Abstract: A tissue equivalent for transplantation having a three-dimensional structure which is cultured in vitro, contains cells to be transplanted and which can be transplanted into a living body after the culture, characterized by including a scaffold layer mainly culturing a scaffold constituting the three-dimensional structure and a cell layer which is localized at least in a part of the surface of the tissue equivalent for transplantation continuously with the scaffold layer and which contains the cells to be transplanted or extra cellular matrix in a larger amount than the scaffold layer. This tissue equivalent is appropriately employed as a tissue equivalent for transplantation in a relatively large size. This tissue equivalent enables realization of prompt fixation to the neighborhood of the transplanted tissue and prevention of falling off.

Abstract: The invention relates to a method for the production of a recipient-specific tissue transplant, consisting of a tissue matrix and recipient-acceptable cells populating said matrix. The transplant prepared and intended for populating is sterilized with hydrogen peroxide. Sterilization with hydrogen peroxide reliably prevents contamination while preserving the tissue base.

Abstract: A tissue graft construct for use in repairing diseased or damaged tissues is provided. The tissue graft construct comprises a matrix composition selected from the group consisting of urinary bladder submucosa and stomach submucosa, and extracts and hydrolysates thereof, added endothelial cells, and at least one additional preselected, exogenous population of cells which enhance initiation of the formation vessel-like structures in the graft construct. The preselected population of cells can be a population of non-keratinized or keratinized epithelial cells or a population of mesodermally-derived cells selected from the group consisting of fibroblasts, smooth muscle cells, skeletal muscle cells, cardiac muscle cells, multi-potential progenitor cells, pericytes, osteogenic cells, and any other suitable cell type, preferably selected based on the tissue to be repaired. Methods for enhancing the vascularization in vivo of these tissue graft constructs and for preparing these graft constructs are also provided.

Abstract: The invention is directed to a prosthetic kidney, to methods of making a prosthetic kidney and to methods of treating kidney disease with a prosthetic kidney. The prosthetic kidney comprises nephron analogs on the exterior surface and an enclosed porous membrane structure equipped with an effluent channel for collecting and draining urine from the device. The nephron analogs are prepared by implanting a device containing renal tubule analogs on the membrane structures and inducing angiogenesis to form glomeruli-like structures. The renal tubule analogs are prepared by seeding kidney cells on the porous membrane structure and culturing this composite in vitro.

Abstract: A method of increasing the rate of expansion of tissue area and volume, either in vivo or in vitro, which comprises preparing a tissue for expansion and subjecting the tissue to stretching forces, wherein the stretching forces are alternatively increased and decreased to provide alternating periods of stretch and relax cycles.

Abstract: A method for fixation of biological tissues, and bioprosthetic devices prepared by such method. The method generally comprises the steps of A) fixing the tissue, B) treating the tissue with a mixture of i) a denaturant, ii) a surfactant and iii) a crosslinking agent, C) fabricating or forming the bioprosthesis (e.g., forming the tissue and attaching any non-biological components thereto) and D) subjecting the bioprosthesis to terminal sterilization.

Abstract: The present invention relates, in general, to tissue decellularization and, in particular to a method of treating tissues, for example, heart valves, tendons and ligaments, so as to render them acellular and thereby limit mineralization and/or immunoreactivity upon implementation in vivo.

Abstract: An improved method and composition for preventing damage to tissue and/or organs during surgery and during harvesting, implanting, manufacture and manipulation of bio-prostheses therefrom. Tissue surfaces and surgical articles involved in the surgery and bioprostheses are coated with a solution of a hydrophilic, polymeric material prior to manipulation of the tissue and/or organs during surgery. The composition comprises a solution of a polymeric material having a molecular weight of about 50,000 D or above having a concentration of from about 0.01% to about 15% by weight.

Abstract: A process for preparing pliable soft tissue specimen which are resistant to cracking and devoid of viable cells includes the steps of treating native soft tissue obtained from a donor by a gradually increasing gradient of aliphatic alcohol or other suitable water miscible polar organic solvent until the last alcohol (or other solvent) solution has at least 25% by volume of the organic liquid. Thereafter, the tissue specimen is treated with a solution containing glycerol or low molecular weight (<1000 D) polyethylene glycol, and polyethylene glycol of a molecular weight between approximately 6,000 to 15,000 D and heparin. Thereafter, the tissue specimen is briefly immersed in aqueous heparin solution, frozen and lyophilized. The tissue specimen is suitable for implantation as a homograft or xenograft, with or without rehydration.

Abstract: A method of preparing a placental-derived amniotic membrane biofabric is provided. The biofabric is a dry decellularized amniotic membrane that is capable of being stored at room temperature, and subsequent to rehydration can be used for a variety of medical and/or research purposes. A laminate of said biofabric is also provided that can be shaped into complex shapes and repopulated with cells to generate both acellular and cellularized engineered tissues and organoids.

Abstract: The invention is directed to bioengineered tubular graft prostheses prepared from cleaned tissue material derived from animal sources. The bioengineered graft prostheses of the invention are prepared using methods that preserve cell compatibility, strength, and bioremodelability of the processed tissue matrix. The bioengineered graft prostheses are used for implantation, repair, or for use in a mammalian host.

Abstract: This invention is directed to prosthesis, which, when implanted into a mammalian patient, serves as a functioning replacement for a body part, or tissue structure, and will undergo controlled biodegradation occurring concomitantly with bioremodeling by the patient's living cells. The prosthesis is treated so that it is rendered non-antigenic so as not to elicit a significant humoral immune response. The prosthesis of this invention, in its various embodiments, thus has dual properties. First, it functions as a substitute body part, and second, it functions as bioremodeling template for the ingrowth of host cells.

Abstract: The present invention is directed to methods for obtaining heart valves from a donor animal that have a reduced tendency to cause inflammation when implanted into a human patient. The valves produced by this method should be less likely to undergo post-surgical degeneration.

Abstract: The invention is directed to bioengineered graft prostheses made from two or more superimposed, chemically bonded layers of processed tissue material prepared from cleaned tissue material derived from animal sources. The bioengineered graft prostheses of the invention are prepared using methods that preserve cell compatibility, strength, and bioremodelability of the processed tissue matrix. The bioengineered graft prostheses are used for implantation, repair, or for use in a mammalian host.

Abstract: The present invention relates to a method for producing a tissue-engineered organ or organ portion or specific section thereof comprising the steps of loading organoid units into a biocompatible polymer scaffold and implanting the polymer scaffold into a subject. Organs produced by this method are also encompassed by the invention. Organoid units can be derived from tissues including, but not limited to, spleen, lung, liver, kidney, pancreas, endocrine tissue, heart, esophagus, colon, stomach, gall bladder and uterus. The resulting engineered tissue can comprise spleen, lung, liver, kidney, pancreas, endocrine, cardiac muscle, esophagus, colon, stomach, gall bladder or uterus. The invention further relates to a tissue-engineered organ or organ portion or specific section thereof comprising compact tissue grown in a biocompatible polymer scaffold, wherein the tissue is derived from spleen, lung, liver, kidney, pancreas, endocrine, heart, esophagus, colon, stomach, gall bladder or uterus.

Abstract: Bioprosthetic tissues are treated by immersing or otherwise contacting fixed, unfixed or partially fixed tissue with a glutaraldehyde solution that has previously been heat-treated or pH adjusted prior to its contact with the tissue. The prior heat treating or pH adjustment of the glutaraldehyde solution causes its free aldehyde concentration to decrease by about 25% or more, preferably by as much as 50%, and allows a “stabilized” glutaraldehyde solution to be obtained at the desired concentration and pH for an optimal fixation of the tissue at high or low temperature. This treatment results in a decrease in the tissue's propensity to calcify after being implanted within the body of a human or animal patient.

Abstract: A method for treating fixed biological tissue inhibits calcification of the biological tissue following implantation thereof in a mammalian body. The method includes placing the biological tissue in contact with glutaraldehyde and then heating the glutaraldehyde. Alternatively, methods other than heating (e.g., chemical or mechanical means), for effecting polymerization of the glutaraldehyde may also be utilized. Alternatively, the tissue may be heat treated prior to fixing thereof. Alternatively, methods other than glutaraldehyde may also be used for fixing the tissue. The biological tissue may be so treated at any time prior to implantation thereof in a mammalian body.

Abstract: A method for fixation of biological tissues, and bioprosthetic devices prepared by such method. The method generally comprises the steps of A) fixing the tissue, B) treating the tissue with a mixture of i) a denaturant, ii) a surfactant and iii) a crosslinking agent, C) fabricating or forming the bioprosthesis (e.g., forming the tissue and attaching any non-biological components thereto) and D) subjecting the bioprosthesis to terminal sterilization.

Abstract: A graft prostheses (11), materials and method for implanting, transplanting, replacing, or repairing a part of a patient. The graft prosthesis includes a purified, collagen-based matrix structure removed from a submucosa tissue source. The submucosa tissue source is purified by disinfection and removal steps to deactivate and remove contaminants, thereby making the purified structure biocompatible and suitable for grafting on and/or in a patient.

Abstract: Allograft tissue prostheses, as well as tissue valves for replacement of defective heart valves and other tissue-engineered products (TEPs), are effectively sterilized by treatment with a coupling agent known to create amide linkages between amines and carboxylic acids in the presence of a protecting agent. The sterilization treatment preferably employs EDC as a water-soluble coupling agent, plus a water-soluble protecting agent which complexes with potentially reactive amine or carboxyl moieties on the biological tissue, in the optional presence of isopropanol or an equivalent alkanol. One preferred sterilization treatment process uses a buffered aqueous solution where a hydroxymonoamine buffer, such as TRIS plus ethanolamine, provides both the buffering effect and the protecting agents, effectively complexing with potentially reactive carboxyl moieties on the tissue.

Abstract: A bioprosthetic device is provided for soft tissue attachment, reinforcement, and or reconstruction. The device comprises a naturally occurring extracellular matrix portion and a three-dimensional synthetic portion. In illustrated embodiments, the naturally occurring extracellular matrix portion comprises layers of small intestine submucosa, and the three-dimensional synthetic portion comprises a foam or a three-dimensional mesh, textile, or felt.

Abstract: Disclosed herein is a method of delivering a bioactive compound to an organism that involves growing individual cells in vitro under conditions that allow the formation of an organized tissue, at least a subset of the cells containing a foreign DNA sequence which mediates the production of the bioactive compound; and implanting the organized tissue into the organism, whereby the bioactive compound is produced and delivered to the organism.

Abstract: A biological material comprising a continuous layer of cartilaginous tissue reconstituted in vitro which contains components associated with cartilage mineralization. The biological material may be cultured with a mineralizing agent to form a mineralized biological material. The mineralized biological material is characterized by having a biochemical composition and physiological organization substantially similar to the deep and contiguous calcified cartilage zones of articular cartilage found in animals in vivo. Methods for preparing the biological materials and methods of using the biological materials are described.

Abstract: A non-crosslinked, decellularized and purified mammalian tissue (e.g., bovine pericardium) having particular use as an implantable resorbable material. The material is treated by alkylating its primary amine groups in a manner sufficient to reduce the antigenicity of the tissue, permitting the treated tissue to be used in vivo and without crosslinking, and in turn, permitting it to be resorbable. The material can be used in surgical repair of soft tissue deficiencies for a certain period of time while the implant itself is gradually remodeled or absorbed by the host. Also provided are a method of preparing such a material, as well as a method of using such a material for surgical repair.

Abstract: The invention provides an article of manufacture comprising a substantially non-immunogenic soft tissue xenograft for implantation into humans. The invention further provides methods for preparing a soft tissue xenograft by removing at least a portion of a soft tissue from a non-human animal to provide a xenograft; washing the xenograft in saline and alcohol; subjecting the xenograft to cellular disruption treatment; and digesting the xenograft with a proteoglycan-depleting factor and/or glycosidase and optionally following with a capping treatment. The invention also provides an article of manufacture produced by the above-identified method of the invention. The invention further provides a soft tissue xenograft for implantation into a human including a portion of a soft tissue from a non-human animal, wherein the portion has extracellular components and substantially only dead cells. The extracellular components have reduced proteoglycan molecules.

Abstract: Acellular matrix grafts are provided with are isolated from natural sources and consist essentially of a collagen and elastin matrix which is devoid of cellular components. The grafts are useful scaffolds which promote the regeneration of muscle tissue and aid in restoring muscle function. Due to their acellular nature, the grafts lack antigenicity. As a result, the acellular matrix grafts can be isolated from autographic, allographic or xenographic tissues.

Abstract: This invention is directed to prosthesis, which, when implanted into a mammalian patient, serves as a functioning replacement for a body part, or tissue structure, and will undergo controlled biodegradation occurring concomitantly with bioremodeling by the patient's living cells. The prosthesis is treated so that it is rendered non-antigenic so as not to elicit a significant humoral immune response. The prosthesis of this invention, in its various embodiments, thus has dual properties. First, it functions as a substitute body part, and second, it functions as bioremodeling template for the ingrowth of host cells.

Abstract: A method for promoting autogenous ingrowth of damaged or diseased tissue selected from a group consisting of ligaments, tendons, muscle and cartilage, the method comprising a step of surgically repairing the damaged or diseased tissue by attachment of a tissue graft, wherein the tissue graft is formed from a segment of connective tissue protein after an acellularization process, the segment being crosslinked with genipin, its analog or derivatives. The genipin-fixed acellular tissue provides a microenvironment for tissue regeneration adapted for use as a biological implant device due to its low cytotoxicity.

Abstract: The invention provides an article of manufacture comprising a substantially non-immunogenic ligament or tendon xenograft for implantation into humans. The invention further provides a method for preparing a ligament xenograft by removing at least a portion of a ligament from a non-human animal to provide a xenograft; washing the xenograft in saline and alcohol; subjecting the xenograft to at least one treatment selected from the group consisting of exposure to ultraviolet radiation, immersion in alcohol, ozonation, freeze/thaw cycling, and optionally chemical crosslinking. In addition to or in lieu of the above treatments, the methods include a cellular disruption treatment and either digestion of the carbohydrate moieties of the xenograft with a glycosidase in a range of about 1 mU/ml to about 1000 U/ml or glycosidase digestion followed by treatment for sialylation. The invention also provides articles of manufacture produced by one or more of the above-identified methods of the invention.

Abstract: Disclosed herein is processed dermis graft for use in orthopedic surgical procedures. Specifically exemplified herein is a processed dermis graft comprising one or more bone blocks having a groove cut into the surface thereof, wherein said groove is sufficient to accommodate a fixation screw. Also disclosed is a method of processing dermis that results in a dermis derived implant suitable to replace a tendon or ligament in a recipient in need thereof. Other compositions and applications of a dermis derived implant, and methods of manutacture and use, are disclosed.

Abstract: The present invention provides a method for producing an anterior cruciate ligament ex vivo. The method comprises seeding pluripotent stem cells in a three dimensional matrix, anchoring the seeded matrix by attachment to two anchors, and culturing the cells within the matrix under conditions appropriate for cell growth and regeneration, while subjecting the matrix to one or more mechanical forces via movement of one or both of the attached anchors. Bone marrow stromal cells are preferably used as the pluripotent cells in the method. Suitable matrix materials are materials to which cells can adhere, such as a gel made from collagen type I. Suitable anchor materials are materials to which the matrix can attach, such as Goinopra coral and also demineralized bone. Some examples of tissue which can be produced include other ligaments in the body (hand, wrist, elbow, knee), tendon, cartilage, bone, muscle, and blood vessels.

Abstract: The device for conditioning an organic ligament to be implanted, in particular a ligament as a cruciate ligament replacement, is equipped with a first and with a second receiving element for receiving and tensioning the ligament at two distanced locations, wherein the first receiving element is connected to means for the periodic, and with respect to the ligament, translatoric adjustment of the first receiving element.

Abstract: A bioprosthetic device is provided for soft tissue attachment, reinforcement, and or reconstruction. The device comprises a naturally occurring extracellular matrix portion and a synthetic portion. In illustrated embodiments, the naturally occurring extracellular matrix portion comprises layers of small intestine submucosa, and the synthetic portion comprises one or more rows of fibers or mesh positioned between layers of the small intestine submucosa.

Abstract: This invention relates to a method of isolating and developing a membrane containing pluripotent autogenous stem cells of endodermal origin for the use of neo-organogenesis and neohistogenesis of various organs and tissues in mammals.

Abstract: This invention is a method for the implantation of a combination of cells or cell-microcarrier aggregates wherein one component comprises a solid implantable construct and a second component comprises an injectable formulation. For example, in one embodiment, the solid implant may be first implanted to fill the majority of the cavity receiving the implant, and then cells or cell-microcarrier aggregates in an injectable format, with or without the addition of gelling materials to promote rapid gelling in situ, may be injected into spaces surrounding the solid implant in order to secure the solid implant in the site and/or to promote rapid adherence and/or integration of the solid implant to surrounding tissues. Also contemplated in this embodiment is that the cellular composition of the injectable component may differ from that of the solid component.

Abstract: The invention provides an article of manufacture comprising a substantially non-immunogenic soft tissue xenograft for implantation into humans. The invention further provides methods for preparing a soft tissue xenograft by removing at least a portion of a soft tissue from a non-human animal to provide a xenograft; washing the xenograft in saline and alcohol; subjecting the xenograft to cellular disruption treatment; and digesting the xenograft with a proteoglycan-depleting factor and/or glycosidase and optionally following with a capping treatment. The invention also provides an article of manufacture produced by the above-identified method of the invention. The invention further provides a soft tissue xenograft for implantation into a human including a portion of a soft tissue from a non-human animal, wherein the portion has extracellular components and substantially only dead cells. The extracellular components have reduced proteoglycan molecules.

Abstract: The invention relates to a method for an vitro production of bone tissue, comprising the steps of:

Abstract: A method that allows for dry storage of bioprosthetic devices comprising a tissue component is provided. The method comprises the steps of providing a device comprising a chemically cross-linked animal tissue component; treating the tissue component with an aqueous solution comprising a biocompatible, water soluble, organic molecule comprising a plurality of carbon atoms and a plurality of hydroxyl groups for a time sufficient to allow equilibration between the fluids in the interstices of the tissue component and the aqueous solution; and then sterilizing the treated tissue component using a sterilizing gas or ionizing radiation. The present invention also relates to an implantable tissue component that can be stored dry. The tissue component is chemically-fixed and comprises within the interstices thereof a dimensional stabilizer selected from the group consisting of a polyhydric alcohol and derivatives thereof, a water soluble carbohydrate, and a water soluble gum.

Abstract: Methods are provided for preparing a replacement graft for use in repairing a damaged ligament. The methods include harvesting the graft material, shaping it accordingly, assembling the graft by attaching sutures to the ends, and packaging the graft in a sterile container.

Abstract: A process for preparing pliable soft tissue specimen which are resistant to cracking and devoid of viable cells includes the steps of treating native soft tissue obtained from a donor by a gradually increasing gradient of aliphatic alcohol or other suitable water miscible polar organic solvent until the last alcohol (or other solvent) solution has at least 25% by volume of the organic liquid. Thereafter, the tissue specimen is treated with a solution containing glycerol or low molecular weight (<1000D) polyethylene glycol, and polyethylene glycol of a molecular weight between approximately 6,000 to 15,000 D and heparin. Thereafter, the tissue specimen is briefly immersed in aqueous heparin solution, frozen and lyophilized. The tissue specimen is suitable for implantation as a homograft or xenograft, with or without rehydration.

Abstract: The present invention is directed to a transplantable cartilage matrix and a method for its in vitro production.

Abstract: It is a general object of the invention to provide a method of effecting repair or replacement or supporting a section of a body tissue. Specifically to provide an elastin or elastin-based biomaterial suitable for use as a stent, for example, a vascular stent, or as conduit replacement, as an artery, vein or a ureter replacement. The biomaterial can also be used as a stent or conduit covering or coating or lining. It is also an object of the invention to provide a method of securing an elastin or elastin-based biomaterial to an existing tissue without the use of sutures or staples.