Journal
BIOMATERIALS
Volume 222, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.119398
Keywords
Hydrogen sulfide; HA hydrogels; Wound healing; pH responsive; M2 macrophage; Controlled release
Funding
- Zhejiang Provincial Natural Science Foundation of China [LGF19H180008]
- National Natural Science Funding of China [81701809, 81601615]
- Zhejiang Qianjiang Talent project [QJD1803015]
- Opening Project of Zhejiang Provincial Top Key Discipline of Pharmaceutical Sciences [YKFJ3-011]
- NSF
- SC EPSCoR/IDeA Program under NSF Award [OIA-1655740]
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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.
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