Comprehensive hydrolytic degradation study of a new poly(ester-amide) used for total meniscus replacement

Abstract

Total meniscus replacement scaffolds composed of a collagen-hyaluronan sponge reinforced with poly(desaminotyrosyl-tyrosine dodecyl dodecanedioate) (poly(DTD DD)) fibers support formation of functional neo-meniscus tissue in a sheep model. Poly(DTD DD) is a new polymer that was specifically designed to meet the required mechanical properties while exhibiting a high degree of biocompatibility. Extensive in vivo studies confirmed the overall success of this device. To ensure adequate healing, poly(DTD DD) was intentionally designed to be a very slowly degrading polymer: at two years post-implantation, some residual poly(DTD DD) fibers remained at the implant site. In order to understand the mechanism and the kinetics of poly(DTD DD) degradation, a comprehensive degradation study was carried out under physiological and accelerated conditions. Using accelerated degradation methods (elevated temperature, organic cosolvent, and enzyme), the degradation pathway, end-stage degradation products, and rates of degradation were determined. The degradation of desaminotyrosyl-tyrosine dodecyl ester (DTD) monomer was studied using a variety of esterases and proteases for their activity and stability. Porcine pancreas lipase (PP-L) was found to be the most effective enzyme for DTD degradation. Of all the conditions tested, the temperature-accelerated method (60°C) showed the fastest degradation rate of poly(DTD DD) fibers; after about 40 weeks, poly(DTD DD) retained less than 6% of its initial number average molecular weight (Mn). In contrast, 58%, 43%, and 53% of the original number average molecular weight (Mn) was retained after 40 weeks under solvent-accelerated (methanol:water mixture, 37°C), enzyme-accelerated (PP-L, 37°C), and physiological conditions (37°C), respectively. Resorbable degradation products were first observed after the polymer fibers degraded to about 22% of their initial Mn, corresponding to a residual Mn of 19 kDa. Elucidation of the complete degradation mechanism has provided important information necessary for the use of this innovative polymer for meniscus replacement and in other medical devices.