Degradative behaviour of polymeric matrices in (sub)dermal and muscle tissue of the rat: a quantitative study

Bilayered matrices, made of synthetic degradable polymers, are developed for use as a dermal regeneration template in large surface area full-thickness skin defects. The porous underlayer is designed to allow ingrowth of dermal components and the dense top layer will serve as a substrate for keratinocytes. Considering the importance of the degradation kinetics of tissue regeneration templates, quantification of matrix degradation up to 1 yr post-implantation, and histological and ultrastructural examination of the implants was performed. In this study a moderate foreign body reaction was observed at both the intramuscular and subcutaneous implantation sites, including the presence of mono- and multinucleated phagocytes. Poly(L-lactic acid) underlayers tended to elicit a stronger cellular infiltrate than co-polymeric ones. In the course of the implantation periods this inflammatory response subsided and neovascular ingrowth and the formation of fibrous tissue in the pores was observed. Matrix degradation was demonstrated, starting with the fragmentation of the constituent polymers into increasingly smaller particles. During the implantation period, fragments showed progressive surface erosion. Poly(L-lactic acid) fragments had a more rounded off appearance as compared to co-polymeric ones. Implant surface area had decreased to less than 20%, 1 yr post-implantation. At both implantation sites and with all matrices, polymer particles were observed inside phagocytic cells. Degradation kinetics were similar with the different matrices. Implants fragmented more rapidly at the subcutaneous implantation site as compared to the intramuscular one. Although the data suggest biomaterial degradation, remnants of matrices could still be retrieved 1 yr post-implantation.