Rock Climbing-Inspired Electrohydrodynamic Cryoprinting of Micropatterned Porous Fiber Scaffolds with Improved MSC Therapy for Wound Healing

Impaired wound healing imposes great health risks to patients. Recently, mesenchymal stem cell (MSC) therapy has shown potential to improve the healing process, but approaches to employ MSCs in the treatment of wounds remain elusive. In this study, we reported a novel electrohydrodynamic (EHD) cyroprinting method to fabricate micropatterned fiber scaffolds with polycaprolactone (PCL) dissolved in glacial acetic acid (GAC). Cyroprinting ensured the formation of a porous structure of PCL fibers by preventing the evaporation of GAC, thus increasing the surface roughness parameter Ra from 11 to 130 nm. Similar to how rough rocks facilitate easy climbing, the rough surface of fibers was able to increase the adhesion of adipose-derived MSCs (AMSCs) by providing more binding sites; therefore, the cell paracrine action of secreting growth factors and chemokines was enhanced, promoting fibroblast migration and vascular endothelial cell tube formation. In rat models with one-centimeter wound defects, enhanced MSC therapy based on porous PCL fiber scaffolds improved wound healing by augmenting scarless collagen deposition and angiogenesis and reducing proinflammatory reactions. Altogether, this study offers a new and feasible strategy to modulate the surface topography of polymeric scaffolds to strengthen MSC therapy for wound healing. Graphic Abstract