Patent Application
20080109034
The present invention relates, in general, to tissue fastening devices, and in particular to adhesives and adhesive systems for fastening tissue.
Tissue fastening can be either short term or long term duration. Short term duration fasteners can include a bandage, tape, removable staples, removable suture, adhesives, or absorbable stitches that are meant to provide temporary support until natural healing can occur.
Longer duration fasteners must remain in or on the body, possibly for the life of the patient. Longer duration fasteners include biocompatible implantables such as suture, staples, clips, tacks, clamps, pins, and the like. These long duration fasteners could be inserted subcutaneously in a surgical procedure and, after the patient has healed, cannot be removed without additional surgery. Longer term fasteners can provide short term and long term reinforcement for high force loads that can be 200-400% of normal forces. These high force loads could be caused by violent vomiting, coughing, and, in some cases, chronic overeating. For chronic overeaters that have undergone bariatric surgery to create a small stomach pouch, it is highly likely that a patient will “overload” the new pouch by attempting to eat the same large portions of food imbibed before the surgery.
Adhesives have been used topically as a short term fastener for wound repair. Closure Medical has developed a 2-octyl cyanoacrylate compound with a long carbon chain (eight carbons) that is biocompatible, has good bonding strength, and has received FDA approval for topical use. For short duration topical wound closure, the edges of the wound are brought together and at least one layer of the adhesive is applied along the surface of the wound line to form a barrier that holds the wound edges together. The cyanoacrylate adhesive also acts as a microbial barrier, keeping bacteria out and is eventually removed. Cyanoacrylate adhesives are described in United States Application 20040190975 by Goodman et al. which is herein incorporated by reference in its entirety.
Closure Medical is conducting an FDA clinical trial using a cyanoacrylate adhesive as an internal vascular tissue sealant and internal surgical adhesive. Some adhesives such as the cyanoacrylates, stick well to tissue, but like metallic fasteners, the fastener itself can become a local barrier to tissue regrowth through the fastener. For internal body use of surgical adhesives, the adhesive is used sparingly, not on top of the wound as in external use, but actually in the cut areas of the wound. By minimizing the glue areas across the wound, the surgeon is assured of maximum areas of tissue regrowth and minimal areas of the adhesive barrier. As the tissue regrows together and heals, the adhesive areas within the wound are encapsulated with healed tissue. Thus, internal adhesives are ideal for short term needs to hold cut tissue together so that healing can occur, and can remain as a long term fastener to provide additional strength to the healed tissue. Additionally, the adhesives can be biocompatable, bioabsorbable, and/or flexible, inside the body.
U.S. Pat. No. 6,004,333 by Sheffield Et al. discloses a prosthetic mesh with a plurality of collagen pads that can adhere the prosthetic mesh to tissue by an application of energy and pressure to the collagen pads. Energy and pressure must be applied to each and every collagen pad to create adhesion.
Consequently, a significant need exists for a long duration subcutaneous adhesive that can overcome the above-noted and other deficiencies of the prior art by providing significant attachment strength, minimize glue areas, minimize operative time, and promote tissue regrowth through the areas of adhesive application.
The invention overcomes the above-noted and other deficiencies of the prior art by providing a surgical implant for adhering two portions of tissue together. The surgical implant has at least one layer and a plurality of openings for tissue growth therethrough. A polymer adhesive is located about the implantable matrix for adhering the two portions of tissue together. The adhesive polymerizes to adhere the tissue together when the two portions of tissue are brought together.
Alternately a method of using a surgical implant to join two portions of tissue together is disclosed. The first step is providing an implantable matrix having a plurality of openings therein. The implantable matrix has at least one layer and an adhesive initiator. The second step is placing the implantable matrix onto a first portion of tissue. The third step is applying a polymer adhesive to the first portion of tissue and the implantable matrix. The fourth step is placing the second portion of tissue onto the first portion of tissue and the implantable matrix. And the last step is adhering the second portion of tissue onto the first portion of tissue and the implantable matrix by timed polymerization of the adhesive with the adhesive initiator.
And, yet another alternate method of using a surgical implant to join two portions of tissue together is disclosed. The first step of the method is providing an implantable matrix having at least one layer and a plurality of openings therein, and a polymerizable adhesive. The second step is placing the implantable matrix onto a first portion of tissue. The third step is placing the second portion of tissue onto the first portion of tissue and the implantable matrix. And the last step is adhering the second portion of tissue onto both the first portion of tissue and the implantable matrix by polymerizing the adhesive with tissue contact.
These and other objects and advantages of the present invention shall be made apparent from the accompanying drawings and the description thereof.
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention, and, together with the general description of the invention given above, and the detailed description of the embodiments given below, serve to explain the principles of the present invention.
a is a side view of
a is a side view of
a is a cross sectional view of the suture with adhesive stripes.
The following description of certain examples of the invention should not be used to limit the scope of the present invention. Other examples, features, aspects, embodiments, and advantages of the invention will become apparent to those skilled in the art from the following description, which is by way of illustration, one of the best modes contemplated for carrying out the invention. As will be realized, the invention is capable of other different and obvious aspects, all without departing from the invention. Accordingly, the drawings and descriptions should be regarded as illustrative in nature and not restrictive.
During surgery, a variety of fasteners are typically used to approximate a wound by bringing two sides of tissue together in apposition to promote healing across the wound. Adhesives can be used as a surgical fastener, but like solid fasteners such as clips, staples, sutures and the like, the surgical fasteners themselves can be a barrier to tissue regrowth and healing. The physical size of the fasteners are a barrier to healing and could create an issue to longer term treatment. Minimizing the size of the fastener is one approach to this issue, and placing adhesives sparingly across the wound site embraces this approach. Minimal adhesive placement at a plurality of application sites can reduce the size of the adhesive barrier, but can require additional surgical time to carefully place the adhesive at a plurality of locations. By strategically pre-placing the adhesive, a single part of a two part adhesive, or an adhesive initiator on a surgically implantable structure that is biocompatible such as a hex matrix or a “web”, the adhesive barrier area is minimized, the healing area is maximized and the operative time to place the adhesive or initiator is minimized.
An implantable structure for the human body must be biocompatible, and can have many different properties. By way of example, an implatable structure such as structure 26 will now be described, and the material properties are not limited to structure 26 but can apply to any other structure or shape thereof. Structure 26 can be absorbable or non-absorbable. Absorbable materials 26a for structure 26 can include but are not limited to bioabsorbables such as polylactic acid, polyglycolic acid, polyglactin, polydioxanone, polyglyconate, whey protein, cellulose gum, starch, and gelatin. If the structure 26 is absorbable, structure 26 offers an additional benefit when the surgical goal is to maximize the healing area. The absorbable material used to form structure 26 would be naturally absorbed over time, and increase the area available for tissue regrowth and healing. Non-absorbable materials 26b suitable for implants such as structure 26 can include but are not limited to metallic materials such as stainless steel, titanium, and gold, and non-metallic materials such as silk, nylon, polypropylene, braided polyester, polybutester, polyethylene, and polyetheretherketones (PEEK).
Also by way of example, structure 26 can be any durometer or hardness to make structure 26 soft and pliable or firm to hard. For sites within a patient that undergo bending or require palpitation, the soft and pliable materials could be used. For sites within a patient that may require scaffolding, a firm or hard structure would be more appropriate. Additionally, the wall structure of structure 26 can be uniform or smooth, or cellular or textured. Smooth structures could have larger cross sections and higher strength than textured structures, but textured structures could allow cellular ingrowth into the textures. Additionally, by way of example, structure 26 could include image enhancing materials such as but not limited to barium or fluorescing additives. The imaging enhancing additives can increase or enhance visibility of the structure 26 to x-rays, ultrasound, light, and the like. Additional alternate compounds can be mixed with or used to coat structure 26 such as, but not limited to those described below as alternate compounds 105.
By way of example, structure 26 is shown as a thin flexible sheet structure with a plurality of holes. Alternately, sheet structure 26 can be any single thickness such as a mesh, plate, or a honeycomb or have more than one thickness. Additionally, by way of example, structure 26 can be any one of a number of shapes or structures such as a tube, a ball, an elongated “X”, a shape folded from a flat structure, a lattice, or any one of a number of shapes that can have at least one opening 27 and have adhesives attached thereto.
For a sheet structure such as structure 26 shown in
Dollops 50 can be comprised of adhesives 100, 101, 102, 103, such as but not limited to polymerizable and/or cross-linkable materials such as a cyanoacrylate adhesive. The adhesive materials, for example, may be a monomeric (including prepolymeric) adhesive composition, a polymeric adhesive composition, or any other compound that can adhere to tissue. In embodiments, the monomer may be a 1,1-disubstituted ethylene monomer, e.g., an .alpha.-cyanoacrylate. When cross linked or polymerized, the cyanoacrylate can change from a liquid to a solid. Polymerized adhesives for example, can be formulated to be flexible to rigid. If desired, adhesives can be a single part or dual part adhesive, and/or can contain additives such as alternate compounds 105. Polymerization of the adhesives 100, 101, 102, 103 can occur from, but is not limited to, exposure to moisture or adhesion initiators 104.
Alternate compounds 105 can be attached on or about structure 26 as dollops 50, can be mixed with adhesives 100, 101, 102, 103, and could be attached to and/or combined with structure 26 in any other manner. Alternate compounds can include drugs, medicaments, contrasting agents, or any other commonly used surgical compounds, or any combination thereof. Examples of alternate compounds 105 can include, but are not limited to: adhesive initiators 104, image enhancing agents, necrosing agents, sclerosing agents, coagulants, theraputic agents, medicaments, analeptic agents, anesthesia agents, antidiuretic agents, analgesic agents, antiseptic agents, antispasmodic agents, cardiac agents, depressant agents, diuretic agents, hemostatic agents, hormonal agents, sedative agents, stimulant agents, vascular agents, time release agents, absorbable materials (see below, colorants, plasticizing agents, bulking agents, tamponade materials, thixotropic agents, antibacterial agents, buffers, catalysts, fillers, micro particles, thickeners, solvents, drugs, medicaments, natural or synthetic rubbers, stabilizers, pH modifiers, bioactive agents, cross-linking agents, chain transfer agents, fibrous reinforcements, colorants, preservatives, formaldehyde reducing or scavenging agents, flavorants, perfumes.
Adhesive initiators 104 are for polymerization and/or cross-linking of a polymerizable monomer. As used herein, a polymerization initiator is any material that causes a monomer composition applied to a substantially dry tissue (i.e., substantially in the absence of plasma or like tissue fluids) to polymerize in less than 300 seconds at ambient temperature, for example, at approximately 21-25.degree. C. Preferably, the initiator causes the monomer composition to polymerize in less than 150 seconds at ambient temperature, more preferably within 60, 90 or 130 seconds. As used herein, a polymerization rate modifier is any material that changes the rate at which a polymerizable monomer would polymerize in the absence of that material. Preferably, the rate modifier accelerates the rate of the polymerization reaction, although for particularly fast-acting monomers it may decelerate that rate.
Particular initiators 104 for particular monomers may be readily selected by one of skill in the art without undue experimentation. Control of the molecular weight distribution of the applied adhesive can be enhanced by selection of the concentration and functionality of the initiator or accelerator vis-a-vis the selected monomer. Suitable polymerization initiators and accelerators for cyanoacrylate compositions include, but are not limited to, detergent compositions; surfactants, including nonionic surfactants such as polysorbate 20 (e.g., Tween 20.™.; ICI Americas), polysorbate 80 (e.g., Tween 80.™.; ICI Americas), and poloxamers; cationic surlactants such as tetrabutylammonium bromide; anionic surfactants, including quaternary ammonium halides such as benzalkonium chloride or its pure components, and benzethonium chloride; stannous octoate (tin (II) 2-ethylhexanoate), and sodium tetradecyl sulfate; and amphoteric or zwitterionic surfactants such as dodecyldimethyl(3-sulfopropyl) ammonium hydroxide, inner salt; amines, imines, and amides, such as imidazole, tryptamine, urea, arginine and povidine; phosphines, phosphites and phosphonium salts, such as triphenylphosphine and triethyl phosphite; alcohols such as ethylene glycol; methyl gallate; inorganic bases and salts, such as sodium bisulfite, magnesium hydroxide, calcium sulfate and sodium silicate; sulfur compounds such as thiourea and polysulfides; polymeric cyclic ethers such as monensin, nonactin, crown ethers, calixarenes and polymeric epoxides; cyclic and acyclic carbonates, such as diethyl carbonate; phase transfer catalysts such as Aliquat.™. 336 (General Mills, Inc., Minneapolis, Minn.); organometallics; manganese acetylacetonate; radical initiators and radicals, such as di-t-butyl peroxide and azobisisobutyronitrile; and bioactive compounds or agents.
Alternately, the initiator may be a bioactive material, including quaternary ammonium halides such as alkylbenzyldimethylammonium chloride (benzalkonium chloride; BAC) its pure components, or mixtures thereof, especially those with an alkyl containing 6-18 carbon atoms; benzethonium chloride; and salts of sulfadiazine. Cobalt napthenate can be used as an accelerator for peroxide. Other suitable bioactive materials are disclosed in U.S. Pat. No. 5,928,611 to Leung and U.S. patent application Ser. No. 08/920,876, filed Aug. 29, 1997, Ser. No. 09/430,176 filed Oct. 29, 1999, and Ser. No. 09/430,177, filed Oct. 29, 1999, the entire disclosures of which is incorporated herein by reference.
Other examples of adhesives 100, 101, 102, 103, adhesive initiators 104, and alternate compounds 105 may be found in United States Application 20040190975 by Goodman et al. which is herein incorporated by reference in its entirety.
One embodiment of an alternate surgical implant 35 can have an absorbable plate structure or honeycomb 36 having a top surface 38, a bottom surface 39, and including a plurality of openings 37 extending therethrough. Honeycomb 36 can be any height 40 and can contain scorings or other modifications such as stress risers to induce breakup and absorption. Openings 37 can be empty for tissue growth, contain adhesives 100, 101, 102, 103, contain adhesive initiators 104, and contain alternate compounds 105, in any combination or location.
For example, as shown in
Additionally, by way of example, adhesive 100 could be applied to each surface 38, 39 of honeycomb 36, and some or all of openings 37 could be left open to provide tissue healing areas. Thus, any combination of a structure 36 with openings 37, adhesives 100, a first part 101 or a second part 102 of a two part adhesive 103, adhesive initiators 104 or an alternate compound 105 described above could be used, and the above examples are not meant to be limiting in any way. Honeycomb 36 can be easily fabricated by stamping holes in a sheet, molding, extrusion, laser or abrasive cutting, or any one of a number of commercial processes, and can be any shape described above.
Surgical implant 35 could work differently in the patient than the above surgical implant 25. For example, if honeycomb 36 of surgical implant 35 is constructed from an absorbable material listed above, and some or all openings 37 are filled with dollops 50 of adhesive 100, placement of surgical implant 35 between two layers of tissue would adhere tissue to adhesive 100. The absorbable honeycomb 36 itself could create a temporary barrier within the body to healing and regrowth, but as the absorbable material of honeycomb 36 is absorbed, the barrier to tissue growth is removed, and only dollops 50 of adhesive 100 would remain from surgical implant 35 holding the tissue together. If the dollops 50 of adhesive 100 are bioabsorbable, then full tissue healing can occur. If desired, barbs or attachment features could be included attached to honeycomb 36 and could be made from similar or dissimilar materials. Alternately, mechanical or suture ‘tacking’ could be used as an alternative to barbs.
Alternately, by way of another example, honeycomb could have many other uses other than as a tissue adhesion device. If some openings 37 of honeycomb 36 could dollops 50 of adhesives 100, 101, 102, 103, the additional openings 37 could contain dollops 50 of alternate compound such as a time release drug. The drug would be eluted slowly from the honeycomb 36 and/or, as honeycomb 36 structure dissolves. Thus, alternate surgical implant 35 combined with adhesive 100 could be used to adhere tissue, act as a drug reservoir to medicate tissue, used as a bandage, a sealing means, an attachment device for other components or devices, or any combination thereof.
For the honeycomb 36, different thickness, different absorbable materials or differing fractions of their concentration can be used to vary the time at which the contents are released. Incorporated materials or the walls themselves could dissolve at different rates associated with pH (base or acid). This could have some gastric applications.
A similar approach may be to incorporate PEGs, PLAs or dendrimers or similar materials with ligands into the walls of the honeycomb 36. When appropriate molecules or cells (cancer) come in contact with the ligands, a morphological change or dissolution of the larger macromolecule would occur to release the contents.
Releasing drugs or medicaments on demand is desirable since it could be based on the individual patient's response to a given treatment. An appealing approach is to use an excorporeal energy source to rupture or otherwise disrupt the integrity of the cells or openings 37 of honeycomb 36. It is envisioned that these would require the incorporation of special materials that are receptive to the particular form of energy. Energy could also be delivered if appropriate through natural orifices. Sources can include: laser, electromagnetic (susceptibility), and/or ultrasound.
Laser sources would require that an appropriate receptor dye be in the honeycomb material that would be highly absorptive of the energy at the laser's wavelength. Very precise control of the laser would allow very small dense packing of honeycomb cells. It may be possible to first “site” the desired cell with one wavelength or “amplitude” and then repute the wall with more energy or a different wavelength. This approach would be most appropriate were “line of sight” is available such as natural orifices and dermal applications where the honeycomb is buried under the skin such as treatment of the prostate.
Magnetic susceptibility materials have been suggested for use in oncology. Once the material is forced into a tumor, it is heated by applying an external electromagnetic field. The material could heats to ablate/kill the tumor. The same material could be incorporated in the construction of the honeycomb walls. One could image that for the cells to be ruptured early in the treatment the wall would be doped with more of the material. So they would burst first. For cells to be ruptured later in the treatment regiment, their cells would be doped with less material.
Ultrasound can be a very viable option for selective and on-demand release of drugs and medicaments from honeycomb 36. Ultrasound can be focused to a very small volume, which is the basis for diagnostic medical ultrasound. Therefore it can be very selective in terms of targeting specific cells in the honeycomb 36. The dimension of the cell could be slightly greater than the focus spot size of the ultrasound system.
One can image that an ultrasonic diagnostic unit first images the honeycomb to locate the desired cell of honeycomb 36. It is then switched to focus on the wall. The power is increased to bring the amplitude level well above the cavitation threshold. Therefore surrounding interstitial fluids will cavitate and implode near the surface of the desired cell to disrupt the cell.
Cavitation damage can be enhanced by first using a more intensity and higher frequencies to create a cavitation swarm near the surface, and then apply a lower frequency and/or lower power to sustain the cavitation for a longer period of time. These frequencies and or amplitudes are cycled at an appropriate pulse(s) repeat cycle to maximize the damage.
To enhance this approach microspheres containing fluids or gases can be incorporated into the wall material of the honeycomb 36. This has two actions. At lower diagnostic amplitudes it well make the honeycomb 36 structure easier to see. At higher amplitudes the microspheres will burst and thereby rupture the wall.
Another ultrasonic approach is to incorporate a highly ultrasonic absorptive material into the honeycomb 36. In this case the ultrasonic is used to heat the honeycomb 36 to soften and melt it. The potential temperature rise would need to be compatible with the contents of the cell.
Rectified diffusion is an ultrasonic mechanism that grows gas bubbles from gases normally held in solution. This mechanism is incorporated by introducing a dissolved gas such as CO2 to the contents (liquid) or into the wall (depending on the native strength of the wall). Therefore either the wall or the contents would expand under the influence of ultrasound and thereby rupture the cell of the honeycomb 36. In this approach the volume of cell needs to be greater than the focus volume so that one cell at at time could be burst.
The wall or the volume of the cell can be designed to be resonant at a given frequency. When that cell is impacted by an ultrasound wave of that frequency, it begins to resonant as the vibrational amplitude increases, the internal stresses increases so that cell ruptures.
An interesting concept is to first disrupt thinner adjoining walls of honeycomb 36 cells of agents that need to be mixed to be effective when released. This approach could potentially first rupture the inner wall and mix the contents, then higher intensity would be used to rupture the outer walls.
Microstreaming and shear-thinning are two ultrasonic mechanisms. These could be used to speed the dissolution of a bioabsorbable. The ultrasound would be focused on the targeted cell of the honeycomb 36 for a period of time. By these mechanisms the rate of degradation would significantly increase.
Any combination of some or all of these mechanisms are possible and may allow for a convenient system for en masse release or targeted release. Likewise other energy modalities may also provide means to release and deliver the therapeutics contained within the honeycomb 36.
a shows a small portion of an alternate embodiment of a wavy mesh structure 46 constructed from a suture 47. Suture is commonly used by surgeons as an implantable fastener and may be absorbable or non-absorbable. Suture 47 can be manufactured by an extrusion process through a spinnerette to align the long chain molecules and create a maximum strength structure. As shown in
Whereas the suture 47 is shown with all stripes 106 formed from adhesive 100, each of the stripes 101 could be a single material, or a different material or ay combination thereof. Thus, stripes 106 and can include adhesives 100, a first part 101 or a second part 102 of a two part adhesive 103, adhesive initiators 104, or alternate compounds 105. Stripes 106 can be formed neat from any of the compounds 100, 101, 102, 103, 104, 105 or combined in any proportion with plastics such as any biocompatible plastic mentioned above.
As shown, pouch 130 is made from an absorbable material and can be planted directly into a wound site such as polylactic acid, polyglycolic acid, polyglactin, polydioxanone, and polyglyconate. Additionally, pouch 130 could be made from an absorbable material that is a meltable or rapidly dissolving film such as those used for breath strips. Absorbable materials that could melt or dissolve or liquefy can include materials such as but not limited to whey protein, cellulose gums, starches, gelatins, carboxymethyl cellulose (CMC), polyethylene glycol (PEG), hyaluronic acid (HA), or other compounds. As shown, pouch 130 is a rapidly dissolving film, can be placed onto tissue, and could be dissolved by body moisture, by the application of saline, by the application of an adhesive initiator, or by the application of any one of a number of other chemicals or compounds. If desired, pouch 130 could be unsealed, sealed, or could comprise a pair of sheets 131 (not shown) that adhere to the structure 126 or dollops 50. Sheets 131 could be absorbable for implanting, or if non-absorbable, removed prior to placement into the body.
Alternately, pouch 130 could be made from one or more layers. Multi-layer pouches by way of example could be made from multiple layers with each layer performing a desired function. For example, one layer of pouch 130 could be a moisture barrier of low strength attached to a porous second layer of high strength. The combination of layers could provide a strong pouch 130 that can prevent moisture passage therethrough
Whereas the above pouch 130 is taught as being combined with structure 126, its usage is not limited to just structure 126 but can include any shape of structure described above such as structure 26, structure 36, or structure 46, and any combination of dollops 50 of adhesives 100, a first part 101 or a second part 102 of a two part adhesive 103, adhesive initiators 104 and any alternate compound 105 used therein. Additionally, any structure used in pouch 130 could be absorbable materials 26a or non-absorbable materials 26b.
And, as shown in the side view of
As shown in
A time, depending on the compounding of adhesive initiator 104, is available to the surgeon to place a second layer of tissue 172 over the first layer of tissue 171, surgical implant 26, and adhesive 100 before adhesive initiators 104 begin to set the adhesive 100.
It should be appreciated that any patent, publication, or other disclosure material, in whole or in part, that is said to be incorporated by reference herein is incorporated herein only to the extent that the incorporated material does not conflict with existing definitions, statements, or other disclosure material set forth in this disclosure. As such, and to the extent necessary, the disclosure as explicitly set forth herein supersedes any conflicting material incorporated herein by reference. Any material, or portion thereof, that is said to be incorporated by reference herein, but which conflicts with existing definitions, statements, or other disclosure material set forth herein will only be incorporated to the extent that no conflict arises between that incorporated material and the existing disclosure material.
While the present invention has been illustrated by description of several embodiments and while the illustrative embodiments have been described in considerable detail, it is not the intention of the applicant to restrict or in any way limit the scope of the appended claims to such detail. Additional advantages and modifications may readily appear to those skilled in the art.
For example, whereas several combinations of elements and examples are cited above, it would obvious to one skilled in the art to make other combinations from the elements listed above that would fall into the spirit of the present invention such as but not limited to: an absorbable ball structure containing drugs released by laser energy and sealed within a pouch.
