Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers

Haotian Bai; Noh Kyu-Cheol; Zhonghan Wang; Yutao Cui; He Liu; Hou Liu; Yubin Feng; Yue Zhao; Quan Lin; Zuhao Li

doi:10.1177/2041731420947242

Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers

J Tissue Eng. 2020 Jul 31:11:2041731420947242. doi: 10.1177/2041731420947242. eCollection 2020 Jan-Dec.

Authors

Haotian Bai¹, Noh Kyu-Cheol¹, Zhonghan Wang², Yutao Cui², He Liu², Hou Liu³, Yubin Feng³, Yue Zhao³, Quan Lin³, Zuhao Li^{2

4}

Affiliations

¹ Department of Orthopedics, Hallym University, Chuncheon, Gangwon-do, Korea.
² Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin, P. R. China.
³ State Key Lab of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, P. R. China.
⁴ Department of Pain, Renji Hospital, South Campus, Shanghai Jiaotong University, Shanghai, P. R. China.

Abstract

A diabetic foot ulcer (DFUs) is a state of prolonged chronic inflammation, which can result in amputation. Different from normal skin wounds, various commercially available dressings have not sufficiently improved the healing of DFUs. In this study, a novel self-healing hydrogel was prepared by in situ crosslinking of N-carboxyethyl chitosan (N-chitosan) and adipic acid dihydrazide (ADH) with hyaluronic acid-aldehyde (HA-ALD), to provide a moist and inflammatory relief environment to promote stem cell proliferation or secretion of growth factors, thus accelerating wound healing. The results demonstrated that this injectable and self-healing hydrogel has excellent swelling properties, stability, and mechanical properties. This biocompatible hydrogel stimulated secretion of growth factors from bone marrow mesenchymal stem cells (BM-MSCs) and regulated the inflammatory environment by inhibiting the expression of M1 macrophages and promoting the expression of M2 macrophages, resulting in granulation tissue formation, collagen deposition, nucleated cell proliferation, neovascularization, and enhanced diabetic wound healing. This study showed that N-chitosan/HA-ALD hydrogel could be used as a multifunctional injectable wound dressing to regulate chronic inflammation and provide an optimal environment for BM-MSCs to promote diabetic wound healing.

Keywords: BM-MSCs; Hydrogel; diabetic wound; inflammatory micro-environment.