Novel H2S-Releasing hydrogel for wound repair via in situ polarization of M2 macrophages

Hydrogen sulfide (H2S), as a gaseous messenger, exhibits potential therapeutic effects in biological and clinical applications. Herein, an in situ forming biomimetic hyaluronic acid (HA) hydrogel was used as a matrix to dope a pH-controllable H2S donor, JK1, to form a novel HA-JK1 hybrid system. This HA-JK1 hydrogel was designed as an ideal delivery scaffold for JK1 with pH-dependent prolonged H2S releasing profile. In vitro study suggested that JK1 could induce the polarization of M2 phenotype indicating a higher pro-healing efficiency of macrophages. The in vivo studies on dermal wounds showed that the HA-JK1 hybrid hydrogel significantly accelerated the wound regeneration process through enhanced re-epithelialization, collagen deposition, angiogenesis and cell proliferation. Furthermore, the in vivo results also demonstrated a higher level of M2 polarization in HA-JK1 treated group with reduced inflammation and improved wound remodeling effects, which was consistent with the in vitro results. These observations could be considered as a key to the efficient wound treatment. Therefore, we suggest that HA-JK1 can be used as a novel wound dressing material toward cutaneous wound model in vivo. This system should significantly enhance wound regeneration through the release of H2S that induces the expression of M2 macrophage phenotype.