INVESTIGATION INTO THE RELEASE OF BIOACTIVE RECOMBINANT HUMAN GROWTH-HORMONE FROM NORMAL AND LOW-VISCOSITY POLY(METHYLMETHACRYLATE) BONE CEMENTS

Previous studies showed that recombinant human growth hormone (hGH) re leased from hormone-loaded poly(methylmethacrylate) (PMMA) cement stim ulated osteoid formation in a rabbit model. Local delivery of hGH from cemented hip arthroplasties may thereby provide a means of reducing t he problem of aseptic loosening. We have investigated two different fo rmulations of PMMA as delivery systems for bioactive hGH. The bioactiv ity of the hormone release in vitro was monitored with an eluted stain assay (ESTA). The hGH was also measured by an immunoassay, which prov ides an alternative assessment of structural integrity of the hormone released. In addition, we adapted the ESTA bioassay to assess the in v itro cytotoxicity of the cements. Using unloaded cements, the undilute d eluates from both types of PMMA proved cytotoxic. This cytotoxicity could be diluted out, and the procedure allowed us to measure the bioa ctivity of hGH in the eluates from hormone-loaded cements independent of their cytotoxicity. The major fraction of the bioactivity was relea sed from both of the PMMA cements during the first 24 h, but the hormo ne remained detectable in eluates collected after 36 days of elution. Comparison of the bio- and immunoactivity of the hGH released showed t hat the ratio of these two activities (i.e., the B:I ratio) was consta nt over this time period. However in parallel studies in which hormone -loaded discs were stored under dry conditions prior to elution, we fo und that the B:I ratio then declined markedly. This suggests that full y hydrated conditions, such as when the discs are bathed in assay medi um, are necessary to maintain the bioactivity of the hGH. Both cements released only similar to 1% of the hormone originally incorporated, b ut the hGH concentration which accumulated in the eluates were high in physiologic terms (similar to 1000 mU/L). (C) 1997 John Wiley & Sons, Inc.