In vitro growth factor release from injectable calcium phosphate cements containing gelatin microspheres

To improve the in vivo resorption of an injectable calcium phosphate cement (CPC) for bone tissue engineering purposes, in previous experiments macroporosity was introduced by the in situ degradation of incorporated gelatin microspheres. Gelatin microspheres are also suitable carriers for osteoinductive drugs/growth factors, where release occurs concomitantly with degradation of the hydrogel. Introduction of these microspheres into CPC can alter the release pattern of the cement, which usually shows a marginal release of incorporated drugs. The goal of this study was to determine the in vitro release characteristics of gelatin microsphere CPC. For this, recombinant human TGF-beta1, bFGF, and BMP-2 were labeled with (125)I and loaded onto gelatin type A (porcine, pI = 7.0-9.0)/type B (bovine, pI = 4.5-5.0) microspheres for a short (instant) and longer (prolonged) time before mixing them with the cement. Radioactivity of the resulting 5 or 10 wt % gelatin microsphere CPC composites was monitored for 6 weeks when subjected to proteolytic medium. Drug-loaded CPC was used as control. Results showed that release pattern/efficiency of gelatin microsphere CPCs and CPC controls was highly dependent on the type of growth factor but unaffected by the amount of growth factor. With gelatin microsphere CPC, release was also dependent on the type of gelatin, total volume of incorporated microspheres, and loading method.