Heparinized PGA host-guest hydrogel loaded with paracrine products from electrically stimulated adipose-derived mesenchymal stem cells for enhanced wound repair

The microenvironment of the wound bed is essential in the regulation of wound repair. In this regard, strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes. Herein, we attempted to use electrical stimulation (ES) to boost the paracrine function of adipose-derived stem cells from rats (rASCs). By examining the concentrations of two important growth factors, VEGF and PDGF-AA, in the cell culture supernatant, we found that ES, especially 5 μA ES, stimulated rASCs to produce more paracrine factors (5 μA-PFs). Further studies showed that ES may modulate the paracrine properties of rASCs by upregulating the levels of TRPV2 and TRPV3, thereby inducing intracellular Ca²⁺ influx. To deliver the PFs to the wound to effectively improve the wound microenvironment, we prepared a heparinized PGA host-guest hydrogel (PGA-Hp hydrogel). Moreover, PGA-Hp hydrogel loaded with 5 μA-PFs effectively accelerated the repair process of the full-thickness wound model in rats. Our findings revealed the effects of ES on the paracrine properties of rASCs and highlighted the potential application of heparinized PGA host-guest hydrogels loaded with PFs derived from electrically stimulated rASCs in wound repair.