A multifunctional injectable hydrogel for boosted diabetic wound healing assisted by Quercetin-ZIF system

An important challenge in the chronic wound healing of diabetes is delayed healing stages with impaired cellular functions, attributed to mitochondrial dysfunction and excessive endoplasmic reticulum (ER) stress. Here, we describe a quercetin (QCT)-loaded zeolitic imidazolate framework (ZIF-8) incorporated into a polyphenol-mediated carboxymethyl chitosan/tannic acid (CT) dynamic hydrogel to promote diabetic wound healing by regulating subcellular and cellular functions. ZIF-8 endows the hydrogel with excellent antibacterial properties. By alleviating mitochondrial function and ER stress, the hydrogel fundamentally improves the cellular function damage induced by hyperglycemia and is endowed with reactive oxygen species (ROS)-scavenging and anti-apoptosis activities to promote cell proliferation, extension and keratinocyte differentiation. Moreover, sustained release of QCT and Zn2+ from the QCT@ZIF-8 system not only promotes vascular endothelial cell migration but also alleviates tubular dysfunction, thus achieving excellent angiogenesis. Accordingly, these features create a favorable environment for skin regeneration and synergistically accelerate diabetic wound healing. Therefore, our findings reveal a potential multi-effect therapeutic strategy for diabetic wound healing. Potential design principles targeting subcellular and cell function open up new avenues for other metabolic and inflammatory diseases.