The degradation of high molecular weight as-polymerized poly(l-lactide) (PLLA) is very slow; it takes more than 5.6 yr for total resorption. Moreover, the degradation products of as-polymerized PLLA bone plates, consisting of numerous stable particles of high crystallinity, are related with a subcutaneous swelling in patients 3 yr postoperatively. In order to avoid these complications, polymers were developed that are anticipated to have comparable mechanical properties but a higher degradation rate and do not degrade into highly stable particles that can induce a subcutaneous swelling. On chemical grounds it can be expected that copolymerization of PLLA with 4% d-lactide (PLA96) or by modifying PLLA through cross-linking (CL-PLLA) will lead to less stable particles and a higher degradation rate. To evaluate the long-term suitability of these as-polymerized polymers, the biocompatibility of the degradation products should be studied. Considering the very slow degradation rate of as-polymerized PLLA, in vitro pre-degradation at elevated temperatures was used to shorten the in vivo follow-up periods. In this study, the biocompatibility and degradation of as-polymerized PLLA, PLA96 and CL-PLLA were investigated by implanting pre-degraded particulate materials subcutaneously in rats. Animals were killed after a postoperative period varying from 3 to 80 wk. Light and electron microscopical analysis and quantitative measurements were performed. The histological response of all three pre-degraded materials showed a good similarity with in vivo implanted material. Pre-degraded PLLA induced a mild foreign body reaction and showed a slow degradation rate. PLA96 and CL-PLLA had a substantially lower crystallinity, a smaller mean particle size and an enhanced degradation rate compared to PLLA. Based on the chemical and quantitative analysis, the degradation of PLA96 and CL-PLLA was much more enhanced and thus more favourable than the degradation of PLLA.

Animal model, As-polymerized polylactides, Biocompatibility, Biodegradation, In vitro pre-degradation,
Department of Pathology

Bergsma, J.E, Rozema, F.R, Bos, R.R.M, Boering, G, de Bruijn, W.C, & Pennings, A.J. (1995). In vivo degradation and biocompatibility study of in vitro pre-degraded as-polymerized polylactide particles. Biomaterials, 16(4), 267–274. doi:10.1016/0142-9612(95)93253-A