Controlled-release kinetics and biologic activity of platelet-derived growth factor-BB for use in flexor tendon repair.
OBJECTIVE
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.
Sakiyama-Elbert
Shelly E
SE
Department of Orthopaedic Surgery, Washington University in St. Louis, St. Louis, MO, USA.
Das
Rosalina
R
Gelberman
Richard H
RH
Harwood
Fredrick
F
Amiel
David
D
Thomopoulos
Stavros
S
D043925:Angiogenesis Inducing Agents / Q000493:pharmacokinetics*; D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D066298:In Vitro Techniques; D023421:Models, Animal; D010982:Platelet-Derived Growth Factor / Q000493:pharmacokinetics*; D020574:Proto-Oncogene Proteins c-sis; D013708:Tendon Injuries / Q000628:therapy*; D014945:Wound Healing / Q000187:drug effects*
D043925:Angiogenesis Inducing Agents; D016326:Extracellular Matrix Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D005337:Fibrin; D003094:Collagen