A smart ROS-responsive hydrogel for on-demand antibacterial and platelet-rich plasma (PRP) activation in diabetic wound healing.

Diabetic infected wounds present a significant clinical challenge due to persistent infection, chronic inflammation, and impaired angiogenesis. To address this, we developed a novel photo-crosslinked double-network hydrogel (HTC/MCP) by integrating phenylboronic acid-modified hyaluronic acid, a calcium tannate network, methacrylated carboxymethyl chitosan, and platelet-rich plasma (PRP). This smart hydrogel features reactive oxygen species (ROS)-responsiveness. Under high ROS conditions, it rapidly dissociates to release calcium ions and tannic acid-which acts as an antioxidant and anti-inflammatory agent. These components work synergistically to provide robust antibacterial efficacy (>99 % inhibition against S. aureus and E. coli in vitro) and, crucially, to activate PRP in situ for the sustained release of growth factors (VEGF, PDGF, EGF). The hydrogel demonstrated excellent injectability, self-healing, and biocompatibility. In vitro, it significantly enhanced fibroblast migration and angiogenesis. In a diabetic rat infected wound model, HTC/MCP treatment achieved nearly 95 % wound closure by day 14, significantly outperforming the control group (∼65 %). It also effectively reduced bacterial load, suppressed inflammation, and promoted collagen deposition. This multifunctional hydrogel thus represents a potent and promising strategy for treating complex diabetic wounds.