Abstract: A skin substitute membrane includes a surface on one side including a groove-shaped depressed portion and a planar portion, the depressed portion having a cross section having a chamfered V-letter shape, the surface having an arithmetic mean roughness Sa of more than or equal to 10 ?m to less than or equal to 50 ?m. The depressed portion has a width of more than or equal to 50 ?m to less than or equal to 500 ?m and a depth of more than or equal to 30 ?m to less than or equal to 150 ?m. A spectral transmittance for light of more than or equal to 290 nm to less than or equal to 400 nm in wavelength is more than or equal to 50% and less than or equal to 100%.

Abstract: The present specification generally relates to multifunctional polyethylene glycol-based crosslinking agents, hydrogel compositions comprising a matrix polymer crosslinked with such crosslinking agents, and methods of treating a soft tissue condition using such hydrogel compositions.

Abstract: An extracellular matrix (ECM)-based scaffold suitable for artificial skin as well as other structures can be formed using a bioreactor fabricated with a pattern that introduces desired structural features, on the microscale and/or nanoscale, to ECM-precursors gelled in the bioreactor. The bioreactor can produce a finely patterned scaffold—over clinically relevant size scales—sufficiently robust for routine handling. Preformed ECM-based scaffolds can also have microscale and/or nano-scale structural features introduced into a surface thereof. ECM-based scaffolds may be formed with well-defined structural features via microetching and/or remodeling via ‘contact degradation.’ A surface-activated pattern can be used to degrade the ECM-based scaffold at contact regions between the pattern and the ECM. The produced ECM-based scaffolds can have structures of dimensions conducive to host tissue ingrowth while preserving the fibrous structure and ligand density of natural ECMs.

Abstract: A fiber matrix is provided for maintaining space in soft tissue, for example for use in procedures for assisting drainage of aqueous humor from an eye to treat glaucoma. The fiber matrix comprises a plurality of crossing fibers forming a mesh with a plurality of void spaces. The fibers and void spaces are sized and arranged so as to permit passage of fluid through the fiber matrix and to inhibit formation of scar tissue through the fiber matrix. The fibers may comprise a polymeric material, and the fiber matrix may be manufactured by electrospinning. The fibers may comprise a biostable and/or a biodegradable material. In one method of using a fiber matrix, the fiber matrix is positioned under a scleral flap, with at least part of the fiber matrix under the scleral flap.

Abstract: An improved skin substitute is presented comprised of non-biological materials produced with a series of regularly-spaced pores and a nylon weave netting. The top component is a thin (approximately 0.001? thick) silicone elastomer in which pore holes have been vacuum-pulled; physically attached to the silicone elastomer is a fine knitted nylon fabric (12/1, 15/1 denier); incorporated into the silicone/nylon structure are collagen peptides [about 10 micrograms per square centimeter of Porcine type 1—“the active component”] without cross-linking agent to enable a quick interaction with fibrin in the wound to achieve acute adherence. The vacuum-pulled holes provide a range of porosities to ensure minimum fluid accumulation beneath the skin substitute without wound desiccation. The range of hole diameters preferred in the present invention is 0.75 mm to 1.05 mm and at holes centered at ¼?-??.

Abstract: The invention features methods of inducing hair follicle formation in a mammal by transplantation of skin-derived precursors (SKPs) and keratinocytes into the skin of the mammal. The invention also features compositions and kits including SKPs and keratinocytes. In other aspects, the invention features methods for producing dermal sheets from SKPs, methods for using such sheets and dermal sheets produced by SKPs.

Abstract: The present invention relates to a method of preparing a tissue graft material. The invention also relates to a multipurpose tissue graft material and to methods of using same as a replacement for vascular and non-vascular tissue.

Abstract: The present invention relates to a method for constructing human skin tissue, in which human skin tissue is reconstructed on a body surface of an immunodeficient non-human animal.

Abstract: An apparatus includes a fluid permeable dressing and a cover membrane configured to extend over the fluid permeable dressing. A tube is coupled to the fluid permeable dressing and is configured to apply suction through the fluid permeable dressing. A fluid reservoir is coupled to the cover membrane, the fluid vessel including an inlet port configured to receive a fluid and an outlet port fluidically coupled to the fluid permeable dressing.

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: Angiogenically induced transplants and methods for their use and manufacture are disclosed. The angiogenic potential of the transplants is increased by contacting the transplants with donor mesenchymal cells such as hair follicle dermal papilla stem cells. Methods for treating disorders and diseases, such as disorders of the skin and angiopathies, are also disclosed.

Abstract: The present invention provides devices and compositions for the management of infection of topical lesions, each of the devices and compositions containing protonated/acidified nucleic acids either on its surface, or integrated into the device. These modified nucleic acids are effective as bactericidal and/or bacteriostatic agents without regard to the class of bacteria, so are especially useful when diagnosis is difficult or when multiple infectious organisms are present. The antibiotic activity of nucleic acids of the invention is not dependent on either the specific sequence of the nucleic acid or the length of the nucleic acid molecule. The nucleic acids used in the invention are protonated/acidified to give a pH when dissolved in water of less than pH 7 to about 1, more preferably less than pH 4.5 to about 1, and even more preferably less than pH 2 to about 1.

Abstract: Wound closure systems and methods are provided, containing a porous layer comprising a collagen material; a substantially non-porous synthetic layer contacting the porous layer, the porous layer and substantially non-porous layer capable of providing wound closure; and a transcutaneous component contacting the porous layer and the substantially non-porous synthetic layer. In various embodiments, the transcutaneous component is capable of receiving a cannula, glucose sensor, electrode, prosthesis, chest tube, medical instrument or bone, muscle, blood vessels, nerve, organ or combination thereof.

Abstract: Artificial dermis (1) obtained from plasma with platelets (2) and human fibroblasts. The plasma with platelets (2) is obtained from the fractionating of total blood (4) from the patient (8) by light centrifugation, and the human fibroblasts (3) from a skin biopsy (5). Clotting is obtained by adding calcium. This artificial dermis (1) provides for the rapid growth of the keratinocytes (6) seeded on its surface to build an artificial skin (7) which can easily be transplanted. Large areas of artificial dermis (1) are obtained from a small skin biopsy (5) and minimal quantities of plasma with platelets (2), which being enriched with cytokines and platelet growth factors, strengthens the proliferation of the cells seeded, both inside and on the surface. The artificial skin (7) obtained can be used to treat major burn treatments, chronic skin ulcers, etc., or be used, by employing genetically altered cells, as a vehicle for gene therapy.

Abstract: A method of securing a soft tissue implant to damaged tissue of a patient is provided. The method includes preparing a layer of extracellular matrices (ECM) for surgery. The method further includes stretching the layer on a frame and securing the layer to the frame. The method includes placing a top surface of the layer adjacent the damaged tissue, drilling multiple holes generally simultaneously through the layer and tissue, and simultaneously inserting a fastener into each drilled hole.

Abstract: Artificial skin having a thickness of 100 to 1,000 ?m, and prepared from a polymer which, when formed into a thin film having a thickness of 100–1,000 ?m, exhibits a percent transmission of light having a wavelength of 450–280 nm of at least 10%. In the artificial skin of the present invention, grooves which imitate furrows are provided on one surface. Also disclosed is a method for evaluating UV screening agents making use of the artificial skin of the present invention, on the basis of the relation between UV shielding power of a UV screening agent and UV transmission through the artificial skin.

Abstract: The present invention relates to in vitro cultured skin substitutes, and in particular to in vitro cultured skin substitutes that have improved barrier function. In some embodiments, improved barrier function is a result of improved culture conditions, while in other embodiments, improved barrier function results from genetic modification of keratinocytes. Improved culture conditions to improve barrier function include organotypic culture in the presence of linoleic acid and/or linoleic acid at about 75% humidity. Suitable genetic modifications for improving barrier function includes transfection with a DNA construct capable of expressing GKLF.

Abstract: A chimeric skin comprising immortalized human keratinocyte cells cocultured with donor keratinocytes is disclosed.

Abstract: An apparatus and method of using the apparatus to prepare a biocompatible biodegradable matrix capable of supporting cells to form an implantable or engraftable surgical device. A matrix-forming fluid is contained within a chamber defined by top and bottom surfaces of a thermally conductive material and spacers defining the thickness of the matrix. The chamber is then cooled to freeze the solution at a controlled rate, resulting in a matrix with a desired and uniform thickness having symmetric and uniform reticulations. The apparatus and method reproducibly forms such a matrix, which may be populated with cells for transplantation and engraftment into a wound.

Abstract: The invention relates to methods of stabilizing glycosaminoglycans in a biological tissue (e.g. a bioprosthetic implant) in conjunction with cross-linking of protein in the tissue. The methods of the invention improve the mechanical integrity of the device and improves its stability in vivo. The invention also includes biological tissues having stabilized glycosaminoglycans and cross-linked proteins and kits for preparing such tissues.

Abstract: A braided suture for skin lifting comprising gold threads and bioabsorbable threads, wherein the gold threads and bioabsorbable threads are braided to form a braided composite suture. A method of skin lifting providing a braided composite suture comprising gold threads and bioabsorbable threads and implanting the braided composite suture intradermally at a plurality of skin regions.

Abstract: A spontaneously immortalized human keratinocyte cell line is disclosed. In a preferred embodiment, this cell line is ATCC 12191. In another embodiment of the invention, a method of assaying the effect of a test tumor cell modulation agent is disclosed. The method comprises the steps of obtaining a human stratified squamous epithelial cell culture, wherein the culture comprises human malignant squamous epithelial cells and spontaneously immortalized human keratinocytes, wherein the culture forms a reconstituted epidermis. One then treats the epidermis with a test tumor cell modulation agent and evaluates the growth of the malignant cells within the epidermis.

Abstract: A composite product is disclosed as a collagen support comprising at least one porous collagen layer covered on at least one side with an essentially compact collagen membrane consisting either of a collagen film prepared by drying a collagen gel, preferably in air or a gaseous fluid, or of a very highly compressed collagen sponge. At least one of the two layers, i.e. the porous layer and the essentially compact membrane, may comprise normal, genetically modified or malignant living cells originating particularly from young or elderly subjects. This composite product is used as a collagen support for the manufacture of artificial skin intended especially for performing in vitro tests on the efficacy of potentially active substances or for reconstructing damaged areas of skin in vivo.

Abstract: Autologous cultured keratinocytes are grown on a biosynthetic and biocompatible substratum following pre-seeding with autologous or allogenic dermal fibroblasts. The resultant composite material may then be applied on the neodermis of artificial skin which had been previously engrafted on the patient. The composite material, and specifically Composite Biocompatible Skin Graft (CBSG) material comprises autologous keratinocytes and allogenic or autologous dermal fibroblasts grown on Laserskin. A method for cultivating the CBSG includes the application of dermal fibroblasts onto the substratum as a feeder layer and then the inoculation of autologous keratinocytes on the resultant structure. A method for engraftment comprises first applying an artificial skin with a protective silicone membrane on a wound area, thereby allowing vascularization; and following vascularization, removing the silicone membrane and engrafting the CBSG material onto the vascularized artificial skin.

Abstract: Autologous cultured keratinocytes are grown on a biosynthetic and biocompatible substratum following pre-seeding with autologous or allogenic dermal fibroblasts. The resultant composite material may then be applied on the neodermis of artificial skin which had been previously engrafted on the patient. The composite material, and specifically Composite Biocompatible Skin Graft (CBSG) material comprises autologous keratinocytes A and allogenic or autologous dermal fibroblasts grown on an artificial skin. A method for cultivating the CBSG includes the application of dermal fibroblasts onto the substratum as a feeder layer and then the inoculation of autologous keratinocytes on the resultant structure. A method for engraftment comprises first applying an artificial skin with a protective silicone membrane on a wound area, thereby allowing vascularization; and following vascularization, removing the silicone membrane and engrafting the CBSG material onto the vascularized artificial skin.

Abstract: The present invention is a synthetic, biocompatible, bioabsorbable, porous foam tissue scaffolds possessing physicochemical properties suitable for use in the repair and regeneration of dermal tissue and to methods of preparing the foam scaffold.

Abstract: Disclosed are a dermal scaffold comprising alkaline pre-treated free amine-containing chitosan matrix, alkaline pre-treated free amine-containing chitosan and alkaline pre-treated collagen mixed matrix, or alkaline pre-treated free amine-containing chitosan and alkaline pre-treated collagen mixed matrix containing chitosan fabrics, which has excellent wound healing effect by constituting microenvironments suitable for migration and proliferation of fibroblasts and vascular cells surrounding the wound to be extremely useful as wound healing dressings, and a bioartificial dermis comprising the dermal scaffold and human fibroblasts, particularly useful for healing broad wound sites such as burns.

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: An implant for tissue repair includes a support member, a flexible member coupled to the support member, and a substrate coupled to the support member. The substrate includes a material capable of being seeded with and supporting the proliferation of cells. The support member is capable of distributing a load throughout the flexible member. The flexible member includes parallel elongate elements and the support member serves to maintain a spacing between the parallel elongate elements.

Abstract: A spontaneously immortalized human keratinocyte cell line is disclosed. In a preferred embodiment, this cell line is ATCC 12191. In another embodiment of the invention, a method of assaying the effect of a test tumor cell modulation agent is disclosed. The method comprises the steps of obtaining a human stratified squamous epithelial cell culture, wherein the culture comprises human malignant squamous epithelial cells and spontaneously immortalized human keratinocytes, wherein the culture forms a reconstituted epidermis. One then treats the epidermis with a test tumor cell modulation agent and evaluates the growth of the malignant cells within the epidermis.

Abstract: An in vitro, three dimensional artificial tissue that resembles human skin has been developed. Microvascular endothelial cells from human adult lung were sandwiched between two layers of human dermal fibroblasts in three dimensional collagen gels. The sandwich was covered with keratinocytes. The cultures were self-maintained for prolonged periods of time without the addition of tumor promoters such as phorbol esters. Over a few days, the keratinocytes developed into a multilayered epithelium. Microvessels were produced in the support matrix. The microvessels were composed of a tight monolayer of endothelial cells surrounded by a continuous basal lamina, contacted by newly formed, sparse perioendothelial cells. The microvessels also contained newly formed blood cells. Human matrix molecules characteristic of skin were produced.

Abstract: Artificial skin having a thickness of 100 to 1,000 &mgr;m, and prepared from a polymer which, when formed into a thin film having a thickness of 100-1,000 &mgr;m, exhibits a percent transmission of light having a wavelength of 450-280 nm of at least 10%. In the artificial skin of the present invention, grooves which imitate furrows are provided on one surface. Also disclosed is a method for evaluating UV screening agents making use of the artificial skin of the present invention, on the basis of the relation between UV shielding power of a UV screening agent and UV transmission through the artificial skin.

Abstract: The present invention provides synthetic, biocompatible, bioabsorbable, porous foam tissue scaffolds possessing physicochemical properties suitable for use in the repair and regeneration of dermal tissue and to methods of preparing such foam scaffolds.

Abstract: Use of collagen of aquatic origin for the production of supports for tissue engineering is disclosed. The collagen may be obtained from fish skin, preferably in its native form. Novel tissue engineering supports with a low risk of contamination are produced.

Abstract: A biomaterial is provided which is suitable for use in surgery in a human patient. It includes a coherent layer of non-human collagenous tissue which has been subjected to glutaraldehyde tanning so as to include cross-linked collagen fibrils, and a reinforcement of synthetic material embedded within the coherent layer. The synthetic material has structure features for promoting the embedding, the synthetic material having on average in situ more than 50 of the features per square centimeter.

Abstract: Novel osteopontin derived chemotactic peptides are described. The peptides (or antagonists thereof) are useful in treating conditions or diseases associated with chemotaxis.

Abstract: A spontaneously immortalized human keratinocyte cell line is disclosed. In a preferred embodiment, this cell line is ATCC 12191. In another embodiment of the invention, a method of assaying the effect of a test tumor cell modulation agent is disclosed. The method comprises the steps of obtaining a human stratified squamous epithelial cell culture, wherein the culture comprises human malignant squamous epithelial cells and spontaneously immortalized human keratinocytes, wherein the culture forms a reconstituted epidermis. One then treats the epidermis with a test tumor cell modulation agent and evaluates the growth of the malignant cells within the epidermis.

Abstract: A spontaneously immortalized human kerazinocyte cell line is disclosed. In a preferred embodiment, this cell line is ATCC 12191. In another embodiment of the invention, a method of assaying the effect of a test tumor cell modulation agent is disclosed. The method comprises the steps of obtaining a human stratified squamous epithelial cell culture, wherein the culture comprises human malignant squamous epithelial cells and spontaneously immortalized human keratinocytes, wherein the culture forms a reconstituted epidermis. One then treats the epidermis with a test tumor cell modulation agent and evaluates the growth of the malignant cells within the epidermis.

Abstract: The present invention provides a number of novel implants for use in cosmetic and reconstructive nasal surgery, and kits and structural elements comprising various combinations of those implants. The invention includes a technique for securing various implants to each other that will reduce the complexity of the surgery and the required operating time. Another aspect of the invention includes structures that permit the quick and yet secure attachment to each other of various elements, in a way that the surgeon can use to build up a desired shape and provide actual structural support for the involved portion of the patient's features.

Abstract: Disclosed are a dermal scaffold comprising alkaline pre-treated free amine-containing chitosan matrix, alkaline pre-treated free amine-containing chitosan and alkaline pre-treated collagen mixed matrix, or alkaline pre-treated free amine-containing chitosan and alkaline pre-treated collagen mixed matrix containing chitosan fabrics, which has excellent wound healing effect by constituting microenvironments suitable for migration and proliferation of fibroblasts and vascular cells surrounding the wound to be extremely useful as wound healing dressings, and a bioartificial dermis comprising the dermal scaffold and human fibroblasts, particularly useful for healing broad wound sites such as burns.

Abstract: The invention relates to an artificial skin based on a copolymer of a polyalkylene glycol and an aromatic polyester, which skin has a thickness between 50 and 2000 &mgr;m, and which skin has an upper and a lower side, both having a macroporosity between 10% and 95%.

Abstract: The invention relates to an artificial skin based on a copolymer of a polyalkylene glycol and an aromatic polyester, which skin has a thickness between 50 and 2000 &mgr;m, and which skin has an upper and a lower side, both having a macroporosity between 10% and 95%.

Abstract: Artificial skin having a thickness of 100 to 1,000 &mgr;m, and prepared from a polymer which, when formed into a thin film having a thickness of 100-1,000 &mgr;m, exhibits a percent transmission of light having a wavelength of 450-280 nm of at least 10%. In the artificial skin of the present invention, grooves which imitate furrows are provided on one surface. Also disclosed is a method for evaluating UV screening agents making use of the artificial skin of the present invention, on the basis of the relation between UV shielding power of a UV screening agent and UV transmission through the artificial skin.

Abstract: A method for spreading skin grafts, wherein the skin grafts are placed on an elastic membrane, after which the membrane is stretched in at least two directions substantially perpendicular to each other and the skin grafts present on the membrane are spread. A spreading means, a stretcher and a membrane to be used therewith, as well as to a method for applying skin grafts to a burn.

Abstract: The invention provides a biocompatible composite for use in a living subject for purposes of repairing damaged tissues and reconstructing a new tissue. The composite includes a biodegradable or absorbable three-dimensional support construct, a liquid or viscous fluid forming a gel matrix or viscous fluid when delivered to an area of interest in a living subject. The biodegradable construct provides an ideal surface for cell or cell extract attachment, while the gel matrix or viscous fluid acts as both a carrier material and a separator for maintaining the space between the constructs as well as the structural integrity of the developing issue.

Abstract: An implantable tissue augmentation device having a multiplicity of biocompatible strands, each of said strands having at least one end wherein the multiplicity of strands are integrally joined at the at least one end of each of the multiplicity of strands. Optionally, the augmentation device has an attachment feature allowing easy attachment to a suture, a needle or other surgical instrument. The strands can have various cross sectional configurations such as rectangles or polygons.

Abstract: A system for molding a tissue or substitute tissue product in a mold having an exterior surface, and an interior surface, wherein at least one portion of the interior surface is porous and whose pores are in continuous communication with the exterior surface, and wherein said mold can be fabricated using solid free-form fabrication techniques is disclosed.