Natural multi-active nanoparticles integrated biological hydrogel microcarriers for wound healing

Bioactive substance-integrated hydrogels have demonstrated efficacy in diabetic wound treatment. However, challenges remain in identifying naturally derived, multifunctional active substances capable of addressing the complex pathophysiology of wounds, as well as in tailoring hydrogels to enhance their suitability for wound applications. Here, we present a novel biological hydrogel microcarrier system by integrating Bletilla striata-derived nanoparticles (PdNPs) and polydopamine nanozymes (PDAs) into a hyaluronic acid-methacrylate (HAMA) hydrogel. PdNPs can polarize over-activated macrophages to an anti-inflammatory phenotype and restore fibroblast functionality. Meanwhile, PDAs act as potent reactive oxygen species (ROS) scavengers and protect fibroblasts from oxidative stress-induced apoptosis. When encapsulated into HAMA microcarriers, the PdNP + PDA@HAMA microcarriers significantly accelerate wound healing in a diabetic rat model. These outcomes demonstrate the therapeutic potential of our natural, multifunctional hydrogel microcarriers as a promising wound dressing platform for the treatment of chronic diabetic wounds.