1. ¹Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester, Rochester, New York, USA
2. ²Department of Biomedical Engineering, University of Rochester, Rochester, New York, USA
3. ³Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Rochester, Rochester, New York, USA
4. ⁴Department of Orthopedics, Aarhus University Hospital, Denmark

Correspondence: Hani A. Awad, The Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, New York 14642, USA. E-mail: hani_awad@urmc.rochester.edu

The first two authors contributed equally to this work.

Received 29 August 2007; Accepted 29 November 2007; Published online 8 January 2008.

Abstract

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-Gdf5 -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.