Enzyme-Mimetic Hydroxyapatite for Diabetic Wound Dressing with Immunomodulation and Collagen Remodeling Functions

Wound dressing is expected to provide protection and a regenerative environment for healing. For diabetic chronic wounds, the characteristic persistent oxidative stress and impaired collagen remodeling present additional challenges. Hydroxyapatite (HAp) with inherent biocompatibility is newly found to have a collagen-stimulating capacity for matrix remodeling. On the other hand, nanoenzyme-like carbon dots (CDs) are feasible for anti-inflammatory and antioxidative stress applications. Inspired by the shared high-temperature synthesis conditions of HAp and CDs, we developed a one-step hydrothermal method to fabricate iron-doped CDs-functionalized HAp (CDs-HAp) to integrate the collagen-stimulating bioactivity of HAp and the multienzyme activity of Fe-CDs. By embedding the CDs-HAp into a biomimetic hydrogel film of dual-cross-linked silk fibroin (DSF), we created a flexible and adhesive wound dressing (CDs-HAp@DSF) with robust ROS scavenging and immunomodulatory functions. We demonstrated that CDs-HAp@DSF can facilitate fibroblast proliferation and collagen synthesis while mitigating oxidative damage and promoting macrophage polarization toward the anti-inflammatory M2 phenotype. In vivo, it accelerates diabetic wound healing by synergistically enhancing collagen deposition, suppressing pathological inflammation, and reshaping the regenerative immune microenvironment. This design leverages matrix remodeling and enzymatic ROS elimination to concurrently target oxidative stress, inflammation, and ECM dysregulation, offering a potential therapeutic strategy for chronic diabetic wound healing.