Wound-Healing Biodegradable Microparticles: An In Vitro Investigation

Abstract

Wound healing is a complex process that may result in healthy tissue regeneration, but problematic chronic wounds exhibit fibrosis and persistent inflammation. To improve wound outcomes, we investigated the application of pro-proliferative polymers as bioresorbable particles for the first time. The surface of bioresorbable poly(D, L lactic acid) (PDLLA) microparticles are decorated with a pro- and anti-proliferative polymer. Microparticles with a pro-proliferative polymer surface chemistry, increase fibroblast proliferation in an in vitro wound healing model. The cells are found to move to establish bridges between the microparticles, which facilitate cell elongation and proliferation, which we postulate contributes to healing in vivo. Proteomics of the extracted proteins from particle surface identifies proteins adsorbed uniquely to pro-proliferative polymer surface chemistries, including annexin, olfactomedin 4 and vimentin. The roles of these proteins in healing from the literature are highlighted to gain mechanistic insight into the wound-healing stimulation of these bioresorbable particles. The lipid deposition/retention from exposure to culture media of microparticles is investigated by 3D OrbiSIMS showing that preferential adsorption of lipid, including sterols, fatty acids and sphingolipid, correlates with pro and anti-healing polymers. This mechanistic insight helps advance this technology to address the pressing issue of chronic wound healing. This collection contains data related to in vitro tests conducted in the manuscript.