pH-Responsive Hydrogel with Dual-crosslinked Network of Polyvinyl Alcohol/Boric Acid for Controlled Release of Salvianolic Acid B: Novel Pro-Regenerative Mechanisms in Scar Inhibition and Wound Healing

Abstract This study investigates a novel pH-responsive hydrogel composed of polyvinyl alcohol (PVA) and boric acid (BA) designed for the controlled release of salvianolic acid B (SAB), addressing the critical challenge of scar formation and skin regeneration. The dual-crosslinked network architecture of the hydrogel exhibits remarkable pH sensitivity, enabling it to achieve a peak SAB release within 48 hours in the acidic microenvironment characteristic of early-stage wound healing. In vitro assessments demonstrated that the PVA-BA-SAB hydrogel significantly inhibits fibroblast activation and mitigates abnormal collagen deposition, effectively preventing excessive scar formation. Transcriptome sequencing reveals the potential role of PVA-BA-SAB hydrogel in balancing TGF-β and Wnt signaling pathways. Furthermore, in vivo studies revealed enhanced tissue regeneration, characterized by improved collagen organization and increased vascularization, as well as the promotion of mature hair follicle development. The hydrogel’s biocompatibility, mechanical robustness and adhesive properties were also thoroughly evaluated, confirming its suitability for clinical applications. These findings suggest that the PVA-BA-SAB hydrogel fully exerts the excellent characteristics of biomaterials and maximizes the pharmacological effect of SAB. Our innovative drug delivery system not only facilitates enhanced wound healing but also offers a strategic approach to minimize scarring. This research provides valuable insights into innovative therapeutic strategies for effective wound management and tissue repair.