A macrophage culture model was used to investigate the erosion of gamma irradiated poly(trimethylene carbonate) (PTMC) films. When the PTMC films were incubated in the culture medium, but physically separated from the cells by a membrane, no erosion occurred. In contrast, when the J774A macrophages were directly cultured on PTMC films, they adhered to the films and were found to have eroded the polymer surface. Macrophages adhered to gamma irradiated poly(E-caprolactone) (PCL) controls as well, but to a lesser extent than to the PTMC films. In this case, no signs of erosion were observed. Human skin fibroblasts cultured on PTMC and PCL films as controls also adhered to the films but did not erode the surfaces. The effect of enzymes and reactive oxygen species that can be secreted by macrophages on the erosion process was assessed using aqueous solutions of cholesterol esterase, lipoprotein lipase, esterase, potassium superoxide, and hydrogen peroxide. The PTMC films eroded in aqueous enzyme solutions as well as in aqueous superoxide solutions. Cholesterol esterase and superoxide anion radicals seem to be most involved in the macrophage-mediated erosion of PTMC. This macrophage culture model is useful in assessing the influence of macrophages on the in vivo biodegradability of polymers and in elucidating the biodegradation mechanisms involved. (C) 2009 Elsevier Ltd. All rights reserved.