PDGF-BB released in tendon repair using a novel delivery system promotes cell proliferation and collagen remodeling

• Published in: Journal of orthopaedic research 2007-10, Vol.25 (10), p.1358-1368
• Main Authors: Thomopoulos, Stavros, Zaegel, Melissa, Das, Rosalina, Harwood, Fredrick L., Silva, Matthew J., Amiel, David, Sakiyama-Elbert, Shelly, Gelberman, Richard H.
• Format: Article
• Language: English
• Subjects: Angiogenesis Inducing Agents - administration & dosage; Animals; Cell Proliferation - drug effects; Cells, Cultured; Collagen - metabolism; Combined Modality Therapy; delivery system; Dipeptides - metabolism; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Drug Delivery Systems; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; flexor tendon; growth factor; Platelet-Derived Growth Factor - administration & dosage; Proto-Oncogene Proteins c-sis; Recombinant Proteins - administration & dosage; sustained delivery; Sutures; tendon healing; Tendon Injuries - drug therapy; Tendon Injuries - surgery; Tendons - drug effects; Tendons - metabolism; Tendons - pathology; Wound Healing - drug effects
• ISSN: 0736-0266; 1554-527X
• DOI: 10.1002/jor.20444

The purpose of this study was to promote fibroblast proliferation and collagen remodeling in flexor tendon repair through sustained delivery of platelet derived growth factor (PDGF‐BB). The release kinetics of PDGF‐BB from a novel fibrin matrix delivery system was initially evaluated in vitro. After the in vivo degradation rate of the fibrin matrix was determined using fluorescently tagged fibrin, PDGF‐BB was delivered to the site of flexor tendon repair in vivo in a canine model. The effect of PDGF‐BB on intrasynovial tendon healing was studied using histology‐based assays (cell density, proliferation, and type I collagen expression) and by measuring total DNA levels and reducible collagen crosslink levels. The fibrin matrix delivery system provided sustained release of PDGF‐BB in vitro at a rate modulated by the ratio of heparin to growth factor. In vivo, the fibrin matrix remained at the repair site for more than 10 days. Delivery of PDGF‐BB led to a qualitative increase in cell density, cell proliferation, and type I collagen mRNA expression. PDGF‐BB also led to statistically significant increases in total DNA (20% increase at 7 days, 18% increase at 14 days) and reducible collagen crosslinks (30% increase at 7 days). Sustained delivery of growth factors may be achieved using a novel fibrin‐based delivery system. PDGF‐BB delivery increased cell proliferation and matrix remodeling and thus may accelerate flexor tendon healing. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1358–1368, 2007