An in-vivo model to interrogate the transition from acute to chronic inflammation

This study describes the modulation of the rodent foreign body giant cell (FBGC) response to subcutaneously implanted, biodegradable poly(lactide-co-glycolide)/calcium phosphate (PLGA/CaP) composites by application of a thin surface coat of calcium phosphate. Macroporous PLGA/CaP composite scaffolds, with interconnecting macroporosity, were half coated with a 3mm thick layer of CaP by immersion in simulated body fluid. Half-coated scaffolds were implanted subcutaneously in the dorsum of male Wistar rats for 1, 4 and 8 weeks. Specimens were embedded in paraffin and tissue sections evaluated by light microscopy with particular reference to the FBGC response. Histomorphometry revealed that FBGCs were in contact with 6% (+/- 3.5%) of the uncoated half, at 1 week, but no FBGCs were seen on the coated half. By 4 weeks, FBGCs were seen on both the uncoated and coated halves of the scaffolds with 87% (+/-10%) and 36% (+/-4%) FBGC/polymer contact respectively. By 8 weeks these FBGC contact percentages had risen to 97% (+/-0.45%) in the case of the uncoated halves of scaffolds, but decreased to 22% (+/-4%) in the case of the CaP-coated halves. Thus the CaP coating abrogated the FBGC response to the underlying polymer. Such a model may prove useful in providing an experimental system whereby both the mechanisms of biocompatibility and the transition from acute to chronic inflammation could be interrogated.