HUMAN OSTEOBLAST RESPONSE IN-VITRO TO PLATELET-DERIVED GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA 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-deri ved growth factor (PDGF-BB) and/or transforming growth factor-beta 2 ( TGF-beta 2) on human osteoblast proliferation and differentiation. Hum an osteoblasts were plated in vitro and proliferation and protein synt hesis 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 proli feration and no effect on protein synthesis. EVA-TGF-beta 2 rods relea sing about 23 ng per ml per day increased protein synthesis but had no effect on proliferation. PDGF and TGF-beta 2 together resulted in mod erate increases in proliferation and a marked increase in protein synt hesis. Morphologically, PDGF-treated cells became confluent as early a s 48 h, while TGF-beta 2-treated cells formed into nodules. This work shows that (1) it is possible to deliver physiological levels of bioac tive proteins from an extrudable EVA delivery system, and (2) bone cel l response is dependent on the sequence and timing of delivery. Contro lled-release delivery systems which mimic injury-induced heating casca des may be useful in evaluating the role of various molecules in osseo us repair. (C) 1997 Elsevier Science Limited. All rights reserved.