Abstract
Research in orthopaedics is now moving away from permanent metallic implants, and looking towards the use of bioresorbable polymers (e.g. PLLA, PGA and related co-polymers) that, when implanted into the injured site, bioresorb as the tissue heals. However, reports of a delayed inflammatory reponse occurring in the late stages of polymer degradation has limited the wide scale use of these polymers. Few studies assess the long-term biocompatibility of these polymers and with an increasing market for bioresorbable materials it is anticipated that this will be a future issue. This work aims to develop a predictive tool that can be used to assess the delayed inflammatory response of poly(D,L-lactide-co-glycolide) (PDLGA) using in vitro tests. An elevated temperature accelerated test (47oC) was developed and utilitised to induce predetermined amounts of degradation in PDLGA. This was used to mimic a range of clinically relevant in vivo implantation times up to 5–6 months. All pre-degradion work was performed under sterile conditions, in PBS solution. At predetermined time intervals, indicators of late stage inflammation will be assessed using an MTT cytotoxicity assay, an inflammation antibody array and an ELISA analysis for inflammatory factors, with mouse L929 fibroblasts, RAW264.7 and primary BMDM macrophages. It is hypothosised that at the later degradation time intervals signs of inflammatory factors will be observed. The methodologies developed in this work can be applied to the optimisation of polymer degradation profiles to minimise late-stage inflammatory repsonse and identification of beneficial additives in this regard.
