Abstract: Endothelialization of vascular surfaces. According to one aspect, the invention involves a technique for re-endothelializing an artery whose endothelial layer has been damaged by balloon angioplasty. The technique comprises, in one embodiment, introducing into the bloodstream of a patient, prior to performing the angioplasty, a quantity of a bispecific antibody, the bispecific antibody having a first antigen binding site directed against a surface marker common to both endothelial progenitor cells (EPCs) and endothelial cells (ECs) and having a second antigen binding site directed against a subendothelial epitope. The bispecific antibody is introduced in a quantity sufficient to bind a substantial percentage of circulating EPCs and circulating ECs. In this manner, once the angioplasty has been performed and the target epitopes on the subendothelium have been exposed, the bispecific antibodies that have already become bound to the circulating EPCs and ECs also then bind to the subendothelium.

Abstract: The invention relates to the use of a recipient-specific transformed synthetic or natural acellularized matrix for the production of an individual venous valve prosthesis.

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: An intestinal submucosa tissue graft construct for use in repairing diseased or damaged tissues is provided. The graft construct comprises vertebrate intestinal submucosa tissue, added endothelial cells, and at least one additional preselected, exogenous population of cells which enhances initiation of the formation of vessel-like structures in the graft. 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 intestinal submucosa tissue graft constructs and for preparing these graft constructs are also provided.

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 liver basement membrane and extracts and hydrolysates thereof, and processed collagen from vertebrate non-submucosal sources, added endothelial cells, and at least one additional preselected, exogenous population of cells which enhance the initiation of vessel-like structures in the grant. 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.

Abstract: This invention is directed to a tissue-engineered stent comprising a substantially cylindrical construct (10) having a first end (12) and a second end (14); a walled surface (16) disposed between the first end and the second end; the walled surface (16) comprising a biodegradable polymer scaffold seeded with disassociated chondrocytes. In one embodiment, the seeded scaffold is cultured in vitro prior to implantation in a host for a time period sufficient for cartilaginous tissue to form.

Abstract: The invention is directed to bioengineered vascular graft support 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: A method of using body tissue includes obtaining graft tissue. A medicinal substance is added to the graft tissue. The graft tissue is shaped to a predetermined configuration while the graft tissue is outside of a patient's body. The graft tissue is moved into the patient's body while the graft tissue has the predetermined configuration. While the graft tissue is in the patient's body, the graft tissue is allowed to expand and absorb liquid from the patient's body. A mechanical interlock may be established between the graft tissue and tissue in the patient's body during expansion of the graft tissue and absorption of liquid from the patient's body.

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 present invention generally relates to methods and apparatus for use in endovascular and intraoperative procedures providing arterial blood flow for perfusion of ischemic myocardium. Aspects of the present invention provide a conduit between a non-coronary sinus of the aorta and a coronary vein. The conduit traverses a portion of the right atrium and the coronary sinus, and is located entirely within the heart and aorta. Arterial blood flows from the aorta through the conduit and into the coronary venous circulation towards the ischemic region of the heart. All procedures described herein may be performed endovascularly, and further may be performed while the patient's heart is beating.

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: The invention is directed to bioengineered 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 use in a mammalian host.

Abstract: A tube system (1) for reconstructing a hollow organ, comprising a tube (2) for draining a substance, like e.g. urine, wherein the tube (2) for draining the substance is arranged within an outer tube (5) and that the space (4) between the two tubes (2, 5) is provided for the application of cells, and wherein the outer tube (5) is formed by a membrane (5) permeable for the cells to be applied, in particular a micro-perforated membrane (5).

Abstract: A method for implanting cells onto a prosthesis includes the steps of: (a) providing a prosthesis including a porous tube, where at least 25% of the pores on the inner surface of the tube have diameters of more than about 40 &mgr;m, at least 25% of the pores on the outer surface of the tube have diameters of less than about 30 &mgr;m, and the tube includes a substantially continuous layer of a biocompatible material; (b) contacting the prosthesis with a suspension of cells; and (c) providing a pressure differential between the inner surface and the outer surface, whereby the cells are retained in the pores of the inner surface. A method for obtaining an endothelial cell culture from a blood sample involved:(a) obtaining a sample for mononuclear cells from a blood sample; and (b) culturing the sample of mononuclear cells, without further cell separation, on a cell adhesive polymer-coated solid support in the presence of endothelial growth factors.

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: The present invention provides a microfistula tube including a soluble duct, defining a drainage canal having an inner surface, the duct being biocompatible, wherein the microfistula tube is coated with and/or incorporates biological for forming a basement membrane, or an intracellular matrix and a basement membrane. The biological cells may coat the inner surface of the drainage canal, and the microfistula tube may be made of a mouldable material or an absorbable material. The invention also provides an implantation system for the microfistula tube including a microfistula tube and a surgical instrument including an outer tube for penetrating body tissue, an inner tube, and an innermost rod, wherein the outer tube, the inner tube and the innermost rod are coaxial, the outer tube is adapted to receive said microfistula tube, whereby the inner tube may be used to push the microfistula tube into position and the innermost rod provides mechanical support during implantation of the microfistula tube.

Abstract: A device and a method of maintaining vascularization near an implant, especially a bioartificial hemofilter. By associating cells that excrete angiogenic factors with such an implant, vascularization to the tissue surrounding the implant can be maintained. In a bioartificial hemofilter, this facilitates filtrate transport to a collection fiber for drainage from the body. The cells can be genetically engineered, for example using an adenovirus vector encoding for vascular endothelial growth factor. Myoblasts and myotubes may be used in one embodiment of the present invention.

Abstract: The invention is a tissue engineered blood vessel (TEBV) made from a cultured fibroblast sheet rolled into a multilayer vessel which has sufficient burst strength to withstand physiological blood pressure without the inclusion of smooth muscle cells or synthetic scaffolding. The TEBV is made in a bioreactor having an enclosed chamber, a sheet growth module, a rollable mandrel and a clamp for holding the sheet to the mandrel for rolling.

Abstract: The invention is a tissue engineered blood vessel (TEBV) made from a cultured fibroblast sheet rolled into a multilayer vessel which has sufficient burst strength to withstand physiological blood pressure without the inclusion of smooth muscle cells or synthetic scaffolding. The TEBV is made in a bioreactor having an enclosed chamber, a sheet growth module, a rollable mandrel, and a clamp for holding the sheet to the mandrel for rolling.

Abstract: A covered stent assembly comprising a tubular, expandable stent having a metallic framework covered with a cylinder of biocompatible, non-thrombogenic expandable material, such as heterologous tissue. In a preferred embodiment, the metallic framework is positioned coaxially within a cylinder of bovine pericardial tissue. A catheter may be used to deliver the stent assembly to a desired region in the lumen of a patient. The metallic framework is then expanded to seat the assembly within the lumen.

Abstract: A stent cover useful as a barrier between an expandable stent and the vascular surface. The cover provides an optimal combination of such properties as thickness, physical characteristics and biocompatability. The cover can be formed to and positioned upon the size and shape of the unexpanded stent, and to then be expanded in situ upon expansion of the stent itself. The cover is prepared from natural tissues such as umbilical arteries, bovine pericardium, and porcine peritoneum.

Abstract: A novel process for paving or sealing the interior surface of a tissue lumen by entering the interior of the tissue lumen and applying a polymer to the interior surface of the tissue lumen. This is accomplished using a catheter which delivers the polymer to the tissue lumen and causes it to conform to the interior surface of lumen. The polymer can be delivered to the lumen as a monomer or prepolymer solution, or as an at least partially preformed layer on an expansible member.

Abstract: The invention relates to the use of a natural tissue matrix which has undergone recipient-specific transformation for producing an individual vein valve prosthesis without the natural tissue matrix having been acellularized.

Abstract: The invention is directed to formation and use of electroprocessed collagen, including use as an extracellular matrix and, together with cells, its use in forming engineered tissue. The engineered tissue can include the synthetic manufacture of specific organs or tissues which may be implanted into a recipient. The electroprocessed collagen may also be combined with other molecules in order to deliver substances to the site of application or implantation of the electroprocessed collagen. The collagen or collagen/cell suspension is electrodeposited onto a substrate to form tissues and organs.

Abstract: The present invention is directed to various products and processes comprising segments of vasculature from long-necked birds for use as vascular grafts. Also contemplated is a process for preparing this vasculature for use as a small-bore vascular graft. The isolated vasculature of the present invention is of sufficient length to be used in a variety of applications, and may be stored for extended lengths of time after isolation or processing before implantation.

Abstract: Disclosed herein is a method for implanting cells onto a prosthesis, including the steps of: (a) providing a prosthesis including a porous tube, where at least 25% of the pores on the inner surface of the tube have diameters of more than about 40 &mgr;m, at least 25% of the pores on the outer surface of the tube have diameters of less than about 30 &mgr;m, and the tube includes a substantially continuous layer of a biocompatible material; (b) contacting the prosthesis with a suspension of cells; and (c) providing a pressure differential between the inner surface and the outer surface, whereby the cells are retained in the pores of the inner surface. Also disclosed herein are methods for culturing cells for implantation.

Abstract: An endovascular support device adapted for local delivery of a therapeutic agent and for minimizing the rate of restinosis having a cylindrical support body with an inside surface and an opposite outside surface, and at least one layer of pericardial tissue covering at least a portion of at least a selected one of the inside surface or the outside surface of the cylindrical support body. At least one therapeutic agent is disposed on a portion of the support device.

Abstract: Disclosed herein is a method for implanting cells onto a prosthesis, including the steps of: (a) providing a prosthesis including a porous tube, where at least 25% of the pores on the inner surface of the tube have diameters of more than about 40 &mgr;m, at least 25% of the pores on the outer surface of the tube have diameters of less than about 30 &mgr;m, and the tube includes a substantially continuous layer of a biocompatible material; (b) contacting the prosthesis with a suspension of cells; and (c) providing a pressure differential between the inner surface and the outer surface, whereby the cells are retained in the pores of the inner surface. Also disclosed herein are methods for culturing cells for implantation.

Abstract: An improved prosthetic graft for the bypass, replacement or repair of vessels and organs that are in contact with blood flow is disclosed. The prosthetic graft includes a porous prosthetic implant and adherent cells adhered to the outer surface of the implant. The adherent cells are transfected with at least one recombinant nucleic acid molecule encoding at least one protein that enhances patency of the graft. The prosthetic graft has a long-term patency and success rate that is superior to other previously described prosthetic grafts designed for such use. Also disclosed are methods of making and using such a graft.

Abstract: Disclosed is a smooth muscle cell specific promoter, the SM22&agr; gene promoter as well as the murine cDNA and genomic SM22&agr; nucleic acid sequences. Also disclosed are methods of preventing restenosis following balloon angioplasty and methods of treating asthma based on inhibition of smooth muscle cell proliferation by expressing cell cycle control genes, or contraction inhibiting peptides in smooth muscle cells, under the control of the SM22&agr; promoter.

Abstract: An improved prosthetic graft for the bypass, replacement or repair of vessels and organs that are in contact with blood flow is disclosed. The prosthetic graft includes a porous prosthetic implant and adherent cells adhered to the outer surface of the implant. The adherent cells are transfected with at least one recombinant nucleic acid molecule encoding at least one protein that enhances patency of the graft. The prosthetic graft has a long-term patency and success rate that is superior to other previously described prosthetic grafts designed for such use. Also disclosed are methods of making and using such a graft.

Abstract: The present invention relates to decellularized vascular prostheses that are resistant to thrombus occlusion and have a low level of immunogenicity. The vascular prostheses are denuded of cells, and coated with an anti-thrombogenic agent and a growth factor that promotes recellularization and further reduces the immunogenicity. The prostheses have high mechanical strength, resist aneurysm rupture, and allow for secure surgical sutures while maintaining structural integrity. The present invention provides vascular prostheses that are blood vessels, valves or portions of vessels containing valves. The present invention is also useful for coating synthetic vascular stents.

Abstract: An implantable system that includes a carrier and eukaryotic cells, which produce and release a therapeutic agent, and a stimulating element for stimulating the release of the therapeutic agent. The system can also include a sensing element for monitoring a physiological condition and triggering the stimulating element to stimulate the delivery device to release the therapeutic agent. Alternatively, the patient in which the system is implanted can activate the stimulating element to release the therapeutic agent.

Abstract: An implantable prosthesis includes a porous polymeric member having pores present in its wall structure wherein these pores contain a variety of therapeutically useful compositions including, collagen, genetically altered cells and piezoelectric materials. A process of preparing such a prosthesis is also disclosed.

Abstract: Solid free-form fabrication (SFF) methods are used to manufacture devices for allowing tissue regeneration and for seeding and implanting cells to form organ and structural components, which can additionally provide controlled release of bioactive agents, wherein the matrix is characterized by a network of lumens functionally equivalent to the naturally occurring vasculature of the tissue formed by the implanted cells, and which can be lined with endothelial cells and coupled to blood vessels at the time of implantation to form a vascular network throughout the matrix. The SFF methods can be adapted for use with a variety of polymeric, inorganic and composite materials to create structures with defined compositions, strengths, and densities, using computer aided design (CAD). Examples of SFF methods include stereo-lithography (SLA), selective laser sintering (SLS), ballistic particle manufacturing (BPM), fusion deposition modeling (FDM), and three dimensional printing (3DP).