Investigation into the release of bioactive recombinant human growth hormone from normal and low-viscosity poly(methylmethacrylate) bone cements

Abstract

Previous studies showed that recombinant human growth hormone (hGH) released from hormone-loaded poly(methylmethacrylate) (PMMA) cement stimulated osteoid formation in a rabbit model. Local delivery of hGH from cemented hip arthroplasties may thereby provide a means of reducing the problem of aseptic loosening. We have investigated two different formulations of PMMA as delivery systems for bioactive hGH. The bioactivity of the hormone release in vitro was monitored with an eluted stain assay (ESTA). The hGH was also measured by an immunoassay, which provides an alternative assessment of structural integrity of the hormone released. In addition, we adapted the ESTA bioassay to assess the in vitro cytotoxicity of the cements. Using unloaded cements, the undiluted eluates from both types of PMMA proved cytotoxic. This cytotoxicity could be diluted out, and the procedure allowed us to measure the bioactivity of hGH in the eluates from hormone-loaded cements independent of their cytotoxicity. The major fraction of the bioactivity was released from both of the PMMA cements during the first 24 h, but the hormone remained detectable in eluates collected after 36 days of elution. Comparison of the bio- and immunoactivity of the hGH released showed that the ratio of these two activities (i.e., the B:I ratio) was constant over this time period. However in parallel studies in which hormone-loaded discs were stored under dry conditions prior to elution, we found that the B:I ratio then declined markedly. This suggests that fully hydrated conditions, such as when the discs are bathed in assay medium, are necessary to maintain the bioactivity of the hGH. Both cements released only approximately 1% of the hormone originally incorporated, but the hGH concentration which accumulated in the eluates were high in physiologic terms (approximately 1000 mU/L).

The in vitro bioactivity of two novel hydrophilic, partially degradable bone cements

“…a material that is able to establish a direct bond to bone [6]. Although bone particles [7,8] and growth hormones [9,10] have been used for this, bioactive glasses [11] or glassceramics [12,13] and hydroxylapatite (HA) [14][15][16] are the most promising and studied fillers. Besides imparting bioactive character to the cements, these fillers additionally improved compressive, tensile and flexural properties.…”

Influence of Nano-HA Coated Bone Collagen to Acrylic (Polymethylmethacrylate) Bone Cement on Mechanical Properties and Bioactivity

“…Many studies of PMMA-based cements have attempted to enhance interface crosslinking. Current research ideas mainly include three strategies: (a) adding partially biodegradable materials, such as polyhydroxyalkenonate (PHA) and poly-β-hydroxybutyrate (PHB)[ 52 , 53 ]; (b) adding completely biodegradable materials to commercial PMMA or modified PMMA, such as sodium fluoride[ 54 , 55 ], nanoscale aluminum oxide (average size of 70nm)[ 56 ], cellulose[ 57 , 58 ] and tricalcium phosphate ceramic (TCP)[ 59 ]; and (c) adding bioactive materials to commercial PMMA or modified PMMA, such as apatite wollastonite glass (AWG)[ 60 , 61 ], hydroxyapatite (HA) [ 62 , 63 ] and recombinant growth factor [ 64 ]. In all of these studies, the formation of pores and the induction and adsorption properties were responsible for improvements in interface crosslinking.…”

Alternative acrylic bone cement formulations for cemented arthroplasties: Present status, key issues, and future prospects

“…The first comprises cements in which a bioactive agent is blended with the cement powder of a PMMA cement. Examples of fillers are particles of hydroxyapatite (HA);140–142 MgO‐CaO‐SiO 2 ‐P 2 O 5 ‐CaF 2 (apatite wollastonite) glass (AWG)143, 144; recombinant human growth hormone145; strontium‐containing HA146–149; and HA + chitosan 137…”