A Burning Grass and Removing Root Immunoregulatory Strategy Toward Chronic Wounds Therapy by MnO₂ Nanoparticle Incorporated Hyaluronic Acid Hydrogel

Abstract Complex immune microenvironment of diabetic wound possesses polarization misalignment of macrophages and excessive inflammatory response, which prolong the healing process. Consequently, developing hydrogel dressings with immunoregulatory ability shows huge potential in clinical management of diabetic wound. Nevertheless, recent immunoregulatory strategies are mainly focusing on switching the proinflammatory M1‐type to anti‐inflammatory M2‐type macrophages by using high‐cost dressings composed of cytokines and cells. Considering the hyperpolarized M1 macrophages of diabetic wounds as wild grass of wasteland, a burning grass and removing root immunoregulatory strategy toward wound healing is developed based on dopamine‐manganese dioxide nanoparticle incorporated high molecular weight hyaluronic acid (HHA) hydrogel. The self‐healing and injectable hydrogel is formed by boronate ester bonds between the HHA grafted with phenylboronic acid and polyvinyl alcohol. Notably, in vitro and vivo results confirm that the HHA components can burn the grass by switching M1 to M2 in the inflammatory microenvironment while the dopamine‐manganese dioxide nanoparticles can remove the root by relieving M1 polarization through eliminating reactive oxygen species. The comprehensive immunoregulation ability enables the hydrogel as effective therapeutic that improves wound healing, and shows reliable potential in clinical dressings for the management of diabetic wounds.