Journal
MOLECULAR THERAPY
Volume 16, Issue 3, Pages 466-473Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.mt.6300395
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Funding
- NIAMS NIH HHS [AR054041, P50 AR054041, P50 AR054041-030004, R01 AR051469-01, R01 AR051469, AR051469] Funding Source: Medline
- NIDCR NIH HHS [R21 DE017096-02, DE017096, R21 DE017096] Funding Source: Medline
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Tendon reconstruction using grafts often results in adhesions that limit joint flexion. These adhesions are precipitated by inflammation, fibrosis, and the paucity of tendon differentiation signals during healing. In order to study this problem, we developed a mouse model in which the flexor digitorum longus (FDL) tendon is reconstructed using a live autograft or a freeze-dried allograft, and identified growth and differentiation factor 5 (Gdf5) as a therapeutic target. In this study we have investigated the potential of rAAV-df5-loaded freeze-dried tendon allografts as therapeutically endowed tissue-engineering scaffolds to reduce adhesions. In reporter gene studies we have demonstrated that recombinant adeno-associated virus (rAAV)-loaded tendon allografts mediate efficient transduction of adjacent soft tissues, with expression peaking at 7 days. We have also demonstrated that the rAAV-Gdf5 vector significantly accelerates wound healing in an in vitro fibroblast scratch model and, when loaded onto freeze-dried FDL tendon allografts, improves the metatarsophalangeal (MTP) joint flexion to a significantly greater extent than the rAAV-lacZ controls do. Collectively, our data demonstrate the feasibility and efficacy of therapeutic tendon allograft processing as a novel paradigm in tissue engineering in order to address difficult clinical problems such as tendon adhesions.
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