This application claims priority under 35 U.S.C. §119 to U.S. provisional application No. 61/491,787, filed on May 31, 2011, which is incorporated herein by reference in its entirety.
The present disclosure relates to tissue products, and more particularly, to extracellular tissue matrices made from adipose tissue.
Various tissue-derived products are used to regenerate, repair, or otherwise treat diseased or damaged tissues and organs. Such products can include tissue grafts and/or processed tissues (e.g., acellular tissue matrices from skin, intestine, or other tissues, with or without cell seeding). Such products generally have properties determined by the tissue source (i.e., tissue type and animal from which it originated) and the processing parameters used to produce the tissue products. Since tissue products are often used for surgical applications and/or tissue replacement or augmentation, the products should support tissue growth and regeneration, as desired for the selected implantation site. The present disclosure provides adipose tissue products that can allow improved tissue growth and regeneration for various applications.
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According to certain embodiments, methods for producing tissue products are provided. The methods include selecting an adipose tissue; mechanically processing the adipose tissue to reduce the tissue size; and treating the mechanically processed tissue to remove substantially all cellular material from the tissue. The processed tissue is suspended in a solution and cross-linked to produce a stable three-dimensional structure.
In addition, tissue products made by the disclosed processes are provided. The processes can include selecting an adipose tissue; mechanically processing the adipose tissue to reduce the tissue size; and treating the mechanically processed tissue to remove substantially all cellular material from the processed tissue. In addition, the processes can include suspending the processed tissue in a solution and cross-linking the tissue to produce a stable three-dimensional structure.
In addition, adipose tissue products are provided. The products can include a decellularized adipose extracellular tissue matrix, wherein the tissue matrix has been formed into a predetermined three-dimensional shape, and wherein the tissue matrix is partially cross-linked to maintain the three-dimensional shape.
Furthermore, methods of treatment are provided. The methods can comprise placing a negative pressure manifold on a wound wherein the manifold comprises a decellularized adipose extracellular tissue matrix. The tissue matrix is formed into a predetermined three-dimensional shape and is partially cross-linked to maintain the three-dimensional shape. A drape is placed over the manifold to seal the wound, and a negative pressure is applied to draw fluid through the manifold.
DESCRIPTION OF THE DRAWINGS
FIG. 1 is a flow chart illustrating a process for producing adipose tissue products, according to certain embodiments.
FIGS. 2A-2D are macroscopic images of adipose tissue products produced according to various embodiments.
FIGS. 3A-3D are hematoxylin and eosin stained sections of adipose tissue products produced according to various embodiments.
FIGS. 4A-4D are transmission electron micrographs of adipose tissue products produced according to various embodiments.
FIGS. 5A-5D are scanning electron microscope images of adipose tissue products produced according to various embodiments.
FIGS. 6A-6C are hematoxylin and eosin stained sections of adipose tissue products produced according to various embodiments after implantation in nude rats.
FIGS. 7A-7C are hematoxylin and eosin stained sections of adipose tissue products produced according to various embodiments after implantation in nude rats.
FIGS. 8A-8C are hematoxylin and eosin stained sections of adipose tissue products produced according to various embodiments after implantation in nude rats.
FIGS. 9A-9C are hematoxylin and eosin stained sections of adipose tissue products produced according to various embodiments after implantation in nude rats.
FIG. 10 shows two examples of adipose tissue-based drain manifolds. The exemplary manifolds contain grooves (left) and holes (right).
DESCRIPTION OF CERTAIN EXEMPLARY EMBODIMENTS
Reference will now be made in detail to certain exemplary embodiments according to the present disclosure, certain examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.
In this application, the use of the singular includes the plural unless specifically stated otherwise. In this application, the use of “or” means “and/or” unless stated otherwise. Furthermore, the use of the term “including”, as well as other forms, such as “includes” and “included”, is not limiting. Any range described herein will be understood to include the endpoints and all values between the endpoints.
The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. All documents, or portions of documents cited in this application, including but not limited to patents, patent applications, articles, books, and treatises, are hereby expressly incorporated by reference in their entirety for any purpose.
Various human and animal tissues can be used to produce products for treating patients. For example, various tissue products for regeneration, repair, augmentation, reinforcement, and/or treatment of human tissues that have been damaged or lost due to various diseases and/or structural damage (e.g., from trauma, surgery, atrophy, and/or long-term wear and degeneration) have been produced. Such products can include, for example, acellular tissue matrices, tissue allografts or xenografts, and/or reconstituted tissues (i.e., at least partially decellularized tissues that have been seeded with cells to produce viable materials).
A variety of tissue products have been produced for treating soft and hard tissues. For example, ALLODERM® and STRATTICE™ are two dermal acellular tissue matrices made from human and porcine dermis, respectively. Although such materials are very useful for treating certain types of conditions, materials having different biological and mechanical properties may be desirable for certain applications. For example, ALLODERM® and STRATTICE™ have been used to assist in treatment of structural defects and/or to provide support to tissues (e.g., for abdominal walls or in breast reconstruction), and their strength and biological\'properties make them well suited for such uses. However, such materials may not be ideal for regeneration, repair, replacement, and/or augmentation of adipose-containing tissues. Accordingly, the present disclosure provides tissue products that are useful for treatment of adipose-containing tissues as wells as other tissue sites. The present disclosure also provides methods for producing such tissue products.
The tissue products can include adipose tissues that have been processed to removal at least some of the cellular components. In some cases, all, or substantially all cellular material is removed, thereby leaving adipose extracellular matrix proteins. In addition, the products can be processed to remove some or all of the extracellular and/or intracellular lipids. As described further below, the extracellular matrix proteins can be further treated to produce a three-dimensional porous, or sponge-like material. In addition, to allow treatment of a selected tissue site the material can be further processed (e.g., by cross-linking) to form a stable structure.
As noted, the tissue products of the present disclosure are formed from adipose tissues. The adipose tissues can be derived from human or animal sources. For example, human adipose tissue can be obtained from cadavers. In addition, human adipose tissue could be obtained from live donors (e.g., with an autologous tissue). Adipose tissue may also be obtained from animals such as pigs, monkeys, or other sources. If animal sources are used, the tissues may be further treated to remove antigenic components such as 1,3-alpha-galactose moieties, which are present in pigs, but not humans or primates. In addition, the adipose tissue can be obtained from animals that have been genetically modified to remove antigenic moieties. See Xu, Hui. et al., “A Porcine-Derived Acellular Dermal Scaffold that Supports Soft Tissue Regeneration: Removal of Terminal Galactose-α-(1,3)-Galactose and Retention of Matrix Structure,” Tissue Engineering, Vol. 15, 1-13 (2009), which is incorporated by reference in its entirety.
An exemplary process for producing the tissue products of the present disclosure is illustrated in FIG. 1. As shown, the process generally includes obtaining adipose tissue (Step 10); mechanically processing the adipose tissue to produce small pieces (Step 12); further processing the tissue to remove substantially all cellular material and/or lipids from the tissue (Step 14); resuspending the tissue in a solution to form a porous matrix or sponge (Step 16); and cross-linking the tissue to produce a stable three-dimensional structure (Step 18). Each of these steps is explained in more detail below.
To assist in removal of the cellular components and produce a flowable mass, the tissue is first processed to produce small pieces. In various embodiments, the material is cut, ground, blended or otherwise mechanically treated to reduce the size of the tissue and/or to form a putty or flowable material. The adipose tissue can be treated using any repetitive cutting, grinding, or blending process. For example, in one embodiment, the tissue is first cut into relatively small pieces (e.g., about 2 cm×2 cm). The pieces can them be placed in an aqueous solution, which is treated with a blade grinder or similar instrument.
After processing, the tissue is then treated to removal, cellular components and lipids. The cellular material can be removed by washing the material. For example, in some embodiments, the material is further diluted with water or another solvent. The diluted material is then centrifuged, and free lipids and cell debris will flow to the top, while the extracellular matrix proteins are deposited as a pellet. The protein pellet can then be resuspended, and the washing and centrifugation can be repeated until a sufficient amount of the lipids and cellular materials are removed. In some cases, the process is repeated until substantially all cellular material and/or lipids are removed.