Cj. Goodwin et al., INVESTIGATION INTO THE RELEASE OF BIOACTIVE RECOMBINANT HUMAN GROWTH-HORMONE FROM NORMAL AND LOW-VISCOSITY POLY(METHYLMETHACRYLATE) BONE CEMENTS, Journal of biomedical materials research, 34(1), 1997, pp. 47-55
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.