Controlled-release kinetics and biologic activity of platelet-derived growth factor-BB for use in flexor tendon repair.

PURPOSE: Surgically repaired intrasynovial tendons are at greatest risk of failure in the first 3 weeks after surgery. Attempts to improve the strength of repair by modifying rehabilitation parameters have not always been successful. Manipulation of the biological environment of the sutured tendon holds great promise for accelerating the repair process. The goals of this study were to examine (1) the range of conditions (eg, dosage, delivery system formulation, presence of cells) over which delivery of platelet-derived growth factor-BB (PDGF-BB) can be sustained from fibrin matrices using a heparin-binding delivery system (HBDS) and (2) the biological activity of the PDGF-BB released from this system on canine tendon fibroblasts in vitro. METHODS: We examined in vitro release kinetics from cellular and acellular fibrin matrices using enzyme-linked immunosorbent assays. We examined the biologic activity of the PDGF-BB in vitro by measuring cell proliferation (ie, total DNA) and collagen synthesis (ie, proline incorporation). RESULTS: The acellular release kinetics of PDGF-BB was modulated by varying the ratio of PDGF-BB to heparin (PDGF-binding sites) or the dose of PDGF-BB in the presence of the delivery system. In the presence of canine tendon fibroblasts, the delivery system prolonged the duration of PDGF-BB release from fibrin matrices, thus demonstrating that cells are able to liberate PDGF-BB retained by the HBDS. Sustained delivery of PDGF-BB promoted increased cell proliferation at doses of 0.125 microg/mL and 1.25 microg/mL compared to fibrin without delivery system. Collagen synthesis was enhanced by PDGF-BB at doses of 0.125 microg/mL and 1.25 microg/mL; however, there was an enhancement over fibrin without the delivery system only at the lower dose. CONCLUSIONS: These results demonstrate that the PDGF-BB released from fibrin matrices containing an HBDS is biologically active and can modulate both cell proliferation and extracellular matrix synthesis, both of which are key factors in the process of tendon repair.

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

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.