Abstract: A single-layer tissue sheet having a puncture strength of 2 kgf to 6 kgf. A valve, such as a heart valve, made of one or more leaflets formed from a single-layer tissue sheet. A method of making a tissue sheet having a puncture strength of 2 kgf to 5 kgf. The ultra-strong tissue sheets described herein have very long culture times, such as in excess of 20 weeks. Valves that comprise one or more leaflets made from the ultra-strong tissue sheets described herein may be delivered via trans-cathete aortic valve implantation.

Abstract: The technology described herein generally relates to the field of tissue engineering and treatment of cardiovascular disease by endovascular repair. The technology more particularly relates to devices and methods to produce a tissue-based implant that can be used for abdominal aorta aneurysm, thoracic aorta aneurysm, or other cardiovascular repair.

Abstract: The disclosure provides methods and compositions to build living tissue covered stents and the like. These tissue coated stents provide a barrier against cell migration to the lumen of the vessel. Since the tissue can surround and envelope the stent, foreign body responses to the stent material are reduced and delayed. The tissue coating is also relatively impermeable to transmural flow, so the wrapped stent can act as a bypass vessel. The tissue is also robust enough to act as a stand alone vessel, without requiring the presence of the metallic stent. These stents can be endothelialized to reduce thrombosis. The genetic modifications described in this disclosure allow for functional organs to be built that express agents that are anti-restenotic or anti-thrombogenic.

Abstract: The invention relates to bioreactors having an enclosed chamber, a sheet growth module, a rollable mandrel, and a clamp for holding the sheet to the mandrel for rolling for the manufacture of a tissue engineered blood vessel (TEBV). The TEBV is 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.

Abstract: The disclosure provides methods and composition to build living tissue covered stents and the like. These tissue coated stents provide a barrier against cell migration to the lumen of the vessel. Since the tissue can surround and envelope the stent, foreign body responses to the stent material are reduced and delayed. The tissue coating is also relatively impermeable to transmural flow, so the wrapped stent can act as a bypass vessel. The tissue is also robust enough to act as a stand alone vessel, without requiring the presence of the metallic stent. These stents can be endothelialized to reduce thrombosis. The genetic modifications described in this disclosure allow for functional organs to be built that express agents that are anti-restenotic or anti-thrombogenic. The use of tissue manipulation devices further allows for the assembly of complex tissue engineered organs.

Abstract: The disclosure provides methods and systems for tissue engineering including an apparatus and methods for the growth, maintenance, and use of robust tissue sheets using tissue manipulation devices. The tissue manipulation devices provide a method of anchoring the tissue sheets to the cell culture substrate to promote prolonged maturation and subsequent increased mechanical strength. The tissue manipulation devices also provide a technique to facilitate removal of the sheet from the culture container and subsequent production steps to assemble more complex three dimensional organs from the robust sheet. The tissue manipulation devices also facilitate automated handling of the sheets in the assembly processes. The disclosure provides methods and composition derived from robust human sheets to build tissue engineered blood vessels, heart valves, stents, and endarterectomy patches and the like.

Abstract: The disclosure provides methods and systems for tissue engineering including an apparatus and methods for the growth, maintenance, and use of robust tissue sheets using tissue manipulation devices. The tissue manipulation devices provide a method of anchoring the tissue sheets to the cell culture substrate to promote prolonged maturation and subsequent increased mechanical strength. The tissue manipulation devices also provide a technique to facilitate removal of the sheet from the culture container and subsequent production steps to assemble more complex three dimensional organs from the robust sheet. The tissue manipulation devices also facilitate automated handling of the sheets in the assembly processes. The disclosure provides methods and composition derived from robust human sheets to build tissue engineered blood vessels, heart valves, stents, and endarterectomy patches and the like.

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: 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: Bone precursor compositions, methods of preparation and use are described. Bone precursor compositions include a calcium cement which is suitable for injection, wherein the calcium cement includes monobasic calcium phosphate monohydrate and beta-tricalcium phosphate. The bone precursor compositions can further include biopolymer foams, collagen, extracellular matrix components, therapeutic agents, or biopolymer fibers. The bone precursor compositions can also include or be conditioned with cells, such as connective tissue cells, preferably bone tissue cells.

Abstract: Single and double density biopolymer foams, composite biopolymer foams including both single and double density foams, and methods of preparing these foams and composite foams are described. Also described are biocompatible constructs which include single or double density biopolymer foams and extracellular matrix particulates and methods of preparing these constructs. The foams, composite foams, and biocompatible constructs of the invention can be used in tissue repair and reconstruction.

Abstract: Apparatus and methods are disclosed for maturing an elongate replacement tissue construct in vitro prior to use of the replacement construct in vivo as, for example, a ligament. The tissue is seeded with specific cells, exposed to a maturation fluid, and subjected to selected forces, which can include longitudinal stress, (i.e. stressing the tissue along its elongate axis). The tissue is disposed in a maturation chamber that confines maturation fluid for introduction to the tissue. A first mounting element couples to a first end of the elongate biopolymer tissue and a second mounting element couples to a second end of the tissue such that the tissue extends along a longitudinal axis, and a force is applied to at least one of the mounting elements for longitudinally stressing the tissue. The foregoing apparatus and methods are intended to provide a replacement tissue that is more readily integrable in vivo, i.e.

Abstract: Using animal tissues as starting materials, a method is described for producing extracellular matrix particulates. The invention includes an embodiment wherein the matrix particulates are applied to collagen scaffolds, which can be seeded with living cells or the particulates may alone be seeded with living cells. Further, the invention encompasses bonding the particulates to collagen foams, or collagen threads made into fabrics or to foams combined with threads. The particulates, with or without scaffolding, can be used as tissues for grafting or as model systems for research and testing. The invention also encompasses the spinning of threads on which the matrix particulates are components and the freeze drying of foams to whose surfaces the matrix particulates are attached.

Abstract: Method and apparatus are disclosed for removing biopolymer constructs from support structures used to impart a selected shape to the biopolymer. The biopolymer construct and the support structure are in intimate at an interface and adhere to each other. The support structure includes an endcap adapted for introducing a fluid to the interface for reducing adhesion between the biopolymer structure and the support structure by applying a separating force at the interface, thereby facilitating removal between the support structure and the biopolymer construct.

Abstract: A biopolymer solution is polymerized to form a gel which is freeze-dried and crosslinked with ultraviolet radiation to form a biopolymer foam. The foam is filled with a collagen solution and the combination is freeze-dried or the foam is filled with a collagen solution containing extracellular matrix particulates and that combination is freeze-dried, thereby forming a foam to which extracellular matrix particulates are attached.

Abstract: An apparatus for forming a collagen fiber having microparticulates coated on the surface of the fiber and the method for forming the fiber are disclosed.

Abstract: Using connective tissues as starting materials, a method is described for producing matrix particulates. The invention includes an embodiment wherein the matrix particulate are seeded with living human cells or with cells of other species. Further, the invention encompasses fusing the particulates to constitute composites of various shapes, or holding them together in a porous container made of membranous biopolymers. The particulates or composites can be used as tissues for grafting or as model systems for research and testing. The invention also encompasses the spinning of threads in which the matrix particulates are components.

Abstract: Single and double density biopolymer foams, composite biopolymer foams including both single and double density foams, and methods of preparing these foams and composite foams are described. Also described are biocompatible constructs which include single or double density biopolymer foams and extracellular matrix particulates and methods of preparing these constructs. The foams, composite foams, and biocompatible constructs of the invention can be used in tissue repair and reconstruction.

Abstract: Apparatus and methods are disclosed for maturing a biopolymer tissue construct in vitro prior to use as a replacement construct in vivo as, for example, a graft, implant, or prosthesis. The tissue is seeded with specific cells, exposed to a maturation fluid, such as a synovial-like fluid containing hyaluronic acid, and subjected to selected conditioning and maturation forces, which can include frictional forces, shear forces, and compressive pressure. The tissue is mounted on a first support element and a second surface applies a selected force to the tissue. This maturation process occurs within a maturation chamber. The resultant matured replacement tissue construct is intended to provide a replacement tissue that is more readily integrable in vivo to produce a more durable and functional replacement tissue.