Diffusion of Fibroblast Growth Factor from a Plaster of Paris Carrier

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DIFFUSION OF FIBROBLAST GROWTH FACTOR FROM A PLASTER OF PARIS CARRIER

Rosenblum, S., M.D., Frenkel, S., Ph.D., Ricci, J., Ph.D., and Alexander, H., Ph.D.

Department of Bioengineering Hospital for Joint Diseases Orthopaedic Institute 301 East 17th Street New York, NY 10003

INTRODUCTION Fibroblast growth factor (FGF) is a polypeptide found in two forms: basic and acidic. The basic form is produced by many more types of cells than the acidic form, although both bind to the same receptor. These proteins act on a variety of mesodermally and ectodermally derived cells, including chondrocytes, glial cells, myoblasts, endothelial cells, cornea and lens epithelia, adrenal cortical cells, ovarian granulosa cells, periosteal fibroblasts, and osteoblasts. 2,5.6- 14 ,18 Basic FGF was chosen for the present study for a variety of reasons. First, it has significant cross-species homology, with 98.7% correlation between human and both bovine and avian FGF. Less conservation has been observed in the acidic form. In addition, the basic form has been shown to be 30- to 100-fold more potent, depending on the target tissue.5

There is little in the literature on the effects of FGF on osseous tissue in vivo. One such

study, using a dose of 40 gg/ml, showed a significant early increase in angiogenesis and significantly decreased mineralization in a femoral defect; both effects had disappeared by 14 days. 15 Most of these studies have used either direct injections of FGF or implanted osmotic pumps for delivery of the FGF; both procedures, however, involve local trauma to the delivery site, which may interfere with the clinical interpretation of the results. In order to deliver the FGF in vivo, an appropriate delivery system must be found. Prerequsites for this system include biocompatibility, reliable release of the FGF, and noninterference with bone ingrowth.We have chosen calcium sulfate hemihydrate (plaster of Paris) because of its' property of excellent biocompatibility combined with relatively rapid dissolution which allow it to serve as a carrier for delivery of soluble substances in vivo.l1,3,4,16,17

The purpose of this study is to establish an understanding of the release of FGF from plaster of Paris. This characterization will form the basis for a planned in vivo study examining the effects of FGF on bone ingrowth and attachment to implant surfaces. The

Mat. Res. Soc. Symp. Proc. Vol. 252. '•11992 Materials Research Society

294

basic form of FGF will be used for the reasons outlined above. METHODS This study was divided into four experiments: I. II. III. IV.

FGF diffusion from PLP pellets FGF diffusion from PLP discs PLP dissolution in saline PLP dissolution in serum

I. FGF Diffusion from PLP Pellets in Saline

For this experiement, 0.6 cc of FGF solution in a 1:20 dilution (300 ng) was added to 2.000 g of CaSO4 hemihydrate powder ( J.T. Baker, Phillipsburg, NJ). This slurry was then placed into a mold to form pellets and allowed to dry in a vacuum dessicator for 48 hours. The pellets were then weighed individually and