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

Jiang Wu; Anqi Chen; Yajiao Zhou; Sen Zheng; Yao Yang; Ying An; Ke Xu; Huacheng He; Jianming Kang; Jittima Amie Luckanagul; Ming Xian; Jian Xiao; Qian Wang

doi:10.1016/j.biomaterials.2019.119398

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

Biomaterials. 2019 Nov:222:119398. doi: 10.1016/j.biomaterials.2019.119398. Epub 2019 Aug 16.

Authors

Jiang Wu¹, Anqi Chen², Yajiao Zhou², Sen Zheng², Yao Yang³, Ying An², Ke Xu¹, Huacheng He⁴, Jianming Kang⁵, Jittima Amie Luckanagul⁶, Ming Xian⁷, Jian Xiao⁸, Qian Wang⁹

Affiliations

¹ School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang, 325027, PR China.
² School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
³ College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang, 325027, PR China.
⁴ College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang, 325027, PR China. Electronic address: [email protected].
⁵ Department of Chemistry, Washington State University, Pullman, WA, 99164, United States.
⁶ Research Unit for Plant-produced Pharmaceuticals and the Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phayathai Rd., Wangmai, Pathumwan, Bangkok, 10330, Thailand.
⁷ Department of Chemistry, Washington State University, Pullman, WA, 99164, United States. Electronic address: [email protected].
⁸ School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. Electronic address: [email protected].
⁹ Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, United States. Electronic address: [email protected].

PMID: 31487582
DOI: 10.1016/j.biomaterials.2019.119398

Abstract

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.

Keywords: Controlled release; HA hydrogels; Hydrogen sulfide; M2 macrophage; Wound healing; pH responsive.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blotting, Western
Flow Cytometry
Hydrogels / chemistry*
Hydrogen Sulfide / chemistry*
Macrophages / drug effects*
Macrophages / metabolism*
Mice
Mice, Inbred C57BL
RAW 264.7 Cells
Reverse Transcriptase Polymerase Chain Reaction
Wound Healing / drug effects

Substances

Hydrogels
Hydrogen Sulfide