Electrospun Acid-Neutralizing Fibers for Improved Biocompatibility

Abstract

Biodegradable aliphatic polyesters, especially polylactide (PLA), polyglycolide (PGA), and their copolymer poly(lactide-co-glycolide) (PLGA), are the most representative and widely used synthetic polymers in the field of tissue engineering and regenerative medicine. However, these polyesters often give rise to the aseptic inflammation problem triggered by their acidic degradation products after implantation. Here, shell-core structured unidirectional fibers of chitosan/poly(lactide-co-glycolide) (i.e., CTS/PLGA) with acid-neutralizing capability were proposed for addressing the noted issue so as to achieve improved biocompatibility. Our results showed that during a period of 8-week degradation, the shell-layer of chitosan with its unique alkaline nature for acid-neutralization obviously hindered pH decrease as a result of the degradation of PLGA-core. In a mocked acidic environment testing with the human dermal fibroblasts, chitosan-enabled acidity neutralization could significantly reduce in vitro the secretion of inflammatory factors and down-regulate the expression of related inflammatory genes, such as Interleukin-6 (IL-6) and Interleukin-8 (IL-8) in the fibroblasts. Thereafter, biocompatibility assesments in vitro showed that CTS/PLGA nanofibers had poorer cell adhesion capacity than PLAG nanofibers, but were cytocompatible and promoted the cell migration and secretion of collagen. Moreover, two and four weeks of subcutaneous embedding in vivo revealed that the CTS/PLGA nanofibers significantly reduced the recruitment of inflammatory cells and the formation of foreign body giant cells (FBGCs). This study thereby demonstrated the excellent acid-neutralizing effect of the chitosan-coating layer on alleviating the inflammatory response caused by the acidic degradation products of the PLGA-core. Our highly-aligned CTS/PLGA nanofibers, as a kind of quasi ‘pH-neutral fibers’ with acid-neutralizing capability, may be potentially applied for engineering those architecturally anisotropic tissues (e.g., tendon/ligament) toward improved efficacy of regeneration.

Keywords: Chitosan, PLGA, Electrospinning, Acidic degradation products, Inflammatory response, Biocompatibility