Human osteoblast response in vitro to platelet-derived growth factor and transforming growth factor-β delivered from controlled-release polymer rods

The purpose of this work was (1) to develop extrudable ethylene-vinyl acetate (EVA) copolymer delivery systems capable of sustained release of bioactive proteins and (2) to determine the effect of platelet-derived growth factor (PDGF-BB) and/or transforming growth factor-β2 (TGF-β2) on human osteoblast proliferation and differentiation. Human osteoblasts were plated in vitro and proliferation and protein synthesis assayed at 48 and 96 h. EVA-PDGF rods releasing about 34 ng per ml PDGF per day produced a dramatic early increase in osteoblast proliferation and no effect on protein synthesis. EVA-TGF-β2 rods releasing about 23 ng per ml per day increased protein synthesis but had no effect on proliferation. PDGF and TGF-β2 together resulted in moderate increases in proliferation and a marked increase in protein synthesis. Morphologically, PDGF-treated cells became confluent as early as 48 h, while TGF-β2-treated cells formed into nodules. This work shows that (1) it is possible to deliver physiological levels of bioactive proteins from an extrudable EVA delivery system, and (2) bone cell response is dependent on the sequence and timing of delivery. Controlled-release delivery systems which mimic injury-induced healing cascades may be useful in evaluating the role of various molecules in osseous repair.