Abstract: Described are tubular silk fibroin compositions and methods for their manufacture and use. Tubular compositions as described herein can be produced in a range of high burst strengths, can easily be made in a range of inner diameters, can be derivatized with functional moieties, and can be produced in a range of permeabilities suitable for particularized uses. In one aspect, the tubular compositions can be used in the repair or replacement of damaged or diseased blood vessels, including, but not limited to vessels smaller than about 6 mm.

Abstract: An anatomically-shaped, human bone graft may be cultivated ex vivo using a bioreactor capable of perfusing large complex porous scaffolds. Scaffolds derived from image-based modeling of a target are seeded with human mesenchymal stem cells and cultivated. A bioreactor configured to house complex three-dimensional scaffold geometries provides controlled flow for perfusion of the cells. Dense uniform cellular growth can be attained throughout the entire scaffold as a result of the medium perfusion. In an embodiment, the bioreactor has a mold into which perfusion medium is pumped under pressure and multiple ports through which the medium exits the mold.

Abstract: Disclosed are bioreactor devices, systems and methods. A bioreactor system can include one or more bioreactor modules that can be individually controllable and identifiable. A bioreactor module can be connected to one or more functional modules such as a pump module, a stimulation signal generation module, a motor module, a mechanical transmission module, a gas exchange module, a temperature module, a humidity module and/or a CO2 module, among others. The bioreactor and functional modules can include standard or universal connectors to facilitate connection and movement of modules. The bioreactor system can be controlled and/or monitored by a controller that can individually identify and control each connected module and that can be adapted to collect signal data from sensors embedded in any of the modules.

Abstract: A system and method for making a biomaterial device includes a support structure providing a shape for a biomaterial device. At least one applicator has a supply of biomaterial solution and is positioned along the support structure. The at least one applicator forms a biomaterial fiber by applying shear force to the biomaterial solution and delivering the biomaterial fiber to the support structure. A controller causes relative movement between the support structure and the at least one applicator, and the biomaterial fiber is arranged on the support structure according to the relative movement to form the biomaterial device. The biomaterial may be silk fibroin which may be wound onto a reciprocating and rotating mandrel. Control over the properties of the biomaterial device is achieved through appropriate selection of material processing, winding strategy, and post-winding processing.

Abstract: The present invention provides processes for producing porous silk fibroin scaffold material. The porous silk fibroin scaffold can be used for tissue engineering. The porosity of the silk fibroin scaffolds described herein can be adjusted as to mimic the gradient of densities found in natural tissue. Accordingly, methods for engineering of 3-dimensional tissue, e.g. bone and cartilage, using the silk fibroin scaffold material are also provided.

Abstract: The present invention provides processes for producing porous silk fibroin scaffold material. The porous silk fibroin scaffold can be used for tissue engineering. The porosity of the silk fibroin scaffolds described herein can be adjusted as to mimic the gradient of densities found in natural tissue. Accordingly, methods for engineering of 3-dimensional tissue, e.g. bone and cartilage, using the silk fibroin scaffold material are also provided.

Abstract: The invention is directed toward a cartilage repair assembly comprising a shaped structure of subchondral bone with an integral overlying cartilage cap which is treated to remove cellular debris and proteoglycans and milled cartilage in a bioabsorbable carrier. The shaped structure is dimensioned to fit in a drilled bore in a cartilage defect area so that said shaped bone and cartilage cap when centered in the bore does not engage the side wall of the bore in an interference fit and is surrounded by milled cartilage and carrier. A method for inserting the assembly into a cartilage defect area is disclosed.

Abstract: The invention is directed toward a cartilage repair assembly comprising a shaped structure of subchondral bone with an integral overlying cartilage cap which is treated to remove cellular debris and proteoglycans and milled cartilage in a bioabsorbable carrier. The shaped structure is dimensioned to fit in a drilled bore in a cartilage defect area so that said shaped bone and cartilage cap when centered in the bore does not engage the side wall of the bore and is positioned from the side wall of the bone a distance ranging from 10 microns to 1000 microns and is surrounded by milled cartilage and a fibrin thrombin glue. A method for inserting the assembly into a cartilage defect area is disclosed.

Abstract: The invention provides a method for forming an immobilized agent gradient within a 3-dimensional porous scaffold. A 3-dimensional scaffold formed from a biocompatible material is provided. The surface of the scaffold and/ or the agent is activated so as to allow binding of the agent to the scaffold. The activated scaffold is contacted with a solution containing the agent. Contact with the solution is maintained for a sufficient period of time to allow diffusion of the solution through a portion of the scaffold, thereby forming a desired gradient of the agent through the 3-dimensional scaffold.

Abstract: Tissue engineered constructs including a matrix and cells transfected with a gene for a growth factor. The constructs may be implanted into a tissue site, where the growth factor gene enhances a metabolic function furthering integration of the construct in the tissue site. If the matrix is biodegradable, the metabolic result may include resorption of the matrix and replacement with tissue synthesized at least in part by the transfected cells.

Abstract: Embryonic stem cells are propagated in a hyaluronic acid.

Abstract: The present invention provides processes for producing porous silk fibroin scaffold material. The porous silk fibroin scaffold can be used for tissue engineering. The porosity of the silk fibroin scaffolds described herein can be adjusted to mimic the gradient of densities found in natural tissue. Accordingly, methods for engineering of 3-dimensional tissue, e.g. bone and cartilage, using the silk fibroin scaffold material are also provided.

Abstract: The invention is directed toward a cartilage repair assembly comprising a shaped structure of subchondral bone with an integral overlying cartilage cap which is treated to remove cellular debris and proteoglycans and milled cartilage in a bioabsorbable carrier. The shaped structure is dimensioned to fit in a drilled bore in a cartilage defect area so that said shaped bone and cartilage cap when centered in the bore does not engage the side wall of the bore in an interference fit and is surrounded by milled cartilage and carrier. A method for inserting the assembly into a cartilage defect area is disclosed.

Abstract: The present invention provides new methods for the in vitro preparation of bioartificial tissue equivalents and their enhanced integration after implantation in vivo. These methods include submitting a tissue construct to a biomimetic electrical stimulation during cultivation in vitro to improve its structural and functional properties, and/or in vivo, after implantation of the construct, to enhance its integration with host tissue and increase cell survival and functionality. The inventive methods are particularly useful for the production of bioartificial equivalents and/or the repair and replacement of native tissues that contain electrically excitable cells and are subject to electrical stimulation in vivo, such as, for example, cardiac muscle tissue, striated skeletal muscle tissue, smooth muscle tissue, bone, vasculature, and nerve tissue.

Abstract: The invention relates to a tissue replacement structure comprising (a) a preformed three-dimensional tissue which can be produced by obtaining cells from a human or animal organism and culturing them in a stationary fashion as a suspension culture in cell culture vessels with hydrophobic surface and tapering bottom until a cell aggregate is formed which has differentiated cells embedded therein and has an outer region wherein cells capable of proliferation and migration are present; (b) (i) an autologous cell suspension which can be produced from endogenous cells, with endogenous serum being added, with no addition of growth-promoting compounds, (ii) implants or support materials and/or (iii) growth factors; and/or (c) can be obtained by exposure of the tissue according to (a) to electromagnetic fields, mechanical stimulation and/or ultrasound.

Abstract: The invention is directed toward a cartilage repair assembly comprising a shaped structure of subchondral bone with an integral overlying cartilage cap which is treated to remove cellular debris and proteoglycans and milled cartilage in a bioabsorbable carrier. The shaped structure is dimensioned to fit in a drilled bore in a cartilage defect area so that said shaped bone and cartilage cap when centered in the bore does not engage the side wall of the bore and is positioned from the side wall of the bone a distance ranging from 10 microns to 1000 microns and is surrounded by milled cartilage and a fibrin thrombin glue. A method for inserting the assembly into a cartilage defect area is disclosed.

Abstract: Compositions and methods comprising at least one active agent chosen from TGF-P superfamily proteins, including BMPs, and GDFs for increasing the growth rate or modulating the development of engineered cartilage are disclosed. The compositions are useful in the treatment of osteoarthritis, cartilage defects, and in related tissue repair.

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 present invention provides an improved method for expanding cells for use in tissue engineering. In particular the method provides specific biochemical factors to supplement cell culture medium during the expansion process in order to reproduce events occurring during embryonic development with the goal of regenerating tissue equivalents that resemble natural tissues both structurally and functionally. These specific biochemical factors improve proliferation of the cells and are capable of de-differentiation mature cells isolated from tissue so that the differentiation potential of the cells is preserved. The bioactive molecules also maintain the responsiveness of the cells to other bioactive molecules. Specifically, the invention provides methods for expanding chondrocytes in the presence of fibroblast growth factor 2 for use in regeneration of cartilage tissue.

Abstract: Tissue engineered constructs including a matrix and cells transfected with a gene for a growth factor. The constructs may be implanted into a tissue site, where the growth factor gene enhances a metabolic function furthering integration of the construct in the tissue site.