Combined effect of SDF-1 peptide and angiogenic cues in co-axial PLGA/gelatin fibers for cutaneous wound healing in diabetic rats

Abstract

Skin regeneration is hindered by poor vascularization, prolonged inflammation, and excessive scar tissue formation, which necessitate newer strategies to simultaneously induce blood vessel regeneration, resolve inflammation, and induce host cell recruitment. Concurrent deployment of multiple biological cues to realize synergistic reparative effects may be an enticing avenue for wound healing. Herein, we simultaneously deployed SDF (stromal cell-derived factor)− 1α, VEGF (vascular endothelial growth factor)-binding peptide (BP), and GLP (glucagon like peptide)− 1 analog, liraglutide (LG) in core/shell poly(L-lactide-co-glycolide)/gelatin fibers to harness their synergistic effects for skin repair in healthy as well as diabetic wound models in rats. Microscopic techniques, such as SEM and TEM revealed fibrous and core/shell type morphology of membranes. Boyden chamber assay and scratch-wound assay displayed significant migration of HUVECs (human umbilical vein endothelial cells) in SDF-1α containing fibers. Subcutaneous implantation of membranes revealed higher cellular infiltration in SDF-1α loaded fibers, especially, those which were co-loaded with LG or BP. Implantation of membranes in an excisional wound model in healthy rats further showed significant and rapid wound closure in dual cues loaded groups as compared to control or single cue loaded groups. Similarly, the implantation of dressings in type 2 diabetes rat model revealed fast healing, skin appendages regeneration, and blood vessel regeneration in dual cues loaded fibers (SDF-1α/LG, SDF-1α/BP). Taken together, core/shell type fibers containing bioactive peptides significantly promoted wound repair in healthy as well as diabetic wound models in rats.