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Show moreBackground of the invention: In the context of skeletal tissue repair, tissue regeneration therapy is the local application of autologous (host-derived) cells to promote reconstruction of tissue defects caused by trauma, disease or surgical procedures. The objective of the tissue regeneration therapy approach is to deliver high densities of repair-competent cells (or cells that can become competent when influenced by the local environment) to the defect site in a format that optimizes both initial wound mechanics and eventual neotissue production. For soft tissue repair, it is likely that an implant vehicle(s), will be required to 1) transport and constrain the autologous cells in the defect site and 2) provide initial mechanical stability to the surgical site. In an optimal system, it is likely that the vehicle will slowly biodegrade at a rate comparable to the production of neotissue and development of strength in the reparative tissue (1). The tissue regeneration therapy approach contrasts significantly with more passive approaches to wound repair in which no attempt is made to deliver or to recruit reparative cells to the defect site. For example, in the case of anterior cruciate ligament (ACL) repair with synthetic (presumably "inert") polymer grafts, the healing process depends entirely on local cellular responses to initiate and control the incorporation of a permanent implant (2). Recently, more active devices have been tested using matrix scaffolds designed to deliver and/or to direct cellular processes. These have included tendon or ACL repair (3-7), meniscus repair (8-11) and articular cartilage repair (12-15). Alternatively, the use of locally delivered peptide factors, intended to stimulate recruitment of reparative cells and their attachment and/or differentiation, have also been investigated (16-19). In perhaps the best documented tendon repair experiments to date, Silver, Dunn and their colleagues have described extensive investigations of the performance of collagen fiber prostheses for Achilles tendon (3-5) and anterior cruciate ligament (ACL) (6,7) repair in rabbits. They report that at 52 weeks postimplantation in the Achilles tendon defect, the reconstructed tendon (prosthesis+repair tissue) was about 66% as strong as the normal tissue for all implants tested, including an autologous tendon graft and glutaraldehyde- or carbodiimide-crosslinked collagen fiber composites (5). Both the autologous implants and the carbodiimide-crosslinked prostheses were observed to biodegrade rapidly, then regain strength rapidly as new tissue was produced. Glutaraldehyde cross-linked prostheses biodegraded much more slowly in the Achilles tendon model and became surrounded by a thick capsule that eventually stopped the degradation process. While the neotendon developed in these studies was similar to normal, it was not identical.
http://www.google.com/patents?vid=USPAT5855619
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Show moreCross reference to related applications: Of interest is commonly owned copending application U.S. Ser. No. 09/039,127 entitled "Uses for Human Mesenchymal Stem Cells" filed Mar. 13, 1998 in the name of Bruder et al. and incorporated by reference in its entirety herein. Background of the invention: In the context of skeletal tissue repair, tissue regeneration therapy is the local application of autologous (host-derived) and allogeneic (non-host derived) cells to promote reconstruction of tissue defects caused by trauma, disease or surgical procedures. The objective of the tissue regeneration therapy approach is to deliver high densities of repair-competent cells (or cells that can become competent when influenced by the local environment) to the defect site in a format that optimizes both initial wound mechanics and eventual neotissue production. For soft tissue repair, it is likely that an implant vehicle(s), will be required to 1) transport and constrain the autologous cells in the defect site and 2) provide initial mechanical stability to the surgical site. In an optimal system, it is likely that the vehicle will slowly biodegrade at a rate comparable to the production of neotissue and development of strength in the reparative tissue (1). The tissue regeneration therapy approach contrasts significantly with more passive approaches to wound repair in which no attempt is made to deliver or to recruit reparative cells to the defect site. For example, in the case of anterior cruciate ligament (ACL) repair with synthetic (presumably "inert") polymer grafts, the healing process depends entirely on local cellular responses to initiate and control the incorporation of a permanent implant (2). Recently, more active devices have been tested using matrix scaffolds designed to deliver and/or to direct cellular processes. These have included tendon or ACL repair (3-7), meniscus repair (8-11) and articular cartilage repair (12-15). Alternatively, the use of locally delivered peptide factors, intended to stimulate recruitment of reparative cells and their attachment and/or differentiation, have also been investigated (16-19). In perhaps the best documented tendon repair experiments to date, Silver, Dunn and their colleagues have described extensive investigations of the performance of collagen fiber prostheses for Achilles tendon (3-5) and anterior cruciate ligament (ACL) (6,7) repair in rabbits. They report that at 52 weeks postimplantation in the Achilles tendon defect, the reconstructed tendon (prosthesis+repair tissue) was about 66% as strong as the normal tissue for all implants tested, including an autologous tendon graft and glutaraldehyde--or carbodiimide-crosslinked collagen fiber composites (5). Both the autologous implants and the carbodiimide-crosslinked prostheses were observed to biodegrade rapidly, then regain strength rapidly as new tissue was produced.
http://www.google.com/patents?vid=USPAT6174333
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