2
6689123	Pinchasik	Feb 2004	B2
6692458	Forman et al.	Feb 2004	B2
6706026	Goldstein et al.	Mar 2004	B1
6716241	Wilder et al.	Apr 2004	B2
6720402	Langer et al.	Apr 2004	B2
6726715	Sutherland	Apr 2004	B2
6730064	Ragheb et al.	May 2004	B2
6730117	Tseng et al.	May 2004	B1
6730118	Spenser et al.	May 2004	B2
6733525	Yang et al.	May 2004	B2
6746489	Dua et al.	Jun 2004	B2
6749622	McGuckin, Jr. et al.	Jun 2004	B2
6752826	Holloway et al.	Jun 2004	B2
6752828	Thornton	Jun 2004	B2
6761735	Eberhardt et al.	Jul 2004	B2
6767362	Schreck	Jul 2004	B2
6783499	Schwartz	Aug 2004	B2
6786922	Schaeffer	Sep 2004	B2
6790214	Kraemer et al.	Sep 2004	B2
6790218	Jayaraman	Sep 2004	B2
6790237	Stinson	Sep 2004	B2
6821292	Pazienza et al.	Nov 2004	B2
6823576	Austin	Nov 2004	B2
6830584	Seguin	Dec 2004	B1
6843802	Villalobos et al.	Jan 2005	B1
6859986	Jackson	Mar 2005	B2
6878162	Bales et al.	Apr 2005	B2
6896690	Lambrecht	May 2005	B1
6908481	Cribier	Jun 2005	B2
6911037	Gainor et al.	Jun 2005	B2
6915560	Austin	Jul 2005	B2
6918929	Udipi et al.	Jul 2005	B2
6921378	O'Keefe et al.	Jul 2005	B2
6932829	Majercak	Aug 2005	B2
6939377	Jayaraman et al.	Sep 2005	B2
6945978	Hyde	Sep 2005	B1
6945989	Betelia et al.	Sep 2005	B1
6949113	Van Tassel et al.	Sep 2005	B2
6949116	Solymar et al.	Sep 2005	B2
6953332	Kurk et al.	Oct 2005	B1
6958076	Acosta	Oct 2005	B2
6960220	Marino et al.	Nov 2005	B2
6962603	Brown et al.	Nov 2005	B1
6974474	Pavcnik et al.	Dec 2005	B2
6976995	Mathis et al.	Dec 2005	B2
6994092	Van der Burg et al.	Feb 2006	B2
6994717	Konya et al.	Feb 2006	B2
7011671	Welch	Mar 2006	B2
7018403	Pienknagura	Mar 2006	B1
7018404	Holmberg et al.	Mar 2006	B2
7018406	Seguin	Mar 2006	B2
7018407	Wright et al.	Mar 2006	B1
7025777	Moore	Apr 2006	B2
7025780	Gabbay	Apr 2006	B2
7025923	Harhen et al.	Apr 2006	B2
7029493	Majercak et al.	Apr 2006	B2
7044966	Svanidze et al.	May 2006	B2
7060088	Fischell et al.	Jun 2006	B1
7070616	Majercak et al.	Jul 2006	B2
7081131	Thornton	Jul 2006	B2
7087089	Patel	Aug 2006	B2
7101381	Ford et al.	Sep 2006	B2
7101395	Tremulis et al.	Sep 2006	B2
7101396	Svanidze et al.	Sep 2006	B2
7118600	Dua et al.	Oct 2006	B2
7125418	Duran et al.	Oct 2006	B2
7128073	van der Burg et al.	Oct 2006	B1
7128756	Lowe et al.	Oct 2006	B2
7128757	Osborne et al.	Oct 2006	B2
7128759	Osborne et al.	Oct 2006	B2
7144410	Marino et al.	Dec 2006	B2
7147661	Chobotov et al.	Dec 2006	B2
7153324	Case et al.	Dec 2006	B2
7160320	Duran	Jan 2007	B2
7163556	Xie et al.	Jan 2007	B2
7172625	Shu et al.	Feb 2007	B2
7179270	Makower	Feb 2007	B2
7182779	Acosta et al.	Feb 2007	B2
7186789	Hossainy et al.	Mar 2007	B2
7195641	Palmaz et al.	Mar 2007	B2
7232462	Schaeffer	Jun 2007	B2
7247167	Gabbay	Jul 2007	B2
7258697	Cox et al.	Aug 2007	B1
7261732	Justino	Aug 2007	B2
7273492	Cheng et al.	Sep 2007	B2
7288105	Oman et al.	Oct 2007	B2
7303571	Makower et al.	Dec 2007	B2
7323010	Verona et al.	Jan 2008	B2
7338520	Bailey et al.	Mar 2008	B2
7347869	Hojeibane et al.	Mar 2008	B2
7351256	Hojeibane et al.	Apr 2008	B2
7354455	Stinson	Apr 2008	B2
7361189	Case et al.	Apr 2008	B2
7364587	Dong et al.	Apr 2008	B2
7377938	Sarac et al.	May 2008	B2
7381219	Salahieh et al.	Jun 2008	B2
7399315	Iobbi	Jul 2008	B2
7402171	Osborne	Jul 2008	B2
7435257	Lashinski et al.	Oct 2008	B2
7445630	Lashinski et al.	Nov 2008	B2
7445631	Salahieh et al.	Nov 2008	B2
7452371	Pavcnik et al.	Nov 2008	B2
7491942	Black et al.	Feb 2009	B2
7503928	Case et al.	Mar 2009	B2
7520894	Pavcnik et al.	Apr 2009	B2
7524331	Birdsall	Apr 2009	B2
7524332	Osborne et al.	Apr 2009	B2
7534259	Lashinski et al.	May 2009	B2
7544205	Flagle et al.	Jun 2009	B2
7544207	Osborne et al.	Jun 2009	B2
7547322	Sarac et al.	Jun 2009	B2
7556645	Lashinski et al.	Jul 2009	B2
7563276	Osborne et al.	Jul 2009	B2
7563277	Case et al.	Jul 2009	B2
7566336	Corcoran et al.	Jul 2009	B2
7569071	Haverkost et al.	Aug 2009	B2
7582110	Case et al.	Sep 2009	B2
7585321	Cribier	Sep 2009	B2
7594927	Majercak et al.	Sep 2009	B2
7604661	Pavcnik et al.	Oct 2009	B2
7618447	Case et al.	Nov 2009	B2
7625395	Case et al.	Dec 2009	B2
7625399	Case et al.	Dec 2009	B2
7628803	Pavcnik et al.	Dec 2009	B2
7628804	Flagle et al.	Dec 2009	B2
7637937	Case et al.	Dec 2009	B2
7641686	Lashinski et al.	Jan 2010	B2
7648527	Agnew	Jan 2010	B2
7653455	Cinader, Jr.	Jan 2010	B2
7655288	Bauman et al.	Feb 2010	B2
7655584	Biran et al.	Feb 2010	B2
7658759	Case et al.	Feb 2010	B2
7658762	Lashinski et al.	Feb 2010	B2
7659219	Biran et al.	Feb 2010	B2
7670366	Case et al.	Mar 2010	B2
7678144	Bailey et al.	Mar 2010	B2
7686844	Case et al.	Mar 2010	B2
7736385	Agnew	Jun 2010	B2
7739971	Chambers et al.	Jun 2010	B2
7745532	Ruberti et al.	Jun 2010	B2
7806921	Hoffman	Oct 2010	B2
7815923	Johnson et al.	Oct 2010	B2
7819836	Levine et al.	Oct 2010	B2
7846199	Paul, Jr. et al.	Dec 2010	B2
7846203	Cribier	Dec 2010	B2
7850510	Farnsworth et al.	Dec 2010	B2
7854759	Shirley	Dec 2010	B2
7861570	Thomas	Jan 2011	B2
7871430	Pavcnik et al.	Jan 2011	B2
7918882	Pavcnik et al.	Apr 2011	B2
7935144	Lashinski et al.	May 2011	B2
7942887	Kraemer et al.	May 2011	B2
7955375	Agnew	Jun 2011	B2
7955376	Osborne et al.	Jun 2011	B2
7955377	Melsheimer	Jun 2011	B2
7964206	Suokas et al.	Jun 2011	B2
7979150	Lin et al.	Jul 2011	B2
7993410	Shin et al.	Aug 2011	B2
8012201	Lashinski et al.	Sep 2011	B2
8038708	Case et al.	Oct 2011	B2
8038710	Fearnot et al.	Oct 2011	B2
8048500	Drumheller et al.	Nov 2011	B2
8048503	Farnsworth et al.	Nov 2011	B2
8057532	Hoffman	Nov 2011	B2
8057540	Letac et al.	Nov 2011	B2
8092522	Paul, Jr. et al.	Jan 2012	B2
8100962	Agnew et al.	Jan 2012	B2
8109990	Paul et al.	Feb 2012	B2
8118877	Brauker et al.	Feb 2012	B2
8128686	Paul, Jr. et al.	Mar 2012	B2
8129477	Zhang et al.	Mar 2012	B1
8133213	Lashinski et al.	Mar 2012	B2
8133500	Ringeisen et al.	Mar 2012	B2
8157810	Case et al.	Apr 2012	B2
8157857	Case et al.	Apr 2012	B2
8197534	Osborne et al.	Jun 2012	B2
8211165	McIntosh et al.	Jul 2012	B1
8221492	Case et al.	Jul 2012	B2
8252043	Case et al.	Aug 2012	B2
8257429	Pavcnik	Sep 2012	B2
8273117	Palumbo et al.	Sep 2012	B2
8276533	Chambers et al.	Oct 2012	B2
8292938	Case	Oct 2012	B2
8303648	Grewe et al.	Nov 2012	B2
8303649	Agnew et al.	Nov 2012	B2
8308796	Lashinski et al.	Nov 2012	B2
8313526	Hoffman et al.	Nov 2012	B2
8317853	Agnew	Nov 2012	B2
8323332	Agnew	Dec 2012	B2
8337545	Osborne	Dec 2012	B2
8351126	Peng	Jan 2013	B2
8366741	Chin et al.	Feb 2013	B2
8366743	Zeng	Feb 2013	B2
8377118	Lashinski et al.	Feb 2013	B2
8403977	Case et al.	Mar 2013	B2
8403979	Paul, Jr.	Mar 2013	B2
8470020	Schaeffer et al.	Jun 2013	B2
8475512	Hunt	Jul 2013	B2
8475516	Paul et al.	Jul 2013	B2
8506621	Agnew et al.	Aug 2013	B2
8556881	Lashinski et al.	Oct 2013	B2
8568477	Lashinski et al.	Oct 2013	B2
8617205	Pavcnik et al.	Dec 2013	B2
8652197	Paul et al.	Feb 2014	B2
8663320	Chambers et al.	Mar 2014	B2
8679175	Paul, Jr. et al.	Mar 2014	B2
8702746	Tekulve et al.	Apr 2014	B2
8771338	Schaeffer et al.	Jul 2014	B2
20010001128	Holman et al.	May 2001	A1
20010004707	Dereume et al.	Jun 2001	A1
20010007956	Letac et al.	Jul 2001	A1
20010011187	Pavcnik et al.	Aug 2001	A1
20010016770	Allen et al.	Aug 2001	A1
20010018610	Limon	Aug 2001	A1
20010020189	Taylor	Sep 2001	A1
20010020190	Taylor	Sep 2001	A1
20010021872	Bailey et al.	Sep 2001	A1
20010025197	Shu et al.	Sep 2001	A1
20010034537	Shaw et al.	Oct 2001	A1
20010037129	Thill	Nov 2001	A1
20010039450	Pavcnik et al.	Nov 2001	A1
20010041930	Globerman et al.	Nov 2001	A1
20010044648	Wolinsky et al.	Nov 2001	A1
20010049553	De Paulis et al.	Dec 2001	A1
20020002400	Drasler et al.	Jan 2002	A1
20020019665	Dehdashtian et al.	Feb 2002	A1
20020029994	Schon	Mar 2002	A1
20020032414	Ragheb et al.	Mar 2002	A1
20020038128	Turovkiy et al.	Mar 2002	A1
20020052642	Cox et al.	May 2002	A1
20020052651	Myers et al.	May 2002	A1
20020055772	McGuckin, Jr. et al.	May 2002	A1
20020065552	Jayaraman et al.	May 2002	A1
20020065554	Streeter	May 2002	A1
20020068866	Zikorus	Jun 2002	A1
20020072794	Gabbay	Jun 2002	A1
20020099439	Schwartz et al.	Jul 2002	A1
20020111339	Klausener et al.	Aug 2002	A1
20020111647	Khairkhahan et al.	Aug 2002	A1
20020115559	Batchelor et al.	Aug 2002	A1
20020120338	Boyer et al.	Aug 2002	A1
20020123786	Gittings	Sep 2002	A1
20020123790	White et al.	Sep 2002	A1
20020123800	Taheri	Sep 2002	A1
20020123802	Snyders	Sep 2002	A1
20020129820	Ryan et al.	Sep 2002	A1
20020138131	Solovay et al.	Sep 2002	A1
20020138135	Duerig et al.	Sep 2002	A1
20020169475	Gainor et al.	Nov 2002	A1
20020173843	Peredo et al.	Nov 2002	A1
20020177890	Lenker	Nov 2002	A1
20020177894	Acosta et al.	Nov 2002	A1
20020177899	Eum	Nov 2002	A1
20020179098	Makower	Dec 2002	A1
20020183787	Wahr et al.	Dec 2002	A1
20020187288	Lim et al.	Dec 2002	A1
20020193871	Beyersdorf et al.	Dec 2002	A1
20020198563	Gainor et al.	Dec 2002	A1
20030014104	Cribier	Jan 2003	A1
20030014126	Patel et al.	Jan 2003	A1
20030018968	Avnet	Jan 2003	A1
20030023302	Moe et al.	Jan 2003	A1
20030023303	Palmaz et al.	Jan 2003	A1
20030028213	Thill et al.	Feb 2003	A1
20030028233	Vardi et al.	Feb 2003	A1
20030033009	Gabbay	Feb 2003	A1
20030036794	Ragheb et al.	Feb 2003	A1
20030040792	Gabbay	Feb 2003	A1
20030040808	Stack et al.	Feb 2003	A1
20030055483	Gumm	Mar 2003	A1
20030055492	Shaolian et al.	Mar 2003	A1
20030055496	Cai et al.	Mar 2003	A1
20030069646	Stinson	Apr 2003	A1
20030083730	Stinson	May 2003	A1
20030083741	Woo et al.	May 2003	A1
20030093071	Hauck et al.	May 2003	A1
20030093108	Avellanet et al.	May 2003	A1
20030093144	Jang	May 2003	A1
20030097172	Shalev et al.	May 2003	A1
20030109922	Peterson et al.	Jun 2003	A1
20030114913	Spenser et al.	Jun 2003	A1
20030114919	McQuiston et al.	Jun 2003	A1
20030120263	Ouriel et al.	Jun 2003	A1
20030125790	Fastovsky et al.	Jul 2003	A1
20030125791	Sequin et al.	Jul 2003	A1
20030125795	Pavcnik et al.	Jul 2003	A1
20030129751	Grikscheit	Jul 2003	A1
20030130713	Stewart et al.	Jul 2003	A1
20030130726	Thorpe et al.	Jul 2003	A1
20030135266	Chew et al.	Jul 2003	A1
20030139805	Holmberg et al.	Jul 2003	A1
20030139819	Beer et al.	Jul 2003	A1
20030144670	Pavcnik et al.	Jul 2003	A1
20030144694	Chanduszko et al.	Jul 2003	A1
20030149471	Briana et al.	Aug 2003	A1
20030153972	Helmus	Aug 2003	A1
20030153974	Spenser et al.	Aug 2003	A1
20030163190	LaFont et al.	Aug 2003	A1
20030171824	Abraham et al.	Sep 2003	A1
20030176911	Iancea et al.	Sep 2003	A1
20030176912	Chuter et al.	Sep 2003	A1
20030176914	Rabkin et al.	Sep 2003	A1
20030181968	Xie et al.	Sep 2003	A1
20030181973	Sahota	Sep 2003	A1
20030181974	Xie et al.	Sep 2003	A1
20030187500	Jansen et al.	Oct 2003	A1
20030191495	Ryan et al.	Oct 2003	A1
20030191525	Thornton	Oct 2003	A1
20030195618	Abraham et al.	Oct 2003	A1
20030199747	Michlitsch	Oct 2003	A1
20030199767	Cespedes	Oct 2003	A1
20030199768	Cespedes	Oct 2003	A1
20030206860	Bleyer et al.	Nov 2003	A1
20030208224	Broome	Nov 2003	A1
20030208254	Shortt	Nov 2003	A1
20030208261	Thorpe et al.	Nov 2003	A1
20030209835	Chun et al.	Nov 2003	A1
20030212431	Brady et al.	Nov 2003	A1
20030220683	Minasian et al.	Nov 2003	A1
20030225445	Derus	Dec 2003	A1
20030225446	Hartley	Dec 2003	A1
20030225449	Denison	Dec 2003	A1
20030236443	Cespedes	Dec 2003	A1
20030236568	Hojeibane et al.	Dec 2003	A1
20040006380	Buck et al.	Jan 2004	A1
20040015230	Moll	Jan 2004	A1
20040015232	Salazar	Jan 2004	A1
20040019374	Hojeibane et al.	Jan 2004	A1
20040024444	Moore	Feb 2004	A1
20040024447	Haverich	Feb 2004	A1
20040024452	Kruse et al.	Feb 2004	A1
20040029993	Klee et al.	Feb 2004	A1
20040034409	Heublein et al.	Feb 2004	A1
20040044401	Bales et al.	Mar 2004	A1
20040044407	Verona	Mar 2004	A1
20040047909	Ragheb	Mar 2004	A1
20040049262	Obermiller et al.	Mar 2004	A1
20040049266	Anduiza et al.	Mar 2004	A1
20040059411	Strecker	Mar 2004	A1
20040064067	Ward	Apr 2004	A1
20040073155	Laufer et al.	Apr 2004	A1
20040073230	Mulholland et al.	Apr 2004	A1
20040073238	Makower	Apr 2004	A1
20040073242	Chanduszko	Apr 2004	A1
20040073297	Rohde et al.	Apr 2004	A1
20040078053	Berg et al.	Apr 2004	A1
20040093017	Chanduszko	May 2004	A1
20040093061	Acosta et al.	May 2004	A1
20040093070	Hojeibane et al.	May 2004	A1
20040093073	Lowe et al.	May 2004	A1
20040098030	Makower et al.	May 2004	A1
20040098079	Hartley	May 2004	A1
20040098098	McGuckin et al.	May 2004	A1
20040102806	Broome et al.	May 2004	A1
20040102834	Nakano et al.	May 2004	A1
20040102855	Shank	May 2004	A1
20040106985	Jang	Jun 2004	A1
20040111145	Serino et al.	Jun 2004	A1
20040117004	Osborne et al.	Jun 2004	A1
20040117010	Houston et al.	Jun 2004	A1
20040117031	Stack et al.	Jun 2004	A1
20040122448	Levine	Jun 2004	A1
20040127981	Randert et al.	Jul 2004	A1
20040127982	Machold et al.	Jul 2004	A1
20040137042	Hiles et al.	Jul 2004	A1
20040138737	Davidson et al.	Jul 2004	A1
20040143277	Marino et al.	Jul 2004	A1
20040143291	Corcoran et al.	Jul 2004	A1
20040143292	Marino et al.	Jul 2004	A1
20040143293	Marino et al.	Jul 2004	A1
20040143294	Corcoran et al.	Jul 2004	A1
20040148000	Bilge	Jul 2004	A1
20040158331	Stack et al.	Aug 2004	A1
20040166169	Malaviya et al.	Aug 2004	A1
20040167566	Beulke et al.	Aug 2004	A1
20040167619	Case et al.	Aug 2004	A1
20040080352	Bleyer	Sep 2004	A1
20040172141	Stack et al.	Sep 2004	A1
20040176799	Chanduszko et al.	Sep 2004	A1
20040180042	Cook et al.	Sep 2004	A1
20040186558	Pavcnik	Sep 2004	A1
20040210301	Obermiller	Oct 2004	A1
20040210306	Quijano et al.	Oct 2004	A1
20040213756	Michal et al.	Oct 2004	A1
20040215333	Duran et al.	Oct 2004	A1
20040220610	Kreidler et al.	Nov 2004	A1
20040224868	Meyerhoff et al.	Nov 2004	A1
20040225344	Hoffa et al.	Nov 2004	A1
20040225348	Case et al.	Nov 2004	A1
20040225352	Osborne et al.	Nov 2004	A1
20040225356	Frater	Nov 2004	A1
20040230222	Van der Burg et al.	Nov 2004	A1
20040230287	Hartley	Nov 2004	A1
20040243216	Gregorich	Dec 2004	A1
20040243218	Schaeffer	Dec 2004	A1
20040243219	Fischer et al.	Dec 2004	A1
20040243222	Osborne et al.	Dec 2004	A1
20040249439	Richter et al.	Dec 2004	A1
20040254640	Sutherland et al.	Dec 2004	A1
20040260229	Meir	Dec 2004	A1
20040260328	Zvuloni et al.	Dec 2004	A1
20040260340	Jacobs et al.	Dec 2004	A1
20040260389	Case	Dec 2004	A1
20040260390	Sarac et al.	Dec 2004	A1
20040260393	Randert et al.	Dec 2004	A1
20040267191	Gifford, III et al.	Dec 2004	A1
20040267306	Blaeser et al.	Dec 2004	A1
20050004659	Von Oepen et al.	Jan 2005	A1
20050010248	Lafontaine	Jan 2005	A1
20050010285	Lambrecht et al.	Jan 2005	A1
20050010287	Macoviak et al.	Jan 2005	A1
20050033398	Seguin	Feb 2005	A1
20050034735	Deem et al.	Feb 2005	A1
20050038501	Moore, Jr. et al.	Feb 2005	A1
20050043708	Gleeson et al.	Feb 2005	A1
20050043759	Chanduszko	Feb 2005	A1
20050049634	Chopra	Mar 2005	A1
20050055079	Duran et al.	Mar 2005	A1
20050059923	Gamboa	Mar 2005	A1
20050060024	Lee et al.	Mar 2005	A1
20050065547	Marino et al.	Mar 2005	A1
20050065548	Marino et al.	Mar 2005	A1
20050065614	Stinson	Mar 2005	A1
20050070794	Deal et al.	Mar 2005	A1
20050070821	Deal et al.	Mar 2005	A1
20050075713	Biancucci et al.	Apr 2005	A1
20050075725	Rowe	Apr 2005	A1
20050075726	Svanidze et al.	Apr 2005	A1
20050075728	Nguyen et al.	Apr 2005	A1
20050085843	Opolski et al.	Apr 2005	A1
20050085900	Case et al.	Apr 2005	A1
20050096736	Case	Apr 2005	A1
20050092335	Bertrand	May 2005	A1
20050096734	Majercak et al.	May 2005	A1
20050096735	Hojeibane et al.	May 2005	A1
20050113686	Peckham et al.	May 2005	A1
20050113910	Paniagua	May 2005	A1
20050125032	Whisenant et al.	Jun 2005	A1
20050125050	Carter	Jun 2005	A1
20050137676	Richardson et al.	Jun 2005	A1
20050137681	Shoemaker et al.	Jun 2005	A1
20050143801	Aboul-Hosn	Jun 2005	A1
20050143806	Phillips	Jun 2005	A1
20050143807	Pavcnik	Jun 2005	A1
20050149459	Andreas et al.	Jul 2005	A1
20050154405	Kraemer et al.	Jul 2005	A1
20050163818	Sung et al.	Jul 2005	A1
20050171592	Majercak	Aug 2005	A1
20050182483	Osborne et al.	Aug 2005	A1
20050187565	Baker et al.	Aug 2005	A1
20050187614	Agnew	Aug 2005	A1
20050191496	Maschke	Sep 2005	A1
20050192626	Widomski et al.	Sep 2005	A1
20050192627	Whisenant et al.	Sep 2005	A1
20050203568	Burg et al.	Sep 2005	A1
20050216077	Mathis et al.	Sep 2005	A1
20050222661	Case et al.	Oct 2005	A1
20050228434	Amplatz et al.	Oct 2005	A1
20050228479	Pavcnik et al.	Oct 2005	A1
20050228486	Case	Oct 2005	A1
20050228495	Macoviak	Oct 2005	A1
20050228505	Cornet et al.	Oct 2005	A1
20050234509	Widomski et al.	Oct 2005	A1
20050234541	Hunt et al.	Oct 2005	A1
20050234546	Nugent et al.	Oct 2005	A1
20050240200	Bergheim	Oct 2005	A1
20050240255	Schaeffer	Oct 2005	A1
20050249772	Malaviya et al.	Nov 2005	A1
20050251201	Roue et al.	Nov 2005	A1
20050256532	Nayak et al.	Nov 2005	A1
20050261759	Lambrecht et al.	Nov 2005	A1
20050267524	Chanduszko	Dec 2005	A1
20050267526	Wahr et al.	Dec 2005	A1
20050267560	Bates	Dec 2005	A1
20050267573	Macoviak et al.	Dec 2005	A9
20050273124	Chanduszko	Dec 2005	A1
20050273153	Clerc et al.	Dec 2005	A1
20050273160	Lashinski et al.	Dec 2005	A1
20050283187	Longson	Dec 2005	A1
20050288706	Widomski et al.	Dec 2005	A1
20050288786	Chanduszko	Dec 2005	A1
20060004433	Greenberg	Jan 2006	A1
20060004436	Amarant et al.	Jan 2006	A1
20060009800	Christianson et al.	Jan 2006	A1
20060015178	Moaddeb et al.	Jan 2006	A1
20060020332	Lashinski et al.	Jan 2006	A1
20060020334	Lashinski et al.	Jan 2006	A1
20060025844	Majercak et al.	Feb 2006	A1
20060030923	Gunderson	Feb 2006	A1
20060036282	Wahr et al.	Feb 2006	A1
20060041302	Malewicz	Feb 2006	A1
20060041319	Taylor et al.	Feb 2006	A1
20060047338	Jenson et al.	Mar 2006	A1
20060052816	Bates et al.	Mar 2006	A1
20060052821	Abbott et al.	Mar 2006	A1
20060058865	Case et al.	Mar 2006	A1
20060058889	Case et al.	Mar 2006	A1
20060064152	Olson	Mar 2006	A1
20060069430	Randert et al.	Mar 2006	A9
20060074352	Case et al.	Apr 2006	A1
20060074480	Bales et al.	Apr 2006	A1
20060089708	Osse et al.	Apr 2006	A1
20060100531	Moser	May 2006	A1
20060106418	Seibold et al.	May 2006	A1
20060106420	Dolan et al.	May 2006	A1
20060106454	Osborne	May 2006	A1
20060106456	Machold et al.	May 2006	A9
20060111770	Pavcnik et al.	May 2006	A1
20060111773	Rittgers et al.	May 2006	A1
20060116548	Case et al.	Jun 2006	A1
20060116572	Case	Jun 2006	A1
20060122646	Corcoran et al.	Jun 2006	A1
20060136044	Osborne et al.	Jun 2006	A1
20060136045	Flagle et al.	Jun 2006	A1
20060155327	Briganti et al.	Jul 2006	A1
20060167468	Gabbay	Jul 2006	A1
20060173532	Flagle et al.	Aug 2006	A1
20060178729	Thielen et al.	Aug 2006	A1
20060178730	Hill et al.	Aug 2006	A1
20060178740	Stacchino et al.	Aug 2006	A1
20060184239	Andrieu et al.	Aug 2006	A1
20060195004	Jarvik	Aug 2006	A1
20060200196	Zang et al.	Sep 2006	A1
20060201996	Hodde	Sep 2006	A1
20060210597	Hiles	Sep 2006	A1
20060210603	Williams et al.	Sep 2006	A1
20060212107	Case et al.	Sep 2006	A1
20060212110	Osborne et al.	Sep 2006	A1
20060212111	Case et al.	Sep 2006	A1
20060216326	Pacetti	Sep 2006	A1
20060217760	Widomski et al.	Sep 2006	A1
20060217761	Opolski	Sep 2006	A1
20060229670	Bates	Oct 2006	A1
20060229702	Agnew	Oct 2006	A1
20060230592	Heaney	Oct 2006	A1
20060235467	DeVore	Oct 2006	A1
20060235511	Osborne	Oct 2006	A1
20060241675	Johnson et al.	Oct 2006	A1
20060241744	Beith	Oct 2006	A1
20060247762	Acosta et al.	Nov 2006	A1
20060253188	Case	Nov 2006	A1
20060259115	Case et al.	Nov 2006	A1
20060259128	Pavcnik et al.	Nov 2006	A1
20060259136	Nguyen	Nov 2006	A1
20060265053	Hunt	Nov 2006	A1
20060271030	Francis et al.	Nov 2006	A1
20060271159	Gregorich et al.	Nov 2006	A1
20060276813	Greenberg	Dec 2006	A1
20060276882	Case et al.	Dec 2006	A1
20060282157	Hill et al.	Dec 2006	A1
20060287717	Rowe et al.	Dec 2006	A1
20070016306	Dua et al.	Jan 2007	A1
20070021826	Case	Jan 2007	A1
20070027460	Case et al.	Feb 2007	A1
20070027535	Purdy et al.	Feb 2007	A1
20070027549	Godin	Feb 2007	A1
20070038291	Case	Feb 2007	A1
20070043431	Melsheimer	Feb 2007	A1
20070056346	Spenser	Mar 2007	A1
20070061002	Paul, Jr. et al.	Mar 2007	A1
20070061009	Spenser	Mar 2007	A1
20070088424	Greenberg	Apr 2007	A1
20070093887	Case et al.	Apr 2007	A1
20070100435	Case	May 2007	A1
20070106372	Osborne et al.	May 2007	A1
20070112423	Chu	May 2007	A1
20070112437	Shank	May 2007	A1
20070129738	Kraemer et al.	Jun 2007	A1
20070135826	Zaver et al.	Jun 2007	A1
20070162057	Kraemer et al.	Jul 2007	A1
20070162058	Kraemer et al.	Jul 2007	A1
20070162103	Case	Jul 2007	A1
20070167961	Kraemer et al.	Jul 2007	A1
20070173919	Maschke	Jul 2007	A1
20070185560	Roeder et al.	Aug 2007	A1
20070185565	Schwammenthal et al.	Aug 2007	A1
20070208429	Leahy	Sep 2007	A1
20070213813	Segesser et al.	Sep 2007	A1
20070225798	Gregorich	Sep 2007	A1
20070227518	Case	Oct 2007	A1
20070233237	Krivoruchko	Oct 2007	A1
20070239273	Allen	Oct 2007	A1
20070244545	Birdsall et al.	Oct 2007	A1
20070254005	Pathak	Nov 2007	A1
20070260263	Case et al.	Nov 2007	A1
20070260327	Case et al.	Nov 2007	A1
20070270931	Leanna	Nov 2007	A1
20070270932	Headley	Nov 2007	A1
20070270937	Leanna	Nov 2007	A1
20070288086	Kalmann et al.	Dec 2007	A1
20070288087	Gabbay	Dec 2007	A1
20080009934	Schneider	Jan 2008	A1
20080046071	Pavcnik	Feb 2008	A1
20080051879	Case et al.	Feb 2008	A1
20080082166	Styrc et al.	Apr 2008	A1
20080091235	Sirota	Apr 2008	A1
20080103582	Randall et al.	May 2008	A1
20080125860	Webler et al.	May 2008	A1
20080140110	Spence	Jun 2008	A1
20080200936	Kraemer et al.	Aug 2008	A1
20080200937	Kraemer et al.	Aug 2008	A1
20080208215	Kraemer et al.	Aug 2008	A1
20080221656	Hartley	Sep 2008	A1
20080228206	Kraemer et al.	Sep 2008	A1
20080228285	Kraemer et al.	Sep 2008	A1
20080243246	Ryan et al.	Oct 2008	A1
20080249538	Kraemer et al.	Oct 2008	A1
20080249609	Shanley	Oct 2008	A1
20080249612	Osborne et al.	Oct 2008	A1
20080249619	Stacchino et al.	Oct 2008	A1
20080275470	Kraemer et al.	Nov 2008	A1
20080281295	Chang	Nov 2008	A1
20080281337	Kraemer et al.	Nov 2008	A1
20080287966	Kraemer et al.	Nov 2008	A1
20080312735	Thorpe et al.	Dec 2008	A1
20090005863	Goetz et al.	Jan 2009	A1
20090018649	Jaffe et al.	Jan 2009	A1
20090062836	Kurrus	Mar 2009	A1
20090062844	Tekulve	Mar 2009	A1
20090082858	Nugent et al.	Mar 2009	A1
20090088836	Bishop et al.	Apr 2009	A1
20090099653	Suri et al.	Apr 2009	A1
20090105813	Chambers et al.	Apr 2009	A1
20090118712	Carter et al.	May 2009	A1
20090177275	Case	Jul 2009	A1
20090216321	Osborne et al.	Aug 2009	A1
20090234434	Johnson et al.	Sep 2009	A1
20090240320	Tuval et al.	Sep 2009	A1
20090248132	Bloom et al.	Oct 2009	A1
20090264991	Paul et al.	Oct 2009	A1
20090270965	Sinha et al.	Oct 2009	A1
20090287300	Dave et al.	Nov 2009	A1
20100023114	Chambers et al.	Jan 2010	A1
20100030246	Pavcnik et al.	Feb 2010	A1
20100030259	Pavcnik et al.	Feb 2010	A1
20100030314	Case et al.	Feb 2010	A1
20100057191	Pavcnik et al.	Mar 2010	A1
20100063577	Case et al.	Mar 2010	A1
20100114296	Case et al.	May 2010	A1
20100114300	Case et al.	May 2010	A1
20100121461	Sobrino-Serrano et al.	May 2010	A1
20100121462	Sobrino-Serrano et al.	May 2010	A1
20100131055	Case et al.	May 2010	A1
20100137998	Sobrino-Serrano et al.	Jun 2010	A1
20100174364	Hoffman et al.	Jul 2010	A1
20100185277	Braido et al.	Jul 2010	A1
20110022157	Essinger et al.	Jan 2011	A1
20110054497	Kraemer et al.	Mar 2011	A1
20110087198	Carter et al.	Apr 2011	A1
20110087337	Forsell	Apr 2011	A1
20110160753	Bastin	Jun 2011	A1
20110190796	Kraemer et al.	Aug 2011	A1
20110190905	Behan	Aug 2011	A1
20110202078	Kraemer et al.	Aug 2011	A1
20120078347	Braido et al.	Mar 2012	A1
20120130476	Paul et al.	May 2012	A1
20120203327	Case et al.	Aug 2012	A1
20120253446	Osborne et al.	Oct 2012	A1
20120253450	Case et al.	Oct 2012	A1
20120323306	Case et al.	Dec 2012	A1
20120330413	Pavcnik	Dec 2012	A1
20130018453	Case et al.	Jan 2013	A1
20130079867	Hoffman et al.	Mar 2013	A1
20130079868	Agnew	Mar 2013	A1
20130110254	Osborne	May 2013	A1
20130116720	Theobald et al.	May 2013	A1
20130123768	Harlan	May 2013	A1
20130226291	Pavcnik et al.	Aug 2013	A1
20130238088	Navia	Sep 2013	A1
20130289706	Schaeffer et al.	Oct 2013	A1
20140107691	Lashinski	Apr 2014	A1
20140143236	Thompson	May 2014	A1
20140155987	Paul et al.	Jun 2014	A1
20140163667	Lashinski et al.	Jun 2014	A1
20140228937	Krieger et al.	Aug 2014	A1

Foreign Referenced Citations (182)

Number	Date	Country
2003265468	Aug 2002	AU
2002248669	Oct 2002	AU
2004220576	Sep 2004	AU
2381787	Mar 2001	CA
2401996	Mar 2001	CA
2403030	Sep 2002	CA
2518867	Sep 2004	CA
2523262	Nov 2004	CA
2246526	Mar 1973	DE
19851846	May 2000	DE
10223399	Dec 2003	DE
103546	Mar 1984	EP
0350302	Jan 1990	EP
0357003	Mar 1990	EP
0386936	Sep 1990	EP
0520126	Nov 1991	EP
460428	Dec 1991	EP
0493788	Jul 1992	EP
0592410	Apr 1994	EP
0657147	Jun 1995	EP
0732089	Sep 1996	EP
0800801	Jun 1997	EP
0792627	Sep 1997	EP
0808614	Nov 1997	EP
0850607	Jul 1998	EP
0938880	Sep 1999	EP
1057460	Dec 2000	EP
1179321	Feb 2002	EP
1230901	Aug 2002	EP
1362563	Nov 2003	EP
1472996	Apr 2004	EP
1615595	Apr 2004	EP
1579886	Sep 2005	EP
1434538	Jan 2007	EP
1626681	Jul 2009	EP
1603492	Dec 2009	EP
1615593	Jan 2010	EP
2163224	Mar 2010	EP
2201911	Jun 2010	EP
1229865	Nov 2010	EP
2120795	Jul 2011	EP
2222247	Aug 2012	EP
1887980	Sep 2012	EP
1928512	Nov 2012	EP
1659992	Mar 2013	EP
2722678	Jul 1994	FR
2785174	May 2000	FR
2788217	Jul 2000	FR
2828091	Feb 2003	FR
1598111	Apr 1977	GB
2056023	Mar 1981	GB
2398245	Aug 2004	GB
6137556	Jun 1986	JP
S62-27352	Feb 1987	JP
02-307480	Dec 1990	JP
4383707	Oct 2009	JP
4589395	Dec 2010	JP
4624984	Dec 2010	JP
4940388	Mar 2012	JP
1258406	Sep 1986	SU
1271508	Nov 1986	SU
1371701	Feb 1988	SU
8302225	Jul 1983	WO
WO8501651	Apr 1985	WO
9014804	Dec 1990	WO
9117720	Nov 1991	WO
9209247	Nov 1991	WO
9217118	Oct 1992	WO
WO9407560	Apr 1994	WO
WO95277448	Oct 1995	WO
9637167	Nov 1996	WO
9640008	Dec 1996	WO
9640011	Dec 1996	WO
9724082	Jul 1997	WO
9725937	Jul 1997	WO
WO9728744	Aug 1997	WO
9732543	Sep 1997	WO
9819732	Nov 1997	WO
9822045	May 1998	WO
9825636	Jun 1998	WO
9825637	Jun 1998	WO
9826291	Jun 1998	WO
WO9827868	Jul 1998	WO
9846165	Oct 1998	WO
WO9846165	Oct 1998	WO
9858600	Dec 1998	WO
9915224	Apr 1999	WO
9933414	Jul 1999	WO
9959503	Nov 1999	WO
9962431	Dec 1999	WO
0040176	Jul 2000	WO
0042950	Jul 2000	WO
0047134	Aug 2000	WO
0064380	Nov 2000	WO
0067661	Nov 2000	WO
0067679	Nov 2000	WO
0112105	Feb 2001	WO
0119285	Mar 2001	WO
0128459	Apr 2001	WO
0130275	May 2001	WO
0149213	Jul 2001	WO
0154625	Aug 2001	WO
0156500	Aug 2001	WO
0166035	Sep 2001	WO
0166037	Sep 2001	WO
0166043	Sep 2001	WO
0166190	Sep 2001	WO
0174273	Oct 2001	WO
200183017	Nov 2001	WO
0207601	Jan 2002	WO
2002024119	Mar 2002	WO
0236045	May 2002	WO
0239888	May 2002	WO
0241764	May 2002	WO
0243620	Jun 2002	WO
0249541	Jun 2002	WO
02102284	Dec 2002	WO
03002165	Jan 2003	WO
03011195	Feb 2003	WO
03030776	Apr 2003	WO
03030782	Apr 2003	WO
03047468	Jun 2003	WO
03063733	Aug 2003	WO
03088872	Oct 2003	WO
03092554	Nov 2003	WO
03101346	Dec 2003	WO
2003101346	Dec 2003	WO
2004016200	Feb 2004	WO
2004016201	Feb 2004	WO
2004045703	Jun 2004	WO
2004080352	Sep 2004	WO
2004082528	Sep 2004	WO
2004082530	Sep 2004	WO
091449	Oct 2004	WO
2004089253	Oct 2004	WO
2004091449	Oct 2004	WO
2004093745	Nov 2004	WO
2004096100	Nov 2004	WO
2004103222	Dec 2004	WO
2004105651	Dec 2004	WO
2005011535	Feb 2005	WO
WO2005020612	Mar 2005	WO
05062931	Jul 2005	WO
2005082289	Sep 2005	WO
2005099623	Oct 2005	WO
2005099628	Oct 2005	WO
2006026325	Mar 2006	WO
2006028821	Mar 2006	WO
2006031436	Mar 2006	WO
WO2006026325	Mar 2006	WO
2006050460	May 2006	WO
2006071245	Jul 2006	WO
2006124647	Nov 2006	WO
2006125055	Nov 2006	WO
2007047945	Apr 2007	WO
2007061801	May 2007	WO
WO2007092274	Aug 2007	WO
07108857	Sep 2007	WO
2007123658	Nov 2007	WO
2007130614	Nov 2007	WO
2007139677	Dec 2007	WO
2007142935	Dec 2007	WO
2008073582	Jun 2008	WO
WO2008073582	Jun 2008	WO
2008094706	Aug 2008	WO
2008101083	Aug 2008	WO
08150529	Dec 2008	WO
2009052340	Apr 2009	WO
2009073774	Jun 2009	WO
2009088957	Jul 2009	WO
2009129481	Oct 2009	WO
2010042950	Apr 2010	WO
2010080884	Jul 2010	WO
2010091188	Aug 2010	WO
WO2010091188	Aug 2010	WO
2010099209	Sep 2010	WO
2011109450	Sep 2011	WO
WO2011109450	Sep 2011	WO
2012051489	Apr 2012	WO
2013120082	Aug 2013	WO
WO03092554	Nov 2013	WO
2014124356	Aug 2014	WO

Non-Patent Literature Citations (85)

Entry
Ali Mirnajafia, Jeremy Raymera, Michael J. Scottb, Michael S. Sacks, The effects of collagen fiber orientation on the flexural properties of pericardial heterograft biomaterials, Dec. 7, 2003, Elsevier, Biomaterials (26), 795-804.
https://www.dictionary.com/browse/viscera (Year: 2019).
European Patent Office, European Search Report & Written Opinion of the International Searching Authority, dated Apr. 18, 2012, for International Application No. PCT/US2011/056278.
Kinney, T.E., et al., “Acute, reversible tricuspid insufficiency: creation in canine model,” Am. J. Physiol. Heart Circ. Physiol. 260: H638-H641, 1991.
Bai, Yuan, et al., “Percutaneous establishment of tricuspid regugitation: an experimental model for transcatheter tricuspid valve replacement,” Chin. Med. J. 2010; 123(7), pp. 806-809.
International Search Report for PCT Application No. PCT/2008/052286, dated Jun. 17, 2008.
Written Opinion for PCT Application No. PCT/2008/052286, dated Jun. 17, 2008.
Lamba, et al., “Degradation of Polyurethanes,” Polyurethanes in Biomedical Applications, 181-204, 1998.
Matthias Chiquet, “Regulation of extracellular matrix gene expression by mechanical stress,” Matrix Biol., 417-426, 1999.
Marcy Wong, Mark Siegrist, Xuesong Cao, “Cyclic compression of articular cartilage explants is associated with progressive consolidation and altered expression pattern of extracellular matrix proteins,” Matrix Biology, 391-399, 1999.
Alan J. Grodzinsky, Marc E. Levenston, Moonsoo Jin, Eliot H. Frank, “Cartilage Tissue Remodeling in Response to Mechanical Forces,” Annual Review of Biomedical Engineering, 691-713, 2000.
V.C. Mudera, R. Pleass, M. Eastwood, R. Tarnuzzer, G. Schultz, P. Khaw, D.A. Mcgrouther, R.A. Brown, “Molecular Responses of Human Dermal Fibroblasts to Dual Cues: Contact Guidance and Mechanical Load,” Cell Motility and the Cytoskeleton, 45: 1-9, 2000.
Christof Schild, Beat Trueb, “Mechanical Stress is Required for High-Level Expression of Connective Tissue Growth Factor,” Experimental Cell Research, 274: 83-91, 2002.
European Patent Office, International Preliminary Report on Patentability, dated May 30, 2006, for International application No. PCT/US2005012421.
European Patent Office, Written Opinion of the International Searching Authority, dated Oct. 13, 2006, for International application No. PCT/US2005/012421.
European Patent Office, Later Publication of the International Search Report, dated Jul. 8, 2005 for International application No. PCT/US2005/012421.
Braun, M., et al., “Transcatheter Closure of Patent Foramen Ovale (PFO) in Patients With Paradoxical Embolism”, European Heart Journal (2004), vol. 25, pp. 424-430.
Das, Gladwin S., et al., “Experimental Atrial Septal Defect Closure With a New, Transcatheter, Self-Centering Device”, Circulation, vol. 88, No. 4, Part 1, Oct. 1993, pp. 1754-1764.
Heeschen, Christopher, et al., “Nicotine Stimulates Angiogensis and Promotes Tumor Growth and Atherosclerosis”, Nature Medicine vol. 7, No. 7, (Jul. 2001), pp. 833-839.
Johnson, Chad, et al., “Matrix Metalloproteinase-9 is Required for Adequate Angiogenic Revascularization of Ischemic Tissues”, Circulation Research, Feb. 6, 2004, No. 94, pp. 262-268.
Jux, Christian, et al., “A New Biological Matrix for Septal Occlusion”, Journal of Interventional Cardiology, vol. 16, No. 2, (2003), pp. 149-152.
King, Terry D., et al., “Secundum Atrial Septal Defect-Nonoperative Closure During Cardiac Catheterization”, JAMA, vol. 235, No. 23, Jun. 7, 1978, pp. 2506-2509.
Mullen, Michael J., et al., “BioSTAR Evaluation STudy (BEST) A Prospective, Multicenter, Phase I Clinic Trial to Evaluate the Feasibility, Efficacy, and Safety of the BioSTAR Bioabsorbable Septal Repair Implant for the Closure of Atrial-Level Shunts”, Circulation, Oct. 31, 2006, pp. 19621967.
Oguchi, M., et al., “Mucosa-adhesive water-soluble polymer film for treatment of acute radiation-induced oral mucositis”, International Journal of Radiation Oncology Biology Physics, Mar. 15, 1998, vol. 40, No. 5, p. 1033-1037.
Pavcnik, Dusan et al., “Monodisk: Device for Percutaneous Transcatheter Closure of Cardiac Septal Defects”, Cardiovasc Intervent Radio (1993) vol. 16, pp. 308-312.
Rashkind, William J., “Transcatheter Treatment of Congenital Heart Disease”, Circulation vol. 67, No. 4, Apr. 1983, pp. 711-716.
Sideris, E.B. et al., “Transvenous Atrial Septal Defect Occlusion in Piglets with a ‘Buttoned’ Double-Disk Device”, Circulation, vol. 81, No. 1, Jan. 1990, pp. 312-318.
Jux, Christian, et al., “Interventional Atrial Septal Defect Closure Using a Totally Bioresorbable Occluder Matrix”, JACC, vol. 48, No. 1 (2006), pp. 161-169.
Babic, Uros U., et al., “Transcatheter Closure of Atrial Septal Defects”, The Lancet, Sep. 1, 1990, pp. 566-567.
Bhattathiri, VN, et al., “Influence of plasma GSH level on acute radiation mucositis of the oral cavity”, International Journal of Radiation Oncology Biology Physics (1994), vol. 29, No. 2, pp. 383-386.
Complete Prosecution History, U.S. Appl. No. 13/461,260, Compiled Feb. 13, 2014.
Complete Prosecution History, U.S. Appl. No. 13/930,723, Compiled Feb. 6, 2014.
Complete Prosecution History, U.S. Pat. No. 8,475,516, Compiled Feb. 6, 2014.
Complete Prosecution History, U.S. Pat. No. 8,109,990, Compiled Feb. 6, 2014.
Lurie, Fedor Mechanism of Venous Valve Closure and Role of the Valve in Circulation: A New Concept, J Vasc Surg 2003;38:955-61. Elsevier, Amsterdam, The Netherlands.
Lurie, Fedor, The Mechanism of Venous Valve Closure in Normal Physiologic Conditions, J Vasc Surg 2002;35:713-17. Elsevier, Amsterdam, The Netherlands.
Van Bemmelen, Paul S. and Fedor Lurie, Letters to the Editor, Regarding “The Mechanism of Venous Valve Closure in Normal Physiological Conditions”, J Vasc Surg 2003; 37(1) 237-38. Elsevier, Amsterdam, The Netherlands.
Garcia-Rinaldi, Raul, Implantation of Cryopreserved Allograft Pulmonary Monocusp Patch, Tex Heart Inst J 2002;29:92-99. Texas Heart Institute, Houston, TX, USA.
Garcia-Rinaldi, Raul, Femoral Vein Valve Incompetence: Treatment with a Xenograft Monocusp Patch, J Vasc Surg 1986; 932-35. Elsevier, Amsterdam, The Netherlands.
Dana E. Perrin, James P. English, “Polycaprolactone,” Handbook of Bioabsorbable Polymers, 1997, 63-76.
Yuan et al. Geometrical Design and Finite Element Analysis on the Bioprosthetic Heart Valve. International Journal of Innovative Computing, Information and Control. vol. 3 No. 5. Oct. 2007. pp. 1289-1299. [abstract].
Office Action, Summary for U.S. Appl. No. 10/828,716, issued by the USPTO, dated Dec. 31, 2008, pp. 1-8.
Office Action, Summary for U.S. Appl. No. 12/614,878, issued by the USPTO, dated Apr. 12, 2010, pp. 1-17.
Office Action, Summary for U.S. Appl. No. 12/605,585, issued by the USPTO, dated Apr. 14, 2010, pp. 1-21.
Office Action, Summary for U.S. Appl. No. 11/586,285, issued by the USPTO, dated Jul. 16, 2009, pp. 1-9.
Brochure—Aurous Centimeter Sizing Catheters, PFVS899 p. 6.
Wai Hung Wong, David J. Mooney, “Synthesis and Properties of Biodegradable Polymers Used as Synthetic Matrices for Tissue Engineering,” I synthetic Biodegradable Polymer Scaffolds, 1997, 51-82.
Schneider (Eur.) AG v. Scimed Life Sys., 852 F. Supp. 813 (D. Minn. 1994).
European Patent Office Communication for European patent application No. 07/794571.5 dated Feb. 25, 2011.
Office Action issued by the United States Patent and Trademark Office dated Jul. 30, 2009 in U.S. Appl. No. 10/903,907.
File history of U.S. Appl. No. 12/252,253, filed Oct. 15, 2008. Inventor, Norman Jaffe. Title, Biological Valve for Venous Valve Insufficiency.
File history of U.S. Appl. No. 12/789,176, filed May 27, 2010. Inventor, Norman Jaffe. Title, Biological Valve for Venous Valve Insufficiency.
The International Bureau of WIPO, International Preliminary Report on Patentability, dated Jun. 17, 2010, for International Application No. PCT/US2008/085510.
The International Searching Authority, International Search Report and the Written Opinion, dated Mar. 26, 2009, for International Application No. PCT/US2008/085510.
The International Searching Authority, International Search Report and the Written Opinion, dated Jul. 1, 2009, for International Application No. PCT/US2009/040026.
The International Bureau of WIPO, International Preliminary Report on Patentability, dated Jun. 17, 2010, for International Application No. PCT/US2008/085495.
The International Searching Authority, International Search Report and the Written Opinion, dated Apr. 2, 2009, for International Application No. PCT/US2008/085495.
European Patent Office, The International Search Report and the Written Opinion of the International Searching Authority, dated Feb. 1, 2010, International Application No. PCT/US2009/051612.
International Preliminary Report on Patentability, The International Bureau of WIPO, dated Feb. 3, 2011, for PCT International Application No. PCT/US2009/051612.
European Search Report and Search Opinion, issued by the European Patent Office, dated Nov. 9, 2009 for Application No. 09170581.4-2320.
Extended European Search Report, mailed by the European Patent Office dated Feb. 16, 2010 for Application No. 09180708.1-2320, pp. 1-6.
Communication pursuant to Article 94(3) EPC, mailed by the European Patent Office dated Oct. 5, 2010 for Application No. 09180708.1, p. 1.
Communication pursuant to Article 94(3) EPC, mailed by the European Patent Office dated Dec. 5, 2013 for Application No. 09180708.1, pp. 1-4.
Bergan, John J., et al., “Chronic Venous Disease,” N. Engl. J. Med. 2006; 355: 488-98.
Dougal et al., “Stent Design: Implications for Restenosis,” Rev. Cardiovasc Med. 3 (suppl. 5), S16-S22 (2002).
International Preliminary Report on Patentability, for International Application No. PCT/US2008/083870, dated May 25, 2010, p. 1-7.
European Patent Office, Written Opinion of the International Searching Authority, for International application No. PCT/US2008/083870.
World Intellectual Property Organization, International Application No. PCT/US2008/083870 (Int. Pub. No. WO2009/067432) and published with the International Search Report, dated Feb. 18, 2009, p. 1-52.
Shu Chien, Song Li, John Y-J Shyy, “Effects of Mechanical Forces on Signal Transdution and Gene Expression in Endothelial Cells,” Hypertension 31, 162-169, 1998.
Stephen Badylak, Ph.D., M.D., Klod Lokini, Ph.D., Bob Tullius, M.S., Abby Simmons-Byrd, R.V.T., and Robert Morff, Ph.D., “Morphologic Study of Small Intestinal Submucosa as a Body Wall Repair Device,” Journal of Surgical Research, 103, 190-202 (2002).
Elias Brountzos, MD, Dusan Pavcnik, MD, PhD, Hans A. Timmermans, BFA, Christopher Corless, MD, PhD, Barry T. Uchida, BS, Edith S, Nihsen, BA, Manabu Nakata, MD, PhD, Maria Schoder, MD, John A. Kaufman, MD, Frederick S. Keller, MD, and Josef Rosch, MD, “Remodeling of Suspended Small Intestinal Submucosa Venous Valve: An Experimental Study in Sheep to Assess the Host Cells' Origin,” J. Vasc. Interv. Radiol, 2003 14:349-356.
Stephen S. Kim, Satoshi Kaihara, Mark S. Benvenuto, Byung-Soo Kim, David J. Mooney, and Joseph P. Vacanti, “Small Intestinal Submucosa as a Small-Caliber Venous Graft: A Novel Model for Hepatocyte Transplantation on Synthetic Biodegradable Polymer Scaffolds with Direct Access to the Portal Venous System,” Journal of Pediatric Surgery, vol. 34, No. 1 (1999) 124-128.
G.E. Sandusky, Jr., S.F. Badylak, R.J. Morff, W.D. Johnson, and G. Lantz, “Histologic Findings After In Vivo Placement of Small Intestine Submucosal Vascular Grafts and Saphenous Vein Grafts in the Carotid Artery in Dogs,” American Journal of Pathology, vol. 140, No. 2 1992, 317-324.
International Searching Authority, The International Search Report and Written Opinion of the International Searching Authority, dated May 20, 2010, for International Application No. PCT/US2010/025245.
International Search Report for corresponding international application No. PCT/US2008/052151, dated Jul. 2, 2008.
Written Opinion of the International Searching Authority for corresponding international application No. PCT/US2008/052151, dated Jul. 2, 2008.
D.K. Gilding, A.M. Reed, “Biodegradable polymers for use in surgery—polyglycolic/poly(actic acid) homo- and copolymers: 1,” Polymer, 1997, vol. 20, 1459-1464.
D.K. Gilding, “Biodegradable Polymers,” Biocompatibility of Clinical Implant Materials, Chap. 9, pp. 209-232, 1981.
Gabriel Helmlinger, Bradford C. Berk, Robert M. Nerem, “Calcium responses of endothelial cell monolayers subjected to pulsatile and steady laminar flow differ,” Am. J. Physiol. Cell Physiol., 269: C367-C375, 1995.
Matthias Chiquet, Mark Matthisson, Manuel Koch, Michael Tannheimer, Ruth Chiquet-Ehrismann, “Regulation of extracellular matrix synthesis by mechanical stress,” Biochem. Cell Biol. 74, 737-744 (1996).
Yi-Shuan Li, John Y.-J Shyy, Song Li, Jongdae Lee, Bing US, Michael Karin, Shu Chien, “The Ras-JNK Pathway Is Involved in Shear-Induced Gene Expression,” Molecular and Cellular Biology, 1996, 5947-5954.
European Patent Office, “Extended European Search Report,” for Int. App. No. 13746917.7, dated Sep. 8, 2015, pp. 1-8.
European Patent Office, “Communication pursuant to Article 94(3) EPC,” for European Application No. 13746917.7, dated Jun. 2, 2016, pp. 1-4.
European Patent Office, Extended European Search Report for Application No. 17191957.4, dated Dec. 13, 2017, pp. 1-8.
European Patent Office, Examination Report, for European application No. 17191957.4, dated Oct. 21, 2019, pp. 1-4.

Related Publications (1)

	Number	Date	Country
	20150064140 A1	Mar 2015	US

Provisional Applications (2)

	Number	Date	Country
	61597406	Feb 2012	US
	61640381	Apr 2012	US

Methods and uses of biological tissues for various stent and other medical applications

Information

Patent Number

Date Filed

Date Issued

Inventors

Original Assignees

Examiners

Agents

CPC

Field of Search

US

CPC

International Classifications

Term Extension

Abstract