Abstract: The present invention relates to protein matrix materials and devices and the methods of making and using protein matrix materials and devices. More specifically the present invention relates to protein matrix materials and devices that may be utilized for various medical applications including, but not limited to, drug delivery devices for the controlled release of pharmacologically active agents, encapsulated or coated stent devices, vessels, tubular grafts, vascular grafts, wound healing devices including protein matrix suture material and meshes, skin/bone/tissue grafts, biocompatible electricity conducting matrices, clear protein matrices, protein matrix adhesion prevention barriers, cell scaffolding and other biocompatible protein matrix devices. Furthermore, the present invention relates to protein matrix materials and devices made by forming a film comprising one or more biodegradable protein materials, one or more biocompatible solvents and optionally one or more pharmacologically active agents.

Abstract: Systems and methods are provided for controlling the diameter of a mammalian hybrid coronary bypass graft. The system includes a controller having at least one input for receiving information and feedback information and an output for outputting control signals, including at least one steady flow system control signal; and a pressure/flow loop subsystem coupled to the controller. The pressure/flow loop subsystem includes a specimen holder, an external flow loop system coupled to the specimen holder, a steady flow system, and an output for outputting the feedback information. The pressure/flow loop subsystem receives the control signals and is capable of adjusting a diameter of a specimen in accordance with the control signals, when the specimen holder contains the specimen.

Abstract: Developing heart valves are exposed to dynamic strains by applying a dynamic pressure difference over the leaflets. The flow is kept to a minimum, serving only as a perfusion system, supplying the developing tissue with fresh nutrients. Standard heart valves were engineered based on B trileaflet scaffolds seeded with cells isolated from the human saphenous vein. Tissue compaction is constrained by the stent, inducing increasing pre-strain in the tissue. The dynamic strains the tissues are exposed to via the dynamic pressure difference, are estimated using finite element methods based on the mechanical properties of the neo-tissue, in order to get inside into the strain distribution over the leaflet.

Abstract: A biological nerve guide for implantation into a human body is made by providing a natural animal tissue membrane, crosslinking and fixing the membrane, minimizing the antigens from the membrane, tanning the membrane, coupling an active layer to an inner surface of the membrane, cutting the membrane into a desired shape and size, positioning the cut membrane onto a rod-shaped mold so that the cut membrane assumes a cylindrical configuration, and attaching a spiral support to the outer surface of the cut membrane.

Abstract: Described herein are tissue grafts derived from the placenta. The grafts are composed of at least one layer of amnion tissue where the epithelium layer has been substantially removed in order to expose the basement layer to host cells. By removing the epithelium layer, cells from the host can more readily interact with the cell-adhesion bio-active factors located onto top and within of the basement membrane. Also described herein are methods for making and using the tissue grafts. The laminin structure of amnion tissue is nearly identical to that of native human tissue such as, for example, oral mucosa tissue. This includes high level of laminin-5, a cell adhesion bio-active factor show to bind gingival epithelia-cells, found throughout upper portions of the basement membrane.

Abstract: A prosthetic heart valve includes an annular stent having annularly spaced commissure portions. The tips of the commissure portions are preferably covered with fabric, and then additional fabric covers that fabric and the remainder of the stent, both inside and out (possibly also including a sewing ring insert at or near the base or inflow edge). The fabric is then covered by a layer of tissue, again both inside and out. A single sheet of additional tissue is mounted around the outside of the previously assembled components. This additional tissue forms the leaflet portions of the valve. The leaflet portions of the additional tissue are shaped by contact with a shaped mandrel, and the tissue of the structure is subjected to fixation (e.g., cross-linking) to produce a completed valve.

Abstract: An organ support apparatus includes: (a) a fluid circuit defining upstream and downstream legs adapted to be connected to an organ to be supported; (b) a circulation pump connected to the fluid circuit for circulating a process fluid through the fluid circuit and the organ; and (c) a first waveform generator connected to the fluid circuit for impressing a preselected pressure waveform on the process fluid.

Abstract: A system for hemodynamic simulation comprises a vessel having properties of a blood vessel, a reservoir containing a quantity of fluid, tubing connecting the vessel and reservoir, and at least one pump for circulating the fluid within the system. Fluid can be tissue culture medium or blood analog fluid, and the vessel may include mammalian cells attached to its inside. A drive system, comprising two reciprocating drive shafts that are coupled by a cam, enables the uncoupling of pulsatile flow and pulsatile pressure to provide independent control over wall shear stress and circumferential strain. The shaft drives two pumps that are 180 degrees out-of-phase and are connected upstream and downstream of the vessel, and effect this uncoupling.

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 coat a hybrid graft with a confluent monolayer of endothelial cells by immobilizing stem cells on a hybrid hemodialysis access graft or a hybrid femoral artery bypass graft, and placing the hybrid graft in a system embodiment according to the invention under conditions effective to promote the stem cells to form a confluent monolayer on the hybrid graft and in an environment to promote the stem cells to differentiate into endothelial cells.

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: 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: 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.

Abstract: Non-glutaraldehyde fixation of an organ or a prosthesis for implantation in a mammal is based upon carbodiimide treatment. A solution containing a sterilizing agent, such as EDC, in combination with a coupling enhancer, such as Sulfo-NHS, and a high concentration of a diamine cross linking agent is used. As a result, only minimal surface reduction occurs during fixation, and the resultant products show a dramatic increase in resistance to calcification.

Abstract: A bioreactor and a method for growing engineered tissue provide facing surfaces in a vessel for containing cell-culture media. The facing surfaces are equidistant and define a gap therebetween while providing substrates for cell tissue growth. By maintaining conditions within the vessel conducive to cell tissue growth and moving the surfaces relative to one another within such cell culture media, tissue growing thereupon is subjected to physiological flow and shear stress, preferably through the use of oscillating motion, and engineered tissue is produced.

Abstract: A prosthesis for implantation into a human body is made by a method that includes the steps of providing a natural animal ligament or tendon that has a substrate, crosslinking and fixing the substrate, minimizing the antigens from the substrate, tanning the substrate to improve its mechanical properties, and coupling an active layer to the substrate.

Abstract: Methods and structures are disclosed where carrier fiber is used to enable the assembly of two and three dimensional structures of autologous tissue. Tissue is harvested from the donor, integrated with a carrier fiber, and assembled into complex forms rapidly. The structures can be tailored to the requirements of a specific medical procedure. The tissue is kept live and viable during extracorporeal assembly and the finished structure is emplaced in the donor's body. The use of a carrier fiber leader for pre-threading integration and assembly machines facilitates machine set up, drawing of the tissue into the process, and rapid integration and assembly of the multi-dimensional structures. Assembly can include providing tissue and fiber leaders extending from the structure for attaching the structure in place. The carrier fiber either is bio-absorbed as new tissue forms, or forms a bio-compatible substructure for the patient's native tissue.

Abstract: Apparatus and methods for seeding an implantable medical device, such as a vascular prosthesis, with cells, such as endothelial cells, are described. The invention supports techniques for seeding a luminal surface of the device with axial centrifugation. Cells are introduced in suspension into the lumen of the device. The introduction of the cells may occur after a blood centrifugation product, such as platelet-poor plasma, is applied to the luminal surface. After the cells are introduced, the device is then subjected to centrifugation around a longitudinal axis defined by the lumen. Axial centrifugation causes the cells to concentrate toward and adhere to the luminal surface. Shortly after axial centrifugation, the seeded device can be presented for implantation in a patient. The implantable medical device may be inserted into a protective sleeve prior to seeding the device with cells, and the sleeve may or may not be removed prior to implantation.

Abstract: Apparatus and methods for seeding an implantable medical device, such as a vascular prosthesis, with cells, such as endothelial cells, are described. The invention supports techniques for seeding a luminal surface of the device with axial centrifugation. Cells are introduced in suspension into the lumen of the device. The introduction of the cells may occur after a blood centrifugation product, such as platelet-poor plasma, is applied to the luminal surface. After the cells are introduced, the device is then subjected to centrifugation around a longitudinal axis defined by the lumen. Axial centrifugation causes the cells to concentrate toward and adhere to the luminal surface. Shortly after axial centrifugation, the seeded device can be presented for implantation in a patient. The implantable medical device may be inserted into a protective sleeve prior to seeding the device with cells, and the sleeve may or may not be removed prior to implantation.

Abstract: A cell culture assembly and a method for culturing cells that provide mechanical stimulation to cells. The cell culture assembly can include a flow chamber positioned in a fluid path and a support comprising cells positioned within the flow chamber to expose the cells to the fluid path. The cell culture assembly can further include a means for producing a steady flow of fluid in the fluid path, and a means for producing an oscillatory flow of fluid in the fluid path simultaneously with producing the steady flow of fluid in the fluid path to mechanically stimulate the cells. The method can include transporting fluid in the fluid path at a substantially steady flow rate, and transporting fluid in the fluid path at a substantially oscillatory flow rate simultaneously with transporting fluid in the fluid path at a substantially steady flow rate.

Abstract: A prosthesis for implantation into a human body is made by a method that includes the steps of providing a natural animal ligament or tendon that has a substrate, crosslinking and fixing the substrate, minimizing the antigens from the substrate, tanning the substrate to improve its mechanical properties, and coupling an active layer to the substrate.

Abstract: A method of preparing a fixed biological tissue includes, shaping the biological tissue, cross-linking the biological tissue, sterilizing the biological tissue, and inactivating prions in the biological tissue.

Abstract: A cell/tissue culture apparatus for applying a desired tensile stress to a material to be cultivated such as a cell or tissue as a physical stimulation, thereby enhancing acceleration of culture of the material to be cultivated. The cell/tissue culture apparatus comprises a chamber (a culture chamber 8) for circulating a culture fluid (24), a material to be cultivated (a matrix 32) that is placed and cultivated in the chamber, stress generation means (an electromagnetic stretcher 38, an actuator 56) for causing a tensile stress to act on the material to be cultivated from an outside of the chamber, and control means (controllers 50, 60) for causing the tensile stress generated by the stress generation means to intermit as well as undergo gradual increase or gradual decrease. The material to be cultivated can be caused to undergo expansion or contraction by applying and relieving the tensile stress, thereby applying a physical stimulation necessary for the proliferation to the material to be cultivated.

Abstract: A cell/tissue culture apparatus is suitable for a culture of a cultivated object of a cell or tissue adapted for a prescribed portion of a living body of a breast and so on, a culture chamber (18, a culture vessel 10) which accommodates a cell or tissue to be cultivated and also makes a culture fluid (34) circulate is formed by a flexible material (flexible films 12, 14), and the culture chamber is immersed in a fluid (water 8). A pressure or an oscillation is given to the culture chamber installed in the fluid, and a physical stimulation due to the pressure from the fluid or the oscillation of the fluid is given to a cell or tissue under a culture.

Abstract: A treatment for bioprosthetic tissue used in implants or for assembled bioprosthetic heart valves to reduce in vivo calcification is disclosed. The method includes preconditioning, pre-stressing, or pre-damaging fixed bioprosthetic tissue in a manner that mimics the damage associated with post-implant use, while, and/or subsequently applying a calcification mitigant such as a capping agent or a linking agent to the damaged tissue. The capping agent suppresses the formation of binding sites in the tissue that are exposed or generated by the damage process (service stress) and otherwise would, upon implant, attract calcium, phosphate, immunogenic factors, or other precursors to calcification. The linking agent will act as an elastic reinforcement or shock-absorbing spring element in the tissue structure at the site of damage from the pre-stressing.

Abstract: The sterilization of biological material of animal or human origin, which is to be used as an implant or transplant, is performed according to a validated sterilization method with a margin of safety of 106 germs by which harmful microorganisms are physically separated and chemically sterilized in four successive steps, initially in an antibiotic, then in deoxicholic acid, then in a surface-active substance and finally in primary alcohol, respectively accompanied by rinsing steps involving an aqueous solution after steps two to four. A bioprosthesis sterilized with a margin of safety>106 germs can be implanted without any further treatment, does not have a tendency towards calcification, and ensures a long service life.

Abstract: The present invention provides processes for fixation of biological tissue and/or post-fixation treatment of such tissue that result in modified tissues with reduced susceptibility to in vitro calcification when used in prosthetic devices. The invention also relates to calcification resistant biological tissue and to methods of using such tissue.

Abstract: A bioreactor and methods of using same for making tissue constructs and for conditioning tissue-engineered constructs and harvested tissues such as cryopreserved tissues. The bioreactor allows for static and dynamic culture/conditioning. The bioreactor is dual chambered (one chamber above and one below the cells or construct) to allow for application of biochemical and/or biomechanical stimuli to each side of the cells/construct.

Abstract: Transplantation of epithelial stem cells, cultured ex vivo on specifically treated amniotic membrane, yields, with that amniotic membrane, a surgical graft having expanded epithelial stem cells. The method of creating this graft and the graft itself are simple and effective to reconstruct damaged tissue, a preferred example being corneal tissue. The source of the epithelial stem cells can be a very small explant from healthy autologous and allogeneic tissue biopsy. The amniotic membrane is treated such that its extracellular matrix is maintained, but its cells are killed.

Abstract: A microprocessor controlled and instrumented bioreactor for conditioning intravascular tissue engineered medical products. One bioreactor design including an integrated pump to provide a relatively small volume of fluid nutrient. The microprocessor control providing measurement and control of the fluid flow and tissue displacement and subsequent determination of material properties. One design includes a flexible joint providing motion of the treated tissue in the axial, bending and torsional direction.

Abstract: In some embodiments, a flow system includes a medical device mount, fluid and a conduit containing the fluid and medical device mount. The conduit is mounted on an assembly that moves the conduit along with the medical device mount to induce relative motion of the fluid relative to the medical device mount. In preferred embodiments, pulsatile fluid motion is generated. In some embodiments, the fluid includes viable cells. In alternative embodiments, a flow system includes a continuous flow pump connected to a conduit loop having multiple branch conduits downstream from the pump providing alternative paths over a section of the conduit loop. Each branch conduit has a valve controlling flow through the branch. In some embodiments, at least one branch includes a medical device mount.

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: The present invention relates to a new method of preparing acellularized, biocompatible, implantation material starting from a biological material. In particular, the present invention relates to a method of preparing biological material for implantation comprising (a) fixation of the biological material with an aldehyde and (b) detoxification/anticalcification of the fixed biological material, wherein the detoxification/anticalcification step makes use of a novel class of substances of formula: NH2—(CH2)n—X ??(I) wherein X is COOH, SO3H, PO3H2 and n is an integer from 2 to 6.

Abstract: A method of treating a biological tissue including contacting the biological tissue with an aqueous sterilizing solution, and maintaining the aqueous sterilizing solution at a temperature of about 50° C. for a time period of about 1 to 2 days. The method of treating a biological tissue may be utilized as a terminal sterilization step in a method for fixation of biological tissues, and bioprosthetic devices may be prepared by such fixation method. The fixation method may include 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 the terminal sterilization method. The aqueous sterilizing solution may be glutaraldehyde of about 0.625 weight percent buffered to a pH of about 7.4.

Abstract: An apparatus for high-throughput analysis of compound absorption in a controlled environment that closely resembles in-vivo conditions. The apparatus includes at least one tissue-receiving enclosure that is capable of interfacing (e.g., via transfer of fluids, electronically, etc.) with a variety of preparative devices and analytical instrumentation. In some variations, the tissue-receiving enclosure is formed from two housings, which, when engaged, have a capsular shape. The enclosure receives a tissue sample in the form of an un-everted or everted intestinal segment or tubular artificial membrane. The tissue sample is coupled to a generally cylindrical tissue support. The tissue support and the enclosure are axially aligned, and openings at the ends of the enclosure align with openings at the ends of the tissue support. Two feed fittings, one for each end of the enclosure, forcefully mate with the aligned openings in the housing and the tissue support.

Abstract: The objective of the present invention is to provide a collagen material that possesses physical properties to an extent that allows suturing while still maintaining the biochemical properties inherently possessed by collagen, and retains its shape for a certain amount of time even after application to the body; its production process; and, a medical material on which it is based, examples of which include a artificial tube for nerve, artificial tube for spinal cord, artificial esophagus, artificial trachea, artificial blood vessel, artificial valve or alternative medical membranes such as artificial endocranium, artificial ligaments, artificial tendons, surgical sutures, surgical prostheses, surgical reinforcement, wound protecting materials, artificial skin and artificial cornea, characterized by filling or having inside a substance having biocompatibility that can be degraded and absorbed in the body into a matrix of a non-woven fabric-like multi-element structure of collagen fibers having ultra-fine fiber

Abstract: A 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 patients 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, 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 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: The present invention provides methods for preparing tissue for incorporation into xenografts and bioprosthetic devices. The methods of the invention make use of supercritical fluids to remove infectious materials and chemical agents from tissues, as well as to permeate a tissue with a chemical agent (e.g. tanning, cross-linking, and bioactive agents).

Abstract: An apparatus (10) to grow cell cultures includes an anchor (14) potted to a flexible membrane (12) and an anchor stem (16) to which cells attach. A jig (18) having a trough (46) and at least one passage (52) is positioned adjacent the flexable membrane (12). A method for growing and mechanically conditioning three-dimensional cell constructs begins by drawing the flexible membrane (12) and the anchor stem (14) into the trough (46) by means (20) for flexing the flexible membrane (12) (step 114). Cells are supplied (step 116) and allowed to attach to the anchor stem (16) (step 118). The flexible membrane (12) is released from within the trough (46) (step 120), resulting in a three-dimensional structure (34) of cells attached to the anchor stem (16). The cells grow into the three-dimensional construct (step 130). The structure (34) and/or the construct can be subjected to a regimen of strain for mechanical conditioning of the cells (step 132).

Abstract: An apparatus and method that allows the visualization of leakage of cell culture media through a conduit wall of a tissue-engineered biological construct such as a semilunar heart valve or valve graft under controlled physiologic conditions. The apparatus and method also allows for the assessment of valve function and intraluminal flow using conventional imaging modalities such as ultrasonic and magnetic resonance imaging. The apparatus allows the qualitative and quantitative evaluation of structural and functional characteristics of a condition tissue engineered construct prior to implantation using a valve housing and chamber and a flow-pressure simulator.

Abstract: The invention features a bioreactor system. The system includes components, which exert physiologically relevant translational and rotational strains on a growing bioengineered tissue.

Abstract: The subject invention pertains to compositions and methods for culturing nerve tissue in vitro and nerve grafts produced using such methods. The compositions and methods of the subject invention can be employed to restore the continuity of nerve interrupted by disease, traumatic events or surgical procedures. The invention also concerns methods for promoting repair of damaged nerve tissue using the present compositions and nerve tissue treated according to such methods.

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: A method and apparatus for limiting longitudinal stretch during fixation of a harvested aortic root including valve leaflets and the product produced. The apparatus includes an inflow plug inserted into the inflow section of the aortic root and having an apertured tube or cannula extending through the valve leaflets to an outflow plug inserted into the outflow section of the aortic root. Apertures in the tube are located on either side of the valve leaflets and the tube is coupled to a fluid inlet, preferably located on the outflow plug. The outflow plug is slidable relative to the tube and is provided with an engagement mechanism such as a setscrew for fixing the location of the outflow plug relative to the tube and the inflow plug. After assembly of the aortic root to the apparatus, the fluid inlet is coupled to a source of defined pressure and the root is inflated.

Abstract: A method for preparing a soft tissue xenograft includes the steps of 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 either digesting the xenograft with a glycosidase or glycosidase digestion followed by treatment for sialylation. A soft tissue xenograft for implantation into a human includes a portion of a soft tissue from a non-human animal, wherein the portion has extracellular matrix and substantially only dead cells. The matrix and dead cells have substantially no surface &agr;-galactosyl moieties and have sialic acid molecules linked to at least a portion of surface carbohydrate moieties. Each of the xenografts of the invention has substantially the same mechanical properties as a corresponding native soft tissue.

Abstract: Living fibrocytes are combined with rotator cuff extracellular matrix obtained from recently deceased human or animal donors to eliminate pain in patients with tendonitis and other rotator cuff deficiencies. According to the method, fibrocytes from a living donor, preferably the patient, and rotator cuff tissue is harvested from a recently deceased human or animal donor in a manner which retains the extracellular matrix. The harvested cells are combined with the extracellular matrix to produce an engineered rotator cuff tissue, which is then transplanted into or onto a patient's rotator cuff to be repaired. Additional therapeutic substances such as culture medium, growth factors, differentiation factors, hydrogels, polymers, antibiotics, anti-inflammatory medications, or immunosuppressive medications could be added to the transplanted annulus fibrosis tissue.

Abstract: Living fibrocytes are combined with rotator cuff extracellular matrix obtained from recently deceased human or animal donors to eliminate pain in patients with tendonitis and other rotator cuff deficiencies. According to the method, fibrocytes from a living donor, preferably the patient, and rotator cuff tissue is harvested from a recently deceased human or animal donor in a manner which retains the extracellular matrix. The harvested cells are combined with the extracellular matrix to produce an engineered rotator cuff tissue, which is then transplanted into or onto a patient's rotator cuff to be repaired. Additional therapeutic substances such as culture medium, growth factors, differentiation factors, hydrogels, polymers, antibiotics, anti-inflammatory medications, or immunosuppressive medications could be added to the transplanted annulus fibrosis tissue.

Abstract: A method and apparatus of making repairs with graft ligaments. In one form, the method for graft ligament reconstruction comprises (i) harvesting a graft ligament consisting entirely of soft tissue; (ii) compacting the graft ligament through compression so as to significantly reduce the cross-sectional area and increase the density of the collagen material of the graft ligament; and (iii) deploying the compressed graft ligament in the human body. In another form, the apparatus for graft ligament reconstruction comprises a graft ligament having a given diameter and a given cross-sectional area; and a compacting instrument having at least one surface to contact the graft ligament and to decrease the given cross-sectional area of the graft ligament to a reduced cross-sectional area, whereby the graft ligament with the decreased cross-sectional area may be positioned within a bone tunnel having a cross-sectional area smaller than the given cross-sectional area of the graft ligament in its original state.

Abstract: An apparatus for treating fixed biological tissue to inhibit calcification of the biological tissue following implantation thereof in a mammalian body. The apparatus includes a container for placing the biological tissue in contact with a treatment solution, structure to induce relative tissue/solution movement, and structure to heat the solution. The relative movement may be induced by shaking a container in which the tissue is immersed in the treatment solution, or by stirring the solution within the container. The movement may also be induced by flowing a treatment solution past the tissue to be treated. The tissue may be free to move in the treatment container, or may be restrained from gross movements. The flow may be part of a circulation system having a reservoir, with a heater being provided to heat the treatment solution in the reservoir. Alternatively, a treatment apparatus, including a fluid circulation system if desired, may be enclosed in an incubator.