Magnesium-EGCG composite deer antler decellularized ECM hydrogel for diabetic wound healing

Abstract

Diabetic wound healing remains a major clinical challenge, primarily due to excessive inflammation, bacterial infection, and impaired angiogenesis. Although various biomaterial-based strategies have been explored, coordinating the complex diabetic wound microenvironment remains difficult to achieve. This study proposes a novel multifunctional hydrogel dressing designed to synergistically address multiple issues. Its key innovation lies in dynamically crosslinking deer antler decellularized matrix (dECM) with oxidized dextran via imine bonds, creating a self-healing hydrogel (dECMH). The deer antler dECM, rich in pro-regenerative components, provides a biomimetic scaffold, while Schiff base crosslinking confers mechanical self-healing and injectability. To further address the complexity of diabetic wounds, magnesium gallate metal-organic frameworks (Mg-EGCG) were embedded within the dECMH network, forming Mg-EGCG@dECMH. This innovative combination enables sustained co-delivery of epigallocatechin gallate (EGCG)—possessing antibacterial, anti-inflammatory, and antioxidant properties—alongside magnesium ions that actively promote cell proliferation and vascular regeneration. In vitro analyses confirmed the hydrogel's capacity to enhance endothelial cell proliferation, boost angiogenesis, and mitigate oxidative stress. In vivo evaluations demonstrated accelerated wound healing, manifested by rapid inflammation resolution, ordered collagen deposition, and stimulated neovascularization. Additionally, the material exhibited excellent biocompatibility, hemostatic effects, and antimicrobial activity. This multifunctional dressing synergistically integrates the inherent bioactivity of unique antler decellularized matrix with the multimodal therapeutic effects of metal-organic nanocomposites, offering an innovative and effective strategy for diabetic wound management.