Heparin-loaded hierarchical fiber/microsphere scaffolds for anti-inflammatory and promoting wound healing

Chronic, non-healing wounds that are induced by oxidative stress and inflammation generate inflammatory cell activation and produce enormous amounts of inflammatory mediators, thereby failing to maintain skin homeostasis and delaying the wound-healing process. To tackle this issue, we prepared heparin-loaded hierarchical composite scaffolds comprised of electrospinning fibers and electrospraying microspheres to act as an effective anti-inflammatory wound dressing. To improve surface topographical cues and cellular activities, we tested several microsphere densities deposited into the surface of the electrospun fibers. The results indicated that electrospraying the fibers for 3 min resulted in the best performance in terms of promoting cellular activities, with no obvious cytotoxicity, good adhesion morphology, and the fastest cell migration rate. In addition, a suitable amount of heparin was added to the composite scaffolds to alleviate inflammation. The significant adsorption efficiency observed from the heparin-loaded composite scaffolds on the inflammatory mediator MCP-1 indicates that the scaffolds produced an anti-inflammation effect in vitro. Furthermore, the heparin-loaded hierarchical scaffolds accelerated the pace of inflammatory wound healing in vivo when compared to commercial 3 M Tegaderm and non-heparin-loaded scaffolds. Our work provided a facile strategy for fabricating heparin-loaded hierarchical fiber/microsphere scaffolds to modulate cellular activities via topographical cues and accelerating the inflammatory wound healing process by electrostatic interactions between heparin and MCP-1. These findings suggested that the heparin-loaded hierarchical scaffold was expected to be a promising dressing for inflammatory wound healing.