BIOLOGICAL BREAST IMPLANT

Abstract

This disclosure provides information on tissue products produced from adipose tissue, as well as methods for producing these tissue products. The tissue products may include acellular tissue matrices for breast treatment.

Description

BIOLOGICAL BREAST IMPLANT FIELD OF INVENTION This disclosure relates to tissue products, and more specifically to extracellular tissue matrices made from adipose tissue. BACKGROUND OF THE INVENTION Various tissue-derived products are used to regenerate, repair, or otherwise treat diseased or damaged tissues and organs. These products may include tissue grafts and / or processed tissues (e.g., acellular tissue matrices of skin, intestine, or other tissues, with or without cell seeding). These 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. Because tissue products are often used for surgical applications and / or tissue replacement or augmentation, the products must support tissue growth and regeneration as desired for the selected implantation site. This disclosure provides adipose tissue products that may enable enhanced tissue growth and regeneration for various applications, such as breast implants. BRIEF DESCRIPTION OF THE INVENTION According to certain modalities, methods are provided for producing tissue products. The methods may include selecting adipose tissue; mechanically processing the adipose tissue to reduce the tissue size; treating the mechanically processed tissue to remove substantially all cellular material from the tissue; suspending the tissue in a liquid to form a suspension; and drying the suspension in a mold to form a porous sponge. In several ways, adipose tissue is processed to control certain mechanical properties. For example, the processed tissue can be cross-linked to produce a stable three-dimensional structure. Additionally, or alternatively, the percentage of solid content in the sponge or suspension can be controlled, as discussed in further detail below. Also provided herein are fabric products made by the disclosed processes. In some modalities, tissue products 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. This document also provides a tissue product comprising a breast implant. The implant may comprise an adipose tissue matrix formed with a set MA / a / ZUZI / U14004 desired mechanical properties controlled by crosslinking and / or percentage of solids. This document also provides treatment methods comprising the steps of selecting a tissue site and implanting the tissue products disclosed herein into the tissue site. These methods may include implanting the treatment device in or near a wound or surgical site and securing at least a portion of the treatment device to the tissue in or near the treatment site. The tissue product may be implanted behind the tissue site to reinforce, reposition, or bring native tissue outward. BRIEF DESCRIPTION OF THE FIGURES Figure 1 is a flow diagram describing a process for producing an adipose tissue matrix sponge, according to certain modalities. Figure 2 is a side view of a biological breast implant that has a layered construct, according to certain modalities. Figure 3A is a perspective view of a configuration for a breast implant, which has a layered construct, according to certain modalities. Figure 3B is a perspective view of another configuration for a breast implant, which has a layered construct, according to certain modalities. Figure 30 is a perspective view of another configuration for a breast implant, which has a layered construct, according to certain modalities. Figure 4 illustrates the implantation of a system for breast surgical procedures, which includes a preformed tissue matrix, according to certain modalities. Figures 5A-5G are histological images showing the effect of EDO cross-linking on adipogenesis. Figure 6A is a bar chart showing the effect of adipose matrix solid content on compressive strength. Figure 6B is a bar chart showing the effect of adipose matrix solids content on the percentage of recovery. Figure 6C is a bar chart showing the effect of adipose matrix solids content on elasticity. Figure 6D is a bar chart showing the effect of adipose matrix solid content on the modulus. DETAILED DESCRIPTION OF THE INVENTION Reference will now be made in detail to certain example modalities in accordance with this disclosure, some examples of which are illustrated in the accompanying figures. Wherever possible, the same reference numbers will be used throughout the figures to refer to the same or similar parts. In this application, the singular includes the plural unless specifically stated otherwise. In this application, the use of “or” means “and / or” unless otherwise stated. MA / a / ZUZI / U14004 otherwise. Additionally, the use of the term “which includes”, as well as other forms such as “includes” and “included”, is not limiting. Any interval described herein shall 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 expressly incorporated by reference in their entirety for any purpose. As used herein, “tissue product” shall refer to any human or animal tissue containing an extracellular matrix protein. Tissue products may include acellular or partially decellularized tissue matrices, as well as decellularized tissue matrices that have been repopulated with exogenous cells. As used herein, the term “acellular tissue matrix” refers to an extracellular matrix derived from human or animal tissue, where the matrix retains a substantial amount of natural collagen, other proteins, proteoglycans, and glycoproteins necessary to serve as a scaffold to support tissue regeneration. Acellular tissue matrices are different from purified collagen materials, such as acid-extracted purified collagen, which are substantially depleted of other matrix proteins and do not retain the natural microstructural characteristics of the tissue matrix due to purification processes. Although referred to as “acellular tissue matrices,” it should be noted that these tissue matrices can be combined with exogenous cells, including, for example, stem cells, or cells from a patient into whom the “acellular tissue matrices” can be implanted.A “decellularized adipose tissue matrix” shall be understood to mean an adipose-based tissue from which all cells have been removed to produce an adipose extracellular matrix. “Decellularized adipose tissue matrix” may include intact matrix or matrix that has been further processed as described herein, including mechanical processing, sponge formation, and / or further processing to produce particle matrix. "Acellular" or "decellularized" tissue matrices shall be understood to refer to tissue matrices in which no cells are visible using light microscopy. Various human and animal tissues can be used to produce products for treating patients. For example, several tissue products have been produced for the 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 tear and degeneration). These products may include, for example, acellular tissue scaffolds, 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, ALLODER® and STRATTICE® (LIFECELL CORPORATION, BRANCHBURG, NJ) are two acellular dermal tissue matrices made from human and porcine dermis, respectively. While these materials are very useful for treating certain types of conditions, materials with different biological and mechanical properties may be desirable for certain applications. For example, ALLODER® and STRATTICE® have been used to assist in the treatment of structural defects and / or to provide tissue support (e.g., for abdominal walls or in breast reconstruction), and their strength and biological properties make them well-suited for these uses.However, these materials may not be ideal for the regeneration, repair, replacement, and / or augmentation of tissues containing adipose tissue when the desired outcome is the production of adipose tissue with viable adipocytes. Therefore, this disclosure provides tissue products that are useful for treating tissue defects / imperfections involving tissues containing adipose tissue. This disclosure also provides methods for producing these tissue products. Tissue products may include adipose tissue that has been processed to remove at least some of the cellular components. In some cases, all or substantially all cellular materials are removed, leaving only adipose extracellular matrix proteins. Additionally, products may be processed to remove some or all extracellular and / or intracellular lipids. However, in some cases, complete removal of extracellular and / or intracellular lipids can be detrimental to the architecture and functions of the adipose matrix. For example, adipose tissue that is chemically or enzymatically treated for an extended period may have denatured or otherwise damaged collagen, or may be depleted of proteins necessary for adipose regeneration. Consequently, in some cases, the product contains a certain level of residual lipids.The remaining lipid content may be, for example, approximately 5%, 6%, 7%, 8%, 9%, or 10% by weight of the product. As further described below, the extracellular matrix proteins may be further treated to produce a porous or sponge-like three-dimensional material, and the porous or sponge-like material may be further processed to produce an injectable product. As stated, the tissue products in this disclosure are formed from adipose tissue. Adipose tissue 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 living donors (e.g., using autologous tissue). Adipose tissue can 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 portions, which are present in pigs and other mammals but not in humans or primates. See Xu, Huí, et al., “A Porcine-Derived Acellular Dermal Scaffold that Supports Soft Tissue Regeneration: Removal of Terminal Galactose-a-(1,3)-Galactose and Retention of Matrix Structure,” Tissue Engineering, Vol. 15, 113 (2009), which is hereby incorporated by reference in its entirety.In addition, adipose tissue can be obtained from animals that have been genetically modified to remove antigenic portions. An example process for producing the tissue products of this disclosure is illustrated in Figure 1. Figure 1 provides a flow diagram illustrating the basic steps that can be used to produce a suitable adipose tissue sponge, which can then be further processed to produce injectable or implantable particles. As shown, the process may include a number of steps, but it is understood that additional or alternative steps may be added or substituted depending on the particular tissue being used, the desired application, or other factors. As shown, process 100 can generally begin at step 110, where tissue is received. The tissue can include a variety of adipose tissue types, including, for example, human or animal adipose tissue. Suitable tissue sources may include allograft, autograft, or xenograft tissue. When xenografts are used, the tissue may include adipose tissue from animals including porcine, bovine, canine, feline, domestic or wild sources, and / or any other suitable mammalian or non-mammalian adipose source. Tissue can be collected from animal sources using any desirable technique, but it is generally obtained using aseptic or sterile techniques, if possible. The tissue can be stored under chilled or frozen conditions or processed immediately to prevent any undesirable changes due to prolonged storage. After receiving the fabric, the fabric may initially be subjected to mechanical size reduction in step 120 and / or mechanical degreasing in step 130. Mechanical size reduction may include coarse or large cutting of fabric using hand blades or any other suitable grinding process. Mechanical defatting in step 130 can be important in tissue production. Specifically, to aid in lipid removal, adipose tissue may be subjected to a variety of mechanical processing conditions. For example, mechanical processing may include grinding, mixing, cutting, grating, or otherwise processing the tissue. Mechanical processing may be performed under conditions that allow for a certain degree of heating, which can help release or remove lipids. For example, mechanical processing may be performed under conditions that allow the adipose tissue to be heated to 122°F (50°C), or between 42-45°C for porcine or IVIA / a / ZUZ I / U 1^004 somewhat lower temperatures are required for human adipose tissue. The application of external heat may be insufficient to release the lipids; therefore, the heat generated during mechanical disruption may be preferred to aid in lipid removal. In some instances, the heating during mechanical processing may be a brief burst of temperature increase. This heat burst can cause liquefaction of lipids released from the fat cells ruptured by mechanical disruption, which can then lead to efficient phase separation for bulk lipid removal. For example, when porcine adipose tissue is processed, the temperature reached during this process is above 100 °F (37.7778 °C) and cannot exceed 122 °F (50 °C). The temperature range reached can be adjusted according to the origin of the adipose tissue.For example, the temperature can be further lowered to approximately 80°F (26.6667°C), 90°F (32.2222°C), 100°F (37.7778°C), 110°F (43.3333°C), or 120°F (48.8889°C) when processing less saturated tissues, such as primate tissues. Alternatively, the process can be selected to ensure that the adipose tissue reaches a minimum temperature such as 80°F (26.6667°C), 90°F (32.2222°C), 100°F (37.7778°C), 110°F (43.3333°C), or 120°F (48.8889°C). In some cases, mechanical degreasing can be achieved by mechanically processing the tissue with the addition of little or no washing fluid. For example, the tissue can be mechanically processed by milling or blending without the use of solvents. Alternatively, when tissue milling requires moisture, for example, to increase flowability or decrease viscosity, water, including pure water or saline solution, or other buffering agents, including saline or phosphate-buffered saline, can be used. In some instances, the tissue can be processed by adding a certain amount of a biocompatible solvent, such as saline solution (e.g., normal saline, phosphate-buffered saline, or solutions containing salts and / or detergents). Other solutions that facilitate cell lysis, including salts and / or detergents, may also be appropriate. After mechanical processing and lipid removal, the adipose tissue can be washed in step 140. For example, the tissue can be washed with one or more rinses using various biocompatible buffering agents. Suitable washing solutions may include saline, phosphate-buffered saline, or other suitable biocompatible physiological materials or solutions. In one example, water can be used as a rinsing agent to further disrupt the cells, after which phosphate-buffered saline, or any other suitable saline solution, can be introduced to allow the matrix proteins to return to biocompatible buffering agents. Washing can be done in conjunction with centrifugation or other separation processes. ML / a / ZUZl / Ul 4004 tissue lipids. For example, in some methods, the material is diluted with water or another solvent. The diluted material is then centrifuged, and the free lipids will flow to the top, while the extracellular matrix proteins settle as a pellet. The protein pellet can then be resuspended, and the washing and centrifugation can be repeated until a sufficient amount of lipids is removed. After any washing, adipose tissue can be treated to remove some or all of the adipose tissue cells as described in step 150. The cell removal process may include a number of suitable methods. For example, suitable methods for removing cells from adipose tissue may include treatment with detergents such as deoxycholic acid, polyethylene glycols, or other detergents at concentrations and times sufficient to disrupt the cells and / or remove cellular components. After cell removal, additional processing and / or washing steps may be incorporated, depending on the tissue used or the desired final structure, as described in step 160. For example, additional washing or treatment may be performed to remove antigenic materials such as alpha-1,3-galactose portions, which may be present in non-primate animal tissues. Furthermore, during, before, and / or after the washing steps, additional solutions or reagents may be used to process the material. For example, enzymes, detergents, and / or other agents may be used in one or more steps to further remove cellular or lipid materials, remove antigenic materials, and / or reduce bacteria or other biological load from the material. For example, one or more washing steps may be included using detergents such as sodium dodecyl sulfate or Triton to aid in lipid and cell removal.In addition, enzymes such as lipases, DNases, RNases, alpha-galactosidase, or other enzymes can be used to ensure the destruction of nuclear material, antigens from xenogeneic sources, residual cellular components, and / or viruses. Furthermore, acidic solutions and / or peroxides can be used to further aid in the removal of cellular material and the destruction of bacteria, viruses, or other potentially infectious agents. After the removal of lipids and cellular components, the material can then be formed into a porous or sponge-like material. Generally, the extracellular matrix is ​​first resuspended in an aqueous solvent to form a thick suspension-like material, as described in step 170. Sufficient solvent is used to allow the material to form a liquid mass that can be poured into a mold of the desired size and shape for the tissue product. The amount of water or solvent added can vary based on the desired porosity of the final material. In some cases, the thick suspension-like material may have a solid concentration of approximately 2% to approximately 10% by weight, preferably approximately 2% to approximately 5%.In some cases, the resuspended extracellular matrix can be mechanically treated by grinding, cutting, mixing, or other processes one or more additional times, and the treated material can be centrifuged and resuspended one or more times to further remove cellular material or lipids (if necessary) and / or to control the viscosity of the extracellular matrix. Once any additional washing and milling steps are completed, the resuspended material is placed in a container or mold to form the porous, sponge-like product, as described in step 180. Generally, the porous or sponge-like material is formed by drying the material to leave a three-dimensional matrix with a porous structure. In some methods, the material is freeze-dried. Freeze-drying can produce a three-dimensional structure that generally conforms to the shape of the mold, as shown in Figure 3. The specific freeze-drying protocol can be varied based on the solvent used, sample size, and / or to optimize processing time.A proper freeze-drying process may include cooling the material for a period of time; holding the samples at a constant temperature for a period of time and further cooling the sample to ensure complete freezing; applying a vacuum; raising the temperature and holding it for a period of time; and raising the temperature again and holding it for a period of time. The freeze-dried samples can then be removed from the freeze-dryer and packaged in nitrogen-filled aluminum bags. After the formation of a solid or sponge, the material can be optionally stabilized, as described in step 190. In some cases, stabilization may include additional processes such as crosslinking, dehydrothermal (DHT) treatment, or other suitable stabilization methods. For example, a mechanically processed tissue, when formed into a porous matrix, can generally become more of a putty or paste when implanted in a body, moistened, or placed in a solution. Consequently, the desired shape and size may be lost. In addition, the porous structure, which can be important for supporting cell adhesion, tissue growth, vascular formation, and tissue regeneration, may be lost. Therefore, the material may be further processed to stabilize its size, shape, and structure. In some methods, the material is cross-linked for stabilization. In some methods, the material is cross-linked after freeze-drying. However, the material could also be cross-linked before or during the freeze-drying process. Cross-linking can be carried out in a variety of ways. In one method, cross-linking is achieved by contacting the material with a cross-linking agent such as glutaraldehyde, genipin, carbodiimides (e.g., 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) hydrochloride), and diisocyanates. Furthermore, crosslinking can be performed by heating the material in a vacuum. For example, in some embodiments, the material can be heated to between 70 °C and 120 °C, or between 80 °C and 110 °C, or to approximately 100 °C, or any value within the specified ranges. MA / a / ZUZI / U14004 under reduced pressure or vacuum. In addition, other crosslinking processes, or combinations thereof, may be used to produce any of the disclosed products, including ultraviolet irradiation, gamma irradiation, and / or electron beam irradiation. Furthermore, a vacuum is not required, but it can reduce the crosslinking time. Lower or higher temperatures may also be used, provided that fusion of the matrix proteins does not occur and / or sufficient time is provided for crosslinking. In several ways, the cross-linking process can be controlled to produce a tissue product with desired mechanical, biological, and / or structural characteristics. For example, cross-linking can influence the overall strength of the material, and the process can be controlled to produce a desired strength. Furthermore, the degree of cross-linking can affect the product's ability to maintain a desired shape and structure (e.g., porosity) when implanted. Therefore, the amount of cross-linking can be selected to produce a stable three-dimensional shape when implanted in a body, when exposed to an aqueous environment, and / or when compressed (e.g., by surrounding tissues or materials). Excessive cross-linking can alter extracellular matrix materials. For example, excessive cross-linking can damage collagen or other extracellular matrix proteins. Damaged proteins may not support tissue regeneration when tissue products are placed in adipose tissue or other anatomical locations. Furthermore, excessive cross-linking can cause the material to be brittle or weak. Therefore, the amount of cross-linking can be controlled to produce a desired level of stability while maintaining the desired biological, mechanical, and / or structural characteristics. Examples of crosslinking processes can include contacting a freeze-dried material, produced as discussed above, with glutaraldehyde or EDO. For example, a 0.1% glutaraldehyde solution can be used, and the tissue can be immersed in the solution for approximately 18 hours, followed by extensive rinsing in water to remove the solution. Alternatively, or in combination, a dehydrothermal (DHT) process can be used. For example, a dehydrothermal process involves treating the material at 100°C and approximately 20 inches (50.8 cm) of Hg for 18 hours, followed by immersion in water. The final crosslinked tissue products can be stored in a film bag. Devices produced using the methods discussed above can have a variety of configurations. For example, Figure 2 is a side view of a biological breast implant 30 formed from an adipose tissue matrix. The implant can include a variety of shapes, contours, or projections suitable for breast implants. Furthermore, it should be appreciated that a variety of shapes can be used, including rounded, irregular, concentric spheroid, or irregular concentric 3D shapes, or custom-formed implants. For example, Figures 3A–3C illustrate example shapes for implants produced using the disclosed methods, including teardrop implants 36 (Figure 3A), irregular implants 37 (Figure 3B), and / or spherical implants 38 (Figure 30), each formed by layers 39. Devices 30, 36-38 can be produced in a variety of sizes. However, as previously mentioned, the methods described herein offer advantages by enabling the production of fat implants with sizes comparable to those of conventional breast implants or tissue expanders. For example, using the layering methods discussed herein, implants with a dimension of at least 5 cm or more can be produced. In other cases, the devices have dimensions of at least 6 cm, at least 7 cm, at least 8 cm, at least 10 cm, or more. This document also describes methods for treating a breast by implanting the tissue product. Accordingly, Figure 4 illustrates the implantation of a system for breast surgical procedures, which includes a preformed tissue matrix 32 implanted with a breast implant or tissue expander, according to certain modalities. The method may include first identifying an anatomical site within a breast 60. (As used herein, “within a breast” shall be understood to mean within the breast tissue, or within or near the tissue surrounding the breast, such as tissue just below, lateral to, or medial to the breast, or beneath surrounding tissues including, for example, muscles under the breast (pectoral), and shall also include implantation at a site where part or all of the breast has already been removed by a surgical procedure.)The site may include, for example, any suitable site that requires reconstruction, repair, augmentation, or treatment. These sites may include sites where surgical oncology procedures (mastectomy, lumpectomy) have been performed, sites where cosmetic procedures (revision or augmentation) are performed, or sites that require treatment due to disease or trauma. This document also provides treatment methods comprising the steps of selecting a tissue site and implanting the tissue products disclosed herein into the tissue site. These methods may include implanting the treatment device in or near a wound or surgical site and securing at least a portion of the treatment device to the tissue in or near the treatment site. The tissue product may be implanted behind the tissue site—in other words, deep to the tissue site—to reinforce, reposition, or bring native tissue outward. This document also provides treatment methods comprising selecting a tissue site within a breast; implanting a device within the tissue site; and allowing the tissue to grow within the acellular adipose tissue matrix. In one modality, the device comprises a synthetic breast implant or tissue expander and an acellular adipose tissue matrix surrounding the breast implant or tissue expander. The method may further include removing the breast implant or tissue expander and implanting an additional acellular adipose tissue matrix within a cavity created by the removal of the breast implant or tissue expander. The tissue products described herein can be used to treat a variety of different anatomical sites. For example, as discussed from beginning to end, the tissue products in this disclosure are produced from adipose tissue matrices and can be used for breast treatment. In some cases, the tissue products can be implanted in other sites, including, for example, tissue sites that are predominantly or significantly adipose tissue. In some cases, the tissue sites may include a breast (e.g., for augmentation, replacement of resected tissue, or placement around an implant). In addition, any other site containing adipose tissue can be selected.For example, tissue products can be used for reconstructive or cosmetic purposes in the breasts, face, buttocks, abdomen, hips, thighs, or any other area where additional fat tissue with a structure and feel similar to native fat tissue is desired. In any of these areas, the tissue can be used to reduce or eliminate wrinkles, sagging, or unwanted shapes. Example: Crosslinking effect on adipogenesis Acellular adipose matrix (AAM) sponges reduce seroma, hematoma, and scar formation, as well as promote adipogenesis. The mechanical properties of sponges must be able to adequately withstand compressive forces in the body. To improve the mechanical strength and resilience of 3D AAM sponges, the sponges were altered by chemical crosslinking (e.g., 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; EDC). However, there is often a trade-off between the biological response and the mechanical strength achieved by crosslinking. Therefore, a hairless rat model was used to evaluate the biological response to crosslinked sponges. The thick suspension of AAM was prepared, lyophilized, and crosslinked by DHT at 80°C for 24 hours. Sponges were crosslinked in either 0.016% or 0.125% EDC. N-hydroxysuccinimide (NHS) was also added in an EDC:NHS ratio of 5:3. The sponges were then terminally sterilized by electron beam with 10 kGy for non-crosslinked sponges and 15 kGy for crosslinked sponges. Sponges approximately 5 mm thick were cut with an 8 mm biopsy punch, washed in saline for 20–30 minutes, and then implanted subcutaneously in hairless rats (n = 4). At 4 weeks, the explants were cut in half, with one half fixed in 10% formalin for Masson's trichrome staining and the other half fixed in sucrose for Oil Red O staining. At 4 weeks, non-reticulated sponges exhibited cell growth, vascularization, and adipogenesis (Figures 5A and 5B). In contrast, 0.125% EDC reticulated sponges showed no adipocytes by Oil Red O staining (Figures 5E and 5F). Sponges with an intermediate amount of reticulation (0.016%) showed adipocyte levels intermediate between those found in 0.125% and non-reticulated sponges (Figures 5C and 5D). However, trichrome staining revealed extensive cell growth and vascularization in all sponge types (Figures 5A, 5C, 5E, and 5G). This suggests that adipogenesis may be slowed, not completely prevented, by EDO reticulation. In general, as EDO cross-linking increased, there was a concomitant decrease in adipogenesis, as evidenced by trichrome and Oil Red O staining. All three sponge types promoted cell growth and vascularization regardless of cross-linking conditions. Example: Effect of processing on mechanical properties AAM must have mechanical properties to adequately withstand compressive forces in the body. To improve the mechanical strength and resilience of 3D AAM sponges, the sponges were altered by (1) changing the solids content of AAM, (2) chemical crosslinking (e.g., 1-ethyl-3-(3-dimethylaminopropyl)carboamide; EDO), and (3) adding tropoelastin. The incorporation of tropoelastin, a precursor of the extracellular matrix protein elastin, can change the mechanical properties (e.g., elasticity and resilience) of AAM. The AAM suspension was prepared with either a 3% or 4% solids content in 20% PBS. The thick suspension was then lyophilized to form sponges, followed by DHT crosslinking at 80°C for 24 hours. Sponges were formed from the thick suspension with a 3% or 4% solids content, and if crosslinked with EDO, were incubated at room temperature for 4 hours in either 0.03% or 0.1% EDO in MES buffer. N-Hydroxysuccinimide (NHS) was also added to the buffer at an EDC:NHS ratio of 5:3. After crosslinking, the sponge was washed twice with PBS. The sample solids content and the amount of EDC were as follows: Sample # Sample Name 1 AAM at 3% 2 AAM at 4% 3 AAM at 3%, EDC at 0.03% 4 AAM at 4%, EDC at 0.03% 5 AAM at 3%, EDC at 0.01% 6 AAM at 4%, EDC at 0.01% In another sponge composition not shown here, 10 mg / ml of tropoelastin in PBS was crosslinked with 10 mM bis(sulfosuccinimidyl)suberate (BS3) at 37°C for 18 hours. The tropoelastin hydrogel was then cut and incorporated into the thick AAM suspension to a final concentration of 1%. The tropoelastin and thick AAM suspension were then lyophilized to form sponges and crosslinked as described above. Compression tests were performed on sponges hydrated with PBS to evaluate compressive strength at 50% deformation, the percentage of shape recovery after compression, and the modulus. Here, the modulus is defined as the slope of the linear region of the force-displacement curve. Tensile tests were performed to evaluate elasticity using sponge strips that were hydrated with PBS and then gently squeezed to remove excess liquid. There was a general linear trend for compressive strength, elasticity, and modulus as the percentage of EDC increased (Figures 6A, 6C, and 6D). For each EDC crosslinking condition, the 4% AAM sponge was stronger than its 3% counterpart. The 4% AAM sponge with 0.1% EDC (sample 6) exhibited the highest strength for these parameters. Figure 6B shows that the 0.03% and 0.1% EDC crosslinking conditions similarly improved shape recovery by an average of 7.2% over the non-crosslinked versions. Increasing the solids content from 3% to 4% improved the mechanical strength of the sponges. EDC crosslinking further enhanced mechanical strength, with the highest EDC concentration (0.1%) resulting in stronger sponges than the lowest EDC concentration (0.03%).

Claims

1. A method for producing a tissue product, comprising the steps of: selecting adipose tissue; treating the tissue to remove substantially all cellular material from the tissue; suspending the tissue in a liquid to form a suspension with 2-4% by weight of solid content; and freezing and drying the suspension to form a porous sponge.

2. The method of claim 1, further comprising cross-linking the porous sponge.

3. The method of claim 2, wherein the crosslinking is carried out using a dehydrothermal process.

4. The method according to claim 3, further comprising performing a chemical crosslinking step.

5. The method of claim 1, wherein the porous sponge comprises a desired thickness at least in the thickest part of the sponge, the desired thickness exceeding 10.0 cm.

6. The method of claim 1, further comprising adding the suspension to a mold.

7. The method of claim 6, wherein the mold is in the shape of a round or teardrop-shaped breast implant.

8. The method of claim 4, wherein the chemical crosslinking step includes at least one of glutaraldehyde, genepin, carbodiimides, and diisocyanates.

9. The method of claim 4, wherein the crosslinking includes heating the porous sponge.

10. The method of claim 9, wherein the porous sponge is heated in a vacuum.

11. The method of claim 10, wherein the porous sponge is heated to a range of 70°C to 120°C.

12. The method of claim 4, wherein the porous sponge is cross-linked such that the material maintains a stable three-dimensional structure when in contact with an aqueous environment.

13. The method of claim 12, wherein the aqueous environment is a mammalian body.

14. A tissue product, comprising: a breast implant, the implant comprising an acellular adipose tissue matrix construct including an acellular adipose tissue matrix of particles that has been homogenized to form a suspension, dried, and stabilized, and wherein the implant measures at least 5 cm in at least one dimension.

15. The tissue product of claim 14, wherein the implant measures at least 8 cm in at least one dimension.

16. The tissue product of claim 14, wherein the implant is in the form of a rounded breast implant.

17. The tissue product of claim 14, wherein the implant is in the form of a teardrop-shaped breast implant.

18. The fabric product of claim 14, wherein the suspension comprises 24% by weight of solid content.

19. The tissue product of claim 14, wherein the implant is produced by a process comprising: selecting adipose tissue; treating the tissue to remove substantially all cellular material from the tissue; suspending the tissue in a liquid to form a suspension with 2-4% by weight of solid content; and freezing and drying the suspension to form a porous sponge.

20. The fabric product of claim 14, wherein the suspension is stabilized by crosslinking.

21. The fabric product of claim 20, wherein the crosslinking is carried out using a dehydrothermal process.

22. The fabric product according to claim 21, further comprising performing a chemical crosslinking step.

23. The tissue product of claim 22, wherein the chemical crosslinking step includes at least one of glutaraldehyde, genepin, carbodiimides, and diisocyanates.

24. The fabric product of claim 22, wherein the crosslinking includes heating.

25. The fabric product of claim 24, further comprising heating in a vacuum.

26. The fabric product of claim 25, further comprising heating to a range of 70°C to 120°C.

27. The tissue product of claim 22, wherein the suspension is cross-linked such that the implant maintains a stable three-dimensional structure when in contact with an aqueous environment.

28. The fabric product of claim 27, wherein the aqueous environment is a mammalian body.

29. A treatment method, comprising the steps of: ML / a / ZUZl / Ul 4004 s selecting an anatomical site that needs reconstruction, repair, augmentation, or treatment; implanting a tissue product in or near the anatomical site, wherein the tissue product comprises a breast implant, the implant comprising an acellular adipose tissue matrix construct including an acellular adipose tissue matrix of particles that has been homogenized to form a suspension, dried, and stabilized, and wherein the implant measures at least 5 cm in at least one dimension; and securing at least a portion of the tissue product in or near the anatomical site.

30. The method of claim 29, wherein the anatomical site is a breast.

31. The method of claim 29, wherein the anatomical site is a face, buttock, abdomen, hip, or thigh.

32. The method of claim 29, wherein a mastectomy, lumpectomy, or cosmetic procedure has been performed on the anatomical site.

33. The method of claim 29, wherein the anatomical site is in need of treatment due to disease or trauma.

34. The method of claim 29, wherein the tissue product is implanted deep into the anatomical site to reinforce, reposition, or bring native tissue outward.

35. The method according to claim 29, further comprising allowing native tissue to grow within the tissue product.

36. The method according to claim 29, further comprising: removing the tissue product; and implanting a second tissue product within the cavity formed by the removal of the tissue product.