Tissue Engineered Meniscus Repair

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DESCRIPTION (provided by applicant): Loss of the meniscus, in part or in total, greatly alters knee function and predisposes the joint to degenerative changes. The goal of this project is the repair or regeneration of critical-sized defects in the medial meniscus to restore meniscal function and prevent joint damage. Mesenchymal progenitor cells are potential repair cells for meniscal defects. In this study, autologous bone marrow-derived mesenchymal progenitor cells will used to create a fibrocartilaginous tissue in vitro that is then implanted for meniscal repair in vivo. The hypothesis to be tested is that tissue-engineered cartilage will provide a superior implant for meniscal repair. This will be tested in two different meniscal repair models: Specific Aim 1: To repair a surgically created mid-substance meniscal tear. The aim is to use a tissue-engineered cartilage to repair a surgically created tear in the medial meniscus. The cartilage will be created in vitro with autologous marrow-derived mesenchymal progenitor cells seeded into a biodegradable scaffold and cultured in a chondrogenic medium. The implant will be sutured into a full-thickness longitudinal tear. The repair potential of this tissue-engineered construct will be compared with those of empty scaffolds and no-implant sutured tears. Specific Aim 2: To regenerate meniscal tissue in a surgically created partial meniscectomy. A large tissue-engineered cartilaginous implant will be used to regenerate a partial meniscectomy of the goat medial meniscus. As for aim 1, the tissue-engineered implant will be composed of the biodegradable scaffold containing autologous mesenchynial progenitor cells, cultured in chondrogenic medium prior to implantation. For both aims, the meniscal implant will be analyzed at 12 weeks and 12 months after implantation. The operated knee joints will be subjected to biomechanical, morphological, histological and immunohistochemical analyses to provide a comprehensive assessment of the success of the tissue-engineering implants in the two repair models.