IN-VIVO DEGRADATION AND BIOCOMPATIBILITY STUDY OF IN-VITRO PRE-DEGRADED AS-POLYMERIZED POLYLACTIDE PARTICLES

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 r elated with a subcutaneous swelling in patients 3 yr postoperatively. In order to avoid these complications, polymers were developed that ar e anticipated to have comparable mechanical properties but a higher de gradation rate and do not degrade into highly stable particles that ca n induce a subcutaneous swelling. On chemical grounds it can be expect ed that copolymerization of PLLA with 4% D-lactide (PLA96) or by modif ying PLLA through cross-linking (CL-PLLA) will lead to less stable par ticles and a higher degradation rate. To evaluate the long-term suitab ility of these as-polymerized polymers, the biocompatibility of the de gradation products should be studied. Considering the very slow degrad ation rate of as-polymerized PLLA, in vitro pre-degradation at elevate d temperatures was used to shorten the in vivo follow-up periods. In t his study, the biocompatibility and degradation of as-polymerized PLLA , PLA96 and CL-PLLA were investigated by implanting pre-degraded parti culate materials subcutaneously in rats. Animals were killed after a p ostoperative period varying from 3 to 80 wk. Light and electron micros copical analysis and quantitative measurements were performed. The his tological response of all three pre-degraded materials showed a good s imilarity 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 pa rticle size and an enhanced degradation rate compared to PLLA. Based o n the chemical and quantitative analysis, the degradation of PLA96 and CL-PLLA was much more enhanced and thus more favourable than the degr adation of PLLA.