Investigating the Biodegradation Mechanism of Poly(trimethylene carbonate): Macrophage-Mediated Erosion by Secreting Lipase

Poly(trimethylene carbonate) (PTMC), as one of the representatives of biodegradable aliphatic polycarbonates, has been found to degrade in vivo via surface erosion. This unique degradation behavior and the resulting nonacidic products make it more competitive with aliphatic polyesters (e.g., polylactide) in clinical practice. However, this surface degradation mechanism is complicated and not fully understood to date despite the findings that several reactive oxygen species and enzymes can specifically degrade PTMC in vitro. Herein, the biodegradation mechanism of PTMC was investigated by using possible degradation factors, distinct cell lines, and the inhibitors of these factors. The results demonstrate that PTMC undergoes a specific macrophage-mediated erosion. Macrophages tend to fuse into giant cells and elicit a typical inflammatory response by releasing proinflammatory cytokines. In addition, macrophages are suggested to primarily secrete enzymes (lipase specifically) to erode the PTMC bulk extracellularly as inhibiting their activity effectively prevented this eroding process. The clarification of the biodegradation mechanism in this work suggests that the degradation of PTMC highly depends on the foreign body response. Thus, it reminds the researchers to consider the effect of the microenvironment on the degradation and drug release of PTMC-based implantation devices and localized drug delivery systems.