Wound-healing biodegradable microparticles: an <i>in vitro</i> investigation

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, the application of pro-proliferative polymers as bioresorbable particles was investigated for the first time. The surface of bioresorbable poly(D,L-lactic acid) (P_DLLA) microparticles is decorated with a pro- and anti-proliferative polymer that adheres to the surface for a minimum of 21 days. Microparticles with a pro-proliferative polymer surface chemistry have been shown to increase fibroblast proliferation <i>in vitro</i> by 5 fold after 48 hours compared to cells without microparticle treatment. The cells are found to move to establish bridges between the microparticles, which facilitate cell elongation and proliferation, accelerating a key stage of the wound healing cycle. Adsorbed proteins were examined using proteomics, and unique proteins were found to adhere to microparticles exhibiting proliferative surface chemistry. These proteins include annexin, olfactomedin 4 and vimentin, and the roles of these proteins have been highlighted to gain a mechanistic insight into the stimulated proliferative environment caused by the microparticles. The lipid deposition/retention from exposure to the culture media of microparticles was investigated using 3D Orbi-SIMS and highlights preferential adsorption of lipids, including sterols, fatty acids and sphingolipids, which correlates with pro- and anti-healing polymers. This mechanistic insight helps advance this technology to address the pressing issue of chronic wound healing.