Thiol-ene photoclick hydrogels reinforced with poly(protocatechualdehyde)-coated gallium doped bioactive glass nanoparticles for scarless healing of infected wound

Abstract

Complex pathological microenvironment mainly characterized by excessive inflammation, reactive oxygen species (ROS) production, drug-resistant bacterial infection makes wound rapid scarless healing still a major clinical challenge. Inspired by skin composed principally of collagen and mucopolysaccharides, an injectable nanocomposite hydrogel with immunoregulation, antioxidant and antibacterial activity based on allyl glycidyl ether grafted gelatin (Gel-AGE), cysteamine grafted hyaluronic acid (HA-CSA) and poly(protocatechualdehyde)-coated gallium doped bioactive glass (PPA@GaBG) nanoparticles, was designed for treatment of infected wound. The PPA@GaBG/Gel-AGE/HA-CSA (PGBGH) hydrogel can be rapidly formed via thiol-ene photo-click chemistry between Gel-AGE and HA-CSA. In PGBGH hydrogel, the presence of core-shell PPA@GaBG significantly enhanced the antioxidant ability of hydrogels and M2 polarization of macrophages, as well as improving mechanical and tissue adhesive properties of the hydrogels via the formation of Schiff base bonds between PPA and gelatin/skin tissue. Moreover, the PPA shell effectively inhibited the ion burst release of Ga³⁺ observed in GaBG/GH hydrogels, which improved the biocompatibility of the PGBGH hydrogel while maintaining excellent antibacterial activity. As a result of multiple functions of the PPA@GaBG, the PGBGH hydrogel promoted angiogenesis, granulation tissue formation and re-epithelialization with improved deposition ratio of collagen III/I, which achieved the rapid scarless healing of infected wound.