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Cell-Based Meniscal Repair Using an Aligned Bioactive Nanofibrous Sheath

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Technical Report,15 Jun 2015,14 Jun 2016

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The goal of this proposal is to develop a novel bio-activated, aligned, nanofibrous scaffold that will serve as mechanical and biological support for the repair of radial tears of the meniscus. The hypothesis is that scaffolds consisting of aligned polymeric fibers, which structurally and mechanically mimic tendon and fibrocartilage, may be applied as a patch in alignment with the fibers of the tissue to be repaired, i.e., the meniscus with radial tear, to strengthen mechanically the surgical meniscal repair, and to subsequently guide tissue regeneration, for example, by seeded tissue progenitor cells. To achieve this objective, the first step is to develop an aligned nanofibrous scaffold NFS that meets the mechanical requirements of the native meniscal matrix and provides suture retention. This will be done by combining nanofibers composed of FDA-approved biodegradable polymers to produce a biocompatible scaffold, which will provide mechanical support to the healing meniscus. To support suture retention, a second layer of non-aligned fibers will be coated onto the aligned fibers. Secondly, the NFS will be bio-enhanced by impregnation with an extract derived from decellularized meniscus matrix, which contains molecules and growth factors specific to this tissue, to increase the formation of fibrocartilage by adult stem cells seeded within the scaffold. This bio-activation should enhance the biological integration, i.e. adhesion, and tissue regenerating activity of the NFS in meniscus repair. Finally, we will test the ability of the bio-activated, aligned NFS sheath to enhance meniscus repair when combined with stem cell-based wound bonding strategies and standard suture repair using an in vitro model of meniscal repair employed to elucidate the optimal combination of materials developed here and in vivo, repairing surgically-induced radial defects in a goat.

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