Polyphenol-mediated hyaluronic acid/tannic acid hydrogel with short gelation time and high adhesion strength for accelerating wound healing

Abstract

Wound healing is a complex process involving a complicated interplay between numerous cell types and vascular systems. Hyaluronic acid (HA)-based hydrogel facilitates wound healing, and is involved in all processes. However, slow gelation speed and weak adhesion strength limit its ability to form a stable physical barrier quickly. Herein, we propose a HA-based composite hydrogel as the wound dressing based on oxidative coupling reaction. Tannic acid and dopamine-coated carbon particles (DCPs) containing abundant phenolic hydroxyl groups are incorporated into the HA-based hydrogel for increasing the number of crosslinking sites of oxidative coupling of the hydrogel and enhancing adhesion through the formation of covalent bonds and hydrogen bonds between hydrogel and wound sites. The composite hydrogel exhibits short gelation time (<6 s) and high adhesion strength (>8.1 kPa), which are superior to the references and commercial products of its kind. The in vitro experiments demonstrate that the hydrogel has low hemolytic reaction, negligible cytotoxicity, and the ability to promote fibroblast proliferation and migration. The in vivo full-thickness skin defect model experiments demonstrate that the hydrogel can accelerate wound healing under mild photothermal stimulation of DCPs by reducing inflammation, relieving tissue hypoxia, and promoting angiogenesis and epithelialization.