HUMAN OSTEOBLAST RESPONSE IN-VITRO TO PLATELET-DERIVED GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA DELIVERED FROM CONTROLLED-RELEASE POLYMER RODS
Hd. Kim et Rf. Valentini, HUMAN OSTEOBLAST RESPONSE IN-VITRO TO PLATELET-DERIVED GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA DELIVERED FROM CONTROLLED-RELEASE POLYMER RODS, Biomaterials, 18(17), 1997, pp. 1175-1184
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.