Freeze-dried tendon allografts as tissue-engineering scaffolds for Gdf5 gene delivery.
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.
Basile
Patrick
P
Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester, Rochester, New York 14642, USA.
Dadali
Tulin
T
Jacobson
Justin
J
Hasslund
Sys
S
Ulrich-Vinther
Michael
M
Søballe
Kjeld
K
Nishio
Yasuhiko
Y
Drissi
M Hicham
MH
Langstein
Howard N
HN
Mitten
David J
DJ
O'Keefe
Regis J
RJ
Schwarz
Edward M
EM
Awad
Hani A
HA
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology*; D000229:Dependovirus / Q000235:genetics; D005612:Freeze Drying; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D055428:Growth Differentiation Factor 5; D007150:Immunohistochemistry; D007592:Joint Diseases / Q000235:genetics / Q000628:therapy*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D013710:Tendons / Q000637:transplantation*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014161:Transduction, Genetic; D014184:Transplantation, Homologous; D014945:Wound Healing / Q000235:genetics / Q000502:physiology
D019485:Bone Morphogenetic Proteins; C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5