A human acellular vessel (HAV), which may be referred to as an engineered tissue construct or “ETC”, made up of human extracellular matrix components (primarily collagen), includes a combination of mechanical and biological properties that mimic native vasculature (or other native tissue) to ensure that the HAV/ETC can withstand physiological pressures (e.g., blood pressure) and promote natural remodeling by the recipient's own cells upon implantation. Additionally, both the HAV/ETC (and similar products) and its primary packaging must be rendered sterile in order to eliminate the opportunity for a local or systemic infection resulting from the surgical procedure.
Accordingly, in some embodiments of the present disclosure, ETCs are cultivated in a bioreactor (which may also be referred to as a bioreactor bag), that, in some embodiments, is sterilized prior to use. In some embodiments, the bioreactor comprises the “housing” for the ETC throughout not only the manufacturing process, but also storage and shipment, until the bioreactor is finally opened in a surgical theater when the ETC is implanted into a patient. Accordingly, such a procedure maintains an ETC in a sterile condition from cultivation to implantation, eliminating the need for an aseptic transfer or a terminal sterilization. Advantages of this strategy, according to some embodiments, include eliminating the opportunity for microbial agents to contaminate the ETC, and thereby reducing costs associated with clean rooms, aseptic transfer equipment or terminal sterilization, as well as being ideal for process scalability.
In some embodiments, an engineered tissue construct (ETC) transport and containment method is provided and includes storing a bioreactor and an ETC contained therein within a transport package via an opening in the package, and sealing the opening.
Such embodiments, may further include one and/or another of the following (and in some embodiments, at least two of the following, and in some further embodiments, all of the following) features, structure, functionality, or clarification, leading to yet further embodiments of the present disclosure:
In some embodiments, an engineered tissue construct (ETC) transport containment method is provided, which includes optionally cultivating an ETC within an interior of a bioreactor, storing a/the bioreactor and the cultivated ETC contained therein within a transport package via an opening in the package, sealing the opening with a sealing membrane, the membrane including a plurality of pores configured to pass gaseous or vaporous molecules of a predetermined size into and/or out of the interior of the package, exposing the package and an interior thereof, including the bioreactor, to a sterilizing gas or vapor via a sterilizing means, the sterilizing means comprising an apparatus configured to expose the package and the interior thereof, including the bioreactor, to the sterilizing gas or vapor, and storing the package between approximately 2-40 degrees Celsius.
Such embodiments, may further include one and/or another of the following (and in some embodiments, at least two of the following, and in some further embodiments, all of the following) features, structure, functionality, or clarification, leading to yet further embodiments of the present disclosure:
In some embodiments, an engineered tissue construct (ETC) transport containment method is provided and comprises storing a bioreactor and an associated cultivated ETC contained therein within a transport package via an opening in the transport package, sealing the opening with a sealing membrane, the membrane including a plurality of pores configured to pass gaseous or vaporous molecules of a predetermined size into and/or out of the interior of the package, placing the sealed transport package in a chamber, providing an airflow to the chamber at an airflow rate, maintaining the chamber at a chamber pressure, optionally dehumidifying the airflow so as to dehumidify the chamber, the dehumidified airflow being provided to the chamber for a dehumidification time, after dehumidification, conditioning the airflow by first injecting a conditioning amount of a sterilizing substance into the airflow for a conditioning time, after first injecting, second injecting of a decontamination amount of the sterilizing substance into the airflow to establish (and in some embodiments, maintain) a decontamination airflow entrained with the sterilizing substance within the chamber, and exposing, within the chamber, the sealed transport package to the decontamination airflow for a decontamination time so as to decontaminate the transport packaging and the bioreactor contained herein.
Such embodiments, may further include one and/or another of the following (and in some embodiments, at least two of the following, and in some further embodiments, all of the following) features, structure, functionality, or clarification, leading to yet further embodiments of the present disclosure:
In some embodiments, a system for performing a method according to any one of the methods disclosed herein is provided.
These and other embodiments, advantages and objects thereof will become even more apparent by reference to the detailed description which follows, and corresponding figures, a brief description of which are described below.
In some embodiments, the ETC is de-cellularized prior to storing the bioreactor within the package. Accordingly, such de-cellularization can result in at least an interior of the bioreactor, as well as the ETC being substantially free from living biological organisms and viruses. In some embodiments, de-cellularization can also result in at least an interior of the bioreactor and the ETC being substantially free from prions. De-cellularization can be according to the steps, processes, and timings as specified in U.S. patent publication no. 2008/0248080, herein incorporated by reference in its entirety.
The package 104 is configured for transporting the bioreactor 102 and ETC contained therein to a surgical theater (not shown) such that the bioreactor 102 is removed from the package 104 via unsealing of the opening 106, and opened to remove the bioreactor 102 (and then the ETC from the bioreactor) for use in a surgical procedure.
The package 104 is sized to accommodate both the bioreactor 102 as whole, as well as, in some embodiments, features thereof, including, for example ports, supply tubes, and the like. Moreover, package 104 can include structure 110a and 110b, that holds up ends 102a, 102b of the bioreactor, to hold the ends (and/or ports, tubes, and the like) in place during transport. Additionally, package 104 can include one or more, and preferably, a plurality of ribs 105 that can function to at least one of add rigidity to the package 104, and support portions of the bioreactor 102 adjacent thereto.
After placing the bioreactor within the package 104, the package 104 and bioreactor 102 may be sterilized, including, in some embodiments, the interior thereof including the bioreactor 102 stored therein. Sterilizing, in some embodiments, can comprise exposing the package 102 and the interior thereof (in some embodiments, prior to sealing), including the bioreactor, to a sterilizing medium via a sterilizing means, as shown in
As shown in
In some embodiments, the process of sterilization includes dehumidification, conditioning, decontamination (with the sterilization medium), and aeration. Such steps may be conducted according to the following timing, for example, according to some embodiments; in some embodiments, the below steps can be done in a range of timings (e.g., within +/−30 15 seconds), although other timings and additional steps may be included, and other processes for sterilization my include different timings of such steps and the elimination of such steps (for example).
The sealing membrane 108 can include a plurality of microscopic pores (not shown) configured to pass gaseous or vaporous molecules of predetermined size of the sterilizing medium into and/or out of the interior of the package. In addition, according to some embodiments, the sealing membrane can be configured to be impermeable to biologics (virus, bacteria, and the like). As a result of sterilizing, the interior of the package and the exterior of the bioreactor are rendered substantially free of active biological material. In some embodiments, the package is stored between approximately 2-40 degrees Celsius until use.
While various inventive embodiments have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the function and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the inventive embodiments described herein. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, ranges, and configurations described herein are meant to be an example and that the actual parameters, dimensions, materials, ranges and configurations will depend upon the specific application or applications for which the inventive teachings is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific inventive embodiments described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of claims supported by the subject disclosure and equivalents thereto, inventive embodiments may be practiced otherwise than as specifically described and claimed. Inventive embodiments of the present disclosure are directed to each individual feature, step, function, system, article, material, kit, and/or method described herein. In addition, any combination of two or more such features, steps, systems, articles, materials, kits, and/or methods, if such features, systems, articles, materials, steps kits, and methods are not mutually inconsistent, is included within the inventive scope of the present disclosure.
Embodiments disclosed herein may also be combined with one or more features, as well as complete systems, devices and methods, to yield yet other embodiments and inventions. Moreover, some embodiments, may be distinguishable from the prior art by specifically lacking one and/or another feature disclosed in the particular prior art reference(s); i.e., claims to some embodiments may be distinguishable from the prior art by including one or more negative limitations.
Also, various inventive concepts may be embodied as one or more methods, of which examples have been provided. The acts performed as part of the method may be ordered in any suitable way. Accordingly, embodiments may be constructed in which acts are performed in an order different than illustrated, which may include performing some acts simultaneously, even though shown as sequential acts in illustrative embodiments.
Any and all references to publications or other documents, including but not limited to, patents, patent applications, articles, webpages, books, etc., presented anywhere in the present application, are herein incorporated by reference in their entirety. Moreover, all definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and/or ordinary meanings of the defined terms.
The indefinite articles “a” and “an,” as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one.”
The phrase “and/or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and/or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the “and/or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and/or B”, when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.
As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and/or” as defined above. For example, when separating items in a list, “or” or “and/or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of” or “exactly one of,” or, when used in the claims, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e. “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of” “Consisting essentially of,” when used in the claims, shall have its ordinary meaning as used in the field of patent law.
As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and/or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.
In the claims, as well as in the specification above, all transitional phrases such as “comprising,” “including,” “carrying,” “having,” “containing,” “involving,” “holding,” “composed of,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases “consisting of” and “consisting essentially of” shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.
This disclosure claims benefit of and priority to U.S. provisional patent application no. 62/946,645, filed Dec. 11, 2019, and entitled, “Systems, Devices and Methods for Engineered Tissue Construct Transport and Containment,” the entire disclosure of which is herein incorporated by reference in its entirety.
Filing Document | Filing Date | Country | Kind |
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PCT/US2020/064598 | 12/11/2020 | WO |
Number | Date | Country | |
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62946645 | Dec 2019 | US |