Abstract: Provided herein are skin substitutes suitable for use in a living subject for purpose of repairing damaged tissues, methods of producing the skin substitutes and their uses. A biocomposite membrane comprising poly(?-caprolactone) (PCL) and at least one material selected from collagen and gelatin is provided. In one embodiment, the biocomposite is a 2-component membrane of PCL and gelatin. In another embodiment, the biocomposite is a 3-component membrane of PCL, collagen and gelatin. The bio-composite membrane may be used directly in vivo as a wound dressing, or as a support for cell growth on each side of the membrane to produce an in vitro cultivated artificial skin for future in vivo and/or in vitro applications.

Abstract: A process for hydrolyzing products with enzymatic activity remaining in peptone solutions after mucosa hydrolysis is provided along with a process for preserving mucosa tissue. Broadly, the processes are carried out by hydrolyzing mucosa tissue according to conventional heparin manufacturing processes wherein an excess quantity of proteolytic enzymes is used. The resulting peptone solution is then contacted with proteins or protein-containing materials in order to hydrolyze the proteins. In another embodiment, mucosa tissue is preserved by mixing it with a preserving agent selected from the group consisting of hydrogen peroxide and phosphoric acid. The product preserved by hydrogen peroxide is low in ash, stable for at least a week, and has a reduced odor.

Abstract: The present invention relates generally to compositions for wound closure. More specifically, the present invention provides human skin equivalents engineered to express exogenous polypeptides (e.g., antimicrobial polypeptides and keratinocyte growth factor 2) and compositions and methods for making human skin equivalents engineered to express exogenous polypeptides. In addition, the present invention provides methods for treatment of wounds with human skin equivalents engineered to express exogenous polypeptides.

Abstract: Micro-organ cultures which include isolated populations of cells having specific characteristics are described. Salient features of the subject micro-organ cultures include the ability to be maintained in culture for relatively long periods of time, as well as the preservation of an organ microarchitecture which facilitates, for example, cell-cell and cell-matrix interactions analogous to those occurring in the source organ. The micro-organ cultures of the invention can be used in methods for delivering gene products to recipient subjects, for identifying cell proliferative and cell differentiating agents, and identification and isolation of progenitor and stem cells. In addition, the micro-organ cultures of the present invention can be used in methods for identifying inhibitors of cell proliferation, cell differentiation and viral infectivity. In other embodiments, the micro-organ cultures can be used for transplantation.

Abstract: Micro-organ cultures which include isolated populations of cells having specific characteristics are described. Salient features of the subject micro-organ cultures include the ability to be maintained in culture for relatively long periods of time, as well as the preservation of an organ microarchitecture which facilitates, for example, cell-cell and cell-matrix interactions analogous to those occurring in the source organ. The micro-organ cultures of the invention can be used in methods for delivering gene products to recipient subjects, for identifying cell proliferative and cell differentiating agents, and identification and isolation of progenitor and stem cells. In addition, the micro-organ cultures of the to present invention can be used in methods for identifying inhibitors of cell proliferation, cell differentiation and viral infectivity. In other embodiments, the micro-organ cultures can be used for transplantation.

Abstract: The present invention relates to an immortalized human neural precursor cell line, NGC-407. The cell line has been established from human foetal tissue. The cell line has been immortalized using a retroviral vector containing the v-myc oncogene. The cell line is a neural progenitor cell line capable of differentiating into to astrocytes and neurons including dopaminergic neurons. NGC-407 cells are capable of migrating to glioblastoma tumours implanted into rat brains and form gap junctions with the tumour cells. NGC-407 cells expressing a suicide gene can be be used for delivering activated prodrugs in the form of activated nucleoside analogs to tumours.

Abstract: Embodiments of the present invention provide Dermal Micro-organs (DMOs), methods and apparatuses for producing the same. Some embodiments of the invention provide a DMO including a plurality of dermal components, which substantially retain the micro-architecture and three dimensional structure of the dermal tissue from which they are derived, having dimensions selected so as to allow passive diffusion of adequate nutrients and gases to cells of the DMO and diffusion of cellular waste out of the cells so as to minimize cellular toxicity and concomitant death due to insufficient nutrition and accumulation of waste in the DMO. Some embodiments of the invention provide methods and apparatuses for harvesting the DMO. An apparatus for harvesting the DMO may include, according to some exemplary embodiments, a support configuration to support a skin-related tissue structure from which the DMO is to be harvested, and a cutting tool able to separate the DMO from the skin-related tissue structure.

Abstract: The present invention provides a liver preservation solution containing trehalose and dibutyryl-cAMP. The content of nitroglycerin in the preservation solution is preferably lower than 0.44 mM. In the liver preservation solution of the present invention, since the toxicity due to nitroglycerin, which is observed during liver preservation, has been improved, liver transplantation can be performed with a high engrafted rate.

Abstract: Mice comprising a human p16 transgene operably linked to an inducible promoter and capable of controlled expression of p16 are provided. Also provided are cells, tissues, and organs obtainable from such mice, and methods for producing p16 transgenic mice.

Abstract: Described is a protective solution for avoiding ischemic, storage or ischemia/reperfusion to organs, or to isolated cell systems, or to tissue components after perfusion, surgery, transplantation, or cryopreservation and subsequent reperfusion, which contains alkali ions, and if need be also alkaline earth ions as the electrolyte, a buffer e.g. on a histidine derivation basis, as well as a polyol and/or a saccharide, has an osmolarity of about 290 mosm/l to about 350 mosm/l, as well as a pH value of about 6.8 to about 7.4, and to which hydroxamic acid, and/or one or more hydroxamic acid derivatives are added.

Abstract: A method for processing and preserving an acellular collagen-based tissue matrix for transplantation is disclosed. The method includes the steps of processing biological tissues with a stabilizing solution to reduce procurement damage, treatment with a processing solution to remove cells, treatment with a cryoprotectant solution followed by freezing, drying, storage and rehydration under conditions that preclude functionally significant damage and reconstitution with viable cells.

Abstract: A method for rapid, in-situ flushing of organs of a non-heart beating donor, and solutions for carrying out the flushing, are provided. The method initiates organ preservation, and the solutions are formulated to counteract basic mechanisms of ischemic cell injury, and to activate known biochemical survival pathways in the cell. Viability of the organ for transplant is thus maintained.

Abstract: Reactors that allow mixing and gasification by converting the entire floor of the reactor vessel to a sparge filter is described.

Abstract: A graft tensioning device comprising a basin capable of containing a fluid, a heating element capable of heating the fluid to an appropriate temperature, a tray disposed within the basin, and a graft holding fixture for maintaining a tissue graft in tension, permanently or removably secured to the tray, wherein the graft holding fixture and tissue graft may be submersed within the fluid. The device may further comprise a base, a shelf and/or a cover. The device may be reusable, disposable or some combination thereof.

Abstract: Fluorophosphate containing an ethylene-tetrafluoroethylene moiety of formula (I) or (II): (A)w-P(O)(O?M+)3-w??(I) or wherein A is Rf—(CH2)k—[(CF2CF2)y—(CH2CH2)z]mO and contains from about 8 to about 22 carbon atoms; Rf is CnF2n+1; n and k are each independently 1 to about 6; y, z, and m are each independently 1, 2, 3, or mixture thereof; w is 1 or 2 or a mixture thereof; and M is hydrogen, ammonium ion, an alkali metal ion, or an alkanolammonium ion, said fluorophosphate useful as a surfactant for altering the surface behavior of a liquid by addition thereto, and for providing surface effects to a substrate treated with a composition containing the fluorophosphate.

Abstract: In the transplant of a living organism tissue, such as a heart valve, taken from an animal, etc. into a human body, a cell removing solution for removing original cells from the living organism tissue is provided with flow approximately equal to the bloodstream of transplant recipient living body, and the living organism tissue is placed in the flow so as to effect immersion of the living organism tissue in the cell removing solution. In the immersion, it is preferred that the living organism tissue placed in the cell removing solution, while being rotated, be irradiated with microwave. As a result, original cells can be removed from the living organism tissue uniformly and reliably, so that the biocompatibility of living organism tissue after transplant can be enhanced.

Abstract: Hybrid synthetic grafts and embodiments of systems and methods for producing hybrid vascular grafts that can yield implantable grafts that combine synthetic grafts with living cells. Embodiments of systems can include a pressure/flow loop subsystem having an external flow loop system coupled to a specimen holder, where the pressure/flow loop subsystem is capable of adjusting at least two dynamic conditions in the specimen holder or a diameter of a specimen in the specimen holder. Embodiments of methods can promote endothelialization of a hybrid hemodialysis access graft or a hybrid femoral artery bypass graft by placing the hybrid hemodialysis access graft or the hybrid femoral artery bypass graft in a system embodiment according to the invention under conditions effective to promote endothelial cells to form a confluent monolayer on the surface of the hybrid graft.

Abstract: It has been discovered that there are at least two significant antigens present on the cells of animal species such as pigs that elicit an immune or inflammatory response immediately upon implantation into humans or contact with human serum. The first is an ?-galactosyl (Gal) epitope, for example, Gal?(1?3)Gal?(1?4)GlcNac (linear B type 2) or Gal? (1?3)Gal?(1?4)Glc (linear B type 6). The second is an N-glycolylneuraminic acid (NeuGc) structure. By eliminating these epitopes, preferably by genetically engineering the animal so that the epitope is either not produced or is greatly reduced, or by chemical or enzymatic treatment of the animal's cells to remove the epitopes, it is possible to produce organs, tissues and cells suitable for xenotransplantation into humans. Cells can be rendered even more compatible by genetically engineering the animal to express a human complement regulatory protein (inhibitor), such as CD59, on its cells, or to express an excess of a pig complement regulatory protein.

Abstract: A process for cleaning donor soft tissue by removing contaminants by extraction using a fluid at supercritical temperature and pressures while preserving the integrity of the tissue.

Abstract: Hybrid synthetic grafts and embodiments of systems and methods for producing hybrid vascular grafts that can yield implantable grafts that combine synthetic grafts with living cells. Embodiments of systems can include a pressure/flow loop subsystem having an external flow loop system coupled to a specimen holder, where the pressure/flow loop subsystem is capable of adjusting at least two dynamic conditions in the specimen holder or a diameter of a specimen in the specimen holder. Embodiments of methods can promote endothelialization of a hybrid hemodialysis access graft or a hybrid femoral artery bypass graft by placing the hybrid hemodialysis access graft or the hybrid femoral artery bypass graft in a system embodiment according to the invention under conditions effective to promote stem cells to form a confluent monolayer on the hybrid graft.

Abstract: Use of a composition which contains at least one semifluorinated alkane compound and at least one liquid siloxane, wherein the composition is of a density in a range of 0.8 to 1.5 g/cm3, for preserving organs or limbs.

Abstract: An apparatus for vitrifying a biological specimen includes a cap member, a tubular plunger, and a specimen chamber. The cap member includes a stem portion integrally formed with a receiving portion. The receiving portion has a disc-like shape and includes an outer surface. The outer surface includes a first skirt member comprised of a heat-sealable material. The first skirt member is attached along a circumferential portion of the outer surface. The specimen chamber has an open first end portion, a closed second end portion, and a cavity extending between the first and second end portions. The cavity is defined by oppositely disposed inner and outer surfaces. The specimen chamber further includes a second skirt member comprised of heat-sealable material. The second skirt member is attached along a circumferential portion of the outer surface.

Abstract: There is provided a method of making a renal tubule. The method comprises seeding renal tubule cells onto a solid surface; culturing the renal tubule cells in a liquid growth medium to form a monolayer on the solid surface; and continuing culturing the renal tubule cells to form a tubule.

Abstract: A liquid plasma expander or resuscitation fluid composition for use in a subject in need thereof, comprising, consisting of; or consisting essentially of: (a) a keratin derivative (preferably alpha keratose, gamma keratose, or combinations thereof, and with basic alpha keratose preferred over acidic alpha keratose); and (b) an electrolyte solution, with the keratin derivative solubilized in the electrolyte solution to form a homogeneous liquid composition. Blood substitutes formed therefrom and methods of making and using the same are also described.

Abstract: This invention relates to processes of preparing heterogeneous graft material from animal tissue. Specifically, the invention relates to the preparation of animal tissue, in which the tissue is cleaned and chemically cross-linked using both vaporized and liquid cross-linking agents, resulting in improved physical properties such as thin tissue and lowered antigenicity, thereby increasing the ease of delivering the tissue during surgery and decreasing the risk of post-surgical complication, respectively.

Abstract: Living cellular material may be preserved by incubating the cellular material in a culture medium containing at least one sugar, particularly for at least three hours, and then subjecting the cellular material to a preservation protocol, such as freezing, vitrification, freeze-drying and desiccation.

Abstract: A composition for protecting and/or preserving cells, tissues or organs, includes at least one cyclodextrin, preferably closely combined with an antioxidant. A process for producing this composition and its uses are also disclosed.

Abstract: The present invention provides methods for regrowth of conifer embryogenic cells. The methods comprise the steps of (a) contacting cryopreserved conifer embryogenic cells with a liquid transition medium, and (b) culturing the contacted conifer embryogenic cells in a regrowth medium to generate regrowth of the conifer embryogenic cells. Generally, the cryopreserved conifer embryogenic cells are contacted with the liquid transition medium for less than about 24 hours, such as for about one hour.

Abstract: Three-dimensional physiological matrices, methods, apparatus and kits for the expedited design, testing and evaluation of oncological remedies are provided. Key aspects of the inventions include matrices, and especially gel matrices, comprising one or more physiological fibers, which are adapted and arranged to provide conditions which permit behaviors, such as the movement of cells away from the margins of samples of target tissue through the matrix, to be evaluated in a manner that produces data useful for evaluating the oncological status and characteristics of the cells. In a further key aspect, the invention permits the in vitro testing and analysis of one or more conventional, experimental or theoretical therapies with respect to specific target tissues or cells. Among such therapies are therapeutic compounds and combinations thereof, radiation therapies, combinations of therapeutic compounds and radiation and numerous other possible therapies.

Abstract: A storage solution to maintain and perfuse organs awaiting transplantation comprising (a) an isotonic balanced solution comprising a physiologically acceptable amount of potassium, mono acidic phosphate, biacidic phosphate, chloride, sodium and bicarbonate ions; (b) 50-250 mM glucose; (c) 0.2-20 mM of an alkanoyl L-carnitine or a physiologically acceptable salt thereof; (d) 1-100 mM of L-carnitine or a physiologically acceptable salt thereof; (e) water is described. The storage solution can also include other components such as anti-oxidants and/or chelating agents.

Abstract: A method of treating a biological tissue that enables dry storage of said tissue is disclosed. In one embodiment, the method comprises contacting the biological tissue with a non-aqueous treatment solution comprising a polyhydric alcohol and a C1-C3 alcohol and removing a portion of the treatment solution from the solution-treated biological tissue. Also disclosed is biological tissue prepared using the above process and prosthetic devices made with such tissue.

Abstract: Solutions and suspensions comprising polymerized hemoglobin derived from human blood are disclosed. The solutions and suspensions may comprise cell culture medium, an enzyme (such as a protease), and/or a buffer. Processes of preparing the solutions and suspensions are also disclosed. The solutions and suspensions may be employed in methods of isolating mammalian cells, such as pancreatic islets, methods of preserving mammalian tissue and organs, methods of aiding the recovery of mammalian cells following their isolation, methods of maintaining mammalian cells, methods of propagating mammalian cells, and methods of treating a mammal with diabetes.

Abstract: An organ perfusion apparatus and method monitor, sustain and/or restore viability of organs and preserve organs for storage and/or transport. Other apparatus include an organ transporter, an organ cassette and an organ diagnostic device. The apparatus and methods further include a tube frame removably connected to the cassette and configured to hold a plurality of tubes in a position to be connected to tubes in the portable housing.

Abstract: A container is provided for holding a chemical compound or mixture. Areas are provided on the surface of the container which allow for gaseous by-products from the chemical contained within the container to permeate from a chamber through the surface of the container. A septum is over-molded into the surface of the container. The septum is formed in such a manner that it provides a sealing effect to close an opening in the container.

Abstract: The present invention concerns the use of oxygen antagonists for inducing stasis in tissue, including all or part of organs. It includes methods and apparatuses for achieving stasis in tissue, so as to preserve and/or protect them. In specific embodiments, preservation methods and apparatuses for preserving tissue for transplantation purposes is provided.

Abstract: The leading cause of graft failure is the subsequent development of intimal hyperplasia, which represents a response to injury that is thought to involve smooth muscle proliferation, migration, phenotypic modulation, and extracellular matrix (ECM) deposition. Surgical techniques typically employed for vein harvest—stretching the vein, placing the vein in low pH, solutions, and the use of toxic surgical skin markers—are shown here to cause injury. The invention therefore provides for non-toxic surgical markers than also protect against stretch-induced loss of functional viability, along with other additives. Devices and compositions for reducing physical stress or protecting from the effects flowing therefrom, also are provided.

Abstract: The present invention relates to a pharmaceutical composition comprising specific compounds which may be obtained from Leontopodium alpinum Cass. (Edelweiss). A preferred compound is leoligin (=(2S,3R,4R)-4-(3,4-dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)tetrahydrofuran-3-yl]methyl(2Z)-2-methylbut-2-enoat]). Corresponding means and methods in respect of medical uses of the compounds are described. The present invention also provides a medical device comprising, containing or having been contacted with the compound. The compounds provided herein may particularly be used in the treatment of hyperplastic diseases, in particular intimal hyperplasia, e.g. stenosis, restenosis, atherosclerosis and the like. Also envisaged herein is the use of these compounds in the treatment of proliferative diseases, such as leukemia, prostate cancer and lung cancer.

Abstract: A method for processing biological tissue used in biological prostheses includes providing a tissue procurement solution formed from a phosphate buffered saline (PBS) solution and a chelating agent. The tissue is transferred from the tissue procurement solution and undergoes chemical fixation. The fixed tissue is then immersed in a series of fresh bioburden reduction process (BRP) solutions to extract phospholipids. The tissue procurement solution reduces the bioburden on the stored tissue and preserves tissue architecture by minimizing tissue swelling. The tissue procurement solution further reduces calcium from the incoming water and/or tissue, and inhibits enzymes that digest the collagen matrix. The serial immersion of the tissue in the fresh bioburden solutions ensures optimal extraction of phospholipids thereby mitigating subsequent calcification of the tissue.

Abstract: A storage solution to maintain and perfuse organs awaiting transplantation comprising (a) an isotonic balanced solution comprising a physiologically acceptable amount of potassium, mono acidic phosphate, biacidic phosphate, chloride, sodium and bicarbonate ions; (b) 50-250 mM glucose; (c) 0.2-20 mM of an alkanoyl L-carnitine or a physiologically acceptable salt thereof; (d) 1-100 mM of L-carnitine or a physiologically acceptable salt thereof; (e) water is described. The storage solution can also include other components such as anti-oxidants and/or chelating agents.

Abstract: The present invention relates to S-allylmercapto-N-acetylcysteine (ASSNAC) and its pharmaceutically acceptable salts and solvates, which are useful for up-regulation of cellular glutathione levels and expression of phase II detoxifying enzymes. The invention further provides methods of use thereof in the prevention, alleviation or treatment of oxidative stress induced by reactive oxygen species (ROS).

Abstract: The present invention provides for compositions and methods for the preservation of tissues and organs ex vivo and in situ. In addition, the present invention provides for kits that may be used in the preparation of the solutions of the present invention.

Abstract: A medium solution which will increase the growth, survival and ultimately the live birth rate of oocytes and embryos which have been or will be subjected to cryopreservation. The solution contains varied amounts of glucose, pyruvates, amino acids, vitamins K5 and C, antioxidants, fatty acids to supply the specimens with the chemical ingredients and uptake requirements required to recover and prosper during and after the cryopreservation process. The solution supplies nutrients to the specimens that will replenish depletion and damage to the specimens and their mitochondria, spindles and structural features, such as cell walls. One formulation addresses the additional requirements of frozen specimens as opposed to the current media solutions and methods which treat the un-frozen specimens the same as the frozen specimens when recovering them from cryopreservation.

Abstract: A medium solution which will increase the growth, survival and ultimately the live birth rate of oocytes and embryos which have been or will be subjected to cryopreservation. The solution contains varied amounts of glucose, pyruvates, amino acids, vitamins K5 and C, antioxidants, fatty acids to supply the specimens with the chemical ingredients and uptake requirements required to recover and prosper during and after the cryopreservation process. The solution supplies nutrients to the specimens that will replenish depletion and damage to the specimens and their mitochondria, spindles and structural features, such as cell walls. One formulation addresses the additional requirements of frozen specimens as opposed to the current media solutions and methods which treat the un-frozen specimens the same as the frozen specimens when recovering them from cryopreservation.

Abstract: Three-dimensional physiological matrices, methods, apparatus and kits for the expedited design, testing and evaluation of oncological remedies are provided. Key aspects of the inventions include matrices, and especially gel matrices, comprising one or more physiological fibers, which are adapted and arranged to provide conditions which permit behaviors, such as the movement of cells away from the margins of samples of target tissue through the matrix, to be evaluated in a manner that produces data useful for evaluating the oncological status and characteristics of the cells. In a further key aspect, the invention permits the in vitro testing and analyses of one or more conventional, experimental or theoretical therapies with respect to specific target tissues or cells. Among such therapies are therapeutic compounds and combinations thereof, radiation therapies, combinations of therapeutic compound and radiation and numerous other possible therapies.

Abstract: The present invention relates to a new isolated cornea wherein the Descemet's membrane is separated from the overlying corneal stroma by an air cushion. For “DMEK” surgery a spatula (1) is provided, comprising a rounded glide (2) suitable for receiving on its upper surface (3) two overlapping separated buttons; said overlapping separated buttons comprising a lower button of support and an upper donor button to be introduced into the recipient's eye, a retaining means (4) of said overlapping separated buttons perimetrically disposed on a border (5) of said rounded glide (2) said retaining means (4) defining an aperture (6) suitable for extracting said upper button form said rounded glide (2) and a handle (7) solidly connected to said glide (2) and comprising a first portion (8) and a second portion (9), said first (8) and second (9) portions forming an a angle (10) with respect to each other.

Abstract: The present invention relates to a method for preserving biological material comprising the steps of: providing a vitrification solution comprised of the biological material and a vitrification agent where the solution has a temperature in the range from 0.1° C. to 17.9° C.; microwaving the vitrification solution for a first period of time; allowing the vitrification solution to rest for a second period of time; repeating steps b and c until the vitrification solution enters into a glassy state.

Abstract: The purpose is to proliferate a mesenchymal stem cell to a sufficient degree while reducing the amount of blood serum contained in a biological tissue progenitor cell to be grafted, and to efficiently differentiate the mesenchymal stem cell into the biological tissue progenitor cell. There is provided a method for culturing a mesenchymal stem cell, comprising: a first culture step of proliferating a mesenchymal stem cell in a medium containing blood serum; and a second culture step of differentiating the mesenchymal stem cell into a biological tissue progenitor cell in a medium containing blood serum at a lower concentration than that in the medium used in the first culture step.

Abstract: A treatment for bioprosthetic tissue used in implants or for assembled bioprosthetic heart valves to reduce in vivo calcification. The method includes applying a calcification mitigant such as a capping agent or an antioxidant to the tissue to specifically inhibit oxidation in tissue. Also, the method can be used to inhibit oxidation in dehydrated tissue. The capping agent suppresses the formation of binding sites in the tissue that are exposed or generated by the oxidation and otherwise would, upon implant, attract calcium, phosphate, immunogenic factors, or other precursors to calcification. In one method, tissue leaflets in assembled bioprosthetic heart valves are pretreated with an aldehyde capping agent prior to dehydration and sterilization.

Abstract: A method of yielding a functional human hybrid coronary bypass graft is provided. The method includes conditioning a hybrid synthetic tubular structure having stem cells and/or endothelial cells on at least one surface to yield the functional human hybrid coronary bypass graft. Specifically, the method includes placing the hybrid synthetic tubular structure in a system capable of producing three dimensional dynamic conditions for a sufficient time to yield said functional human hybrid coronary bypass graft.

Abstract: A method of yielding a functional human hybrid hemodialysis access graft is provided. The method includes conditioning a hybrid synthetic tubular structure having stem cells and/or endothelial cells on at least one surface to yield the functional human hybrid hemodialysis access graft. Specifically, the method includes placing the hybrid synthetic tubular structure in a system capable of producing three dimensional dynamic conditions for a sufficient time to yield said functional human hybrid hemodialysis access graft.