Extracellular Matrix-Mimetic Immunomodulatory Hydrogel for Accelerating Wound Healing

Honglei Wang; Runzhi Huang; Long Bai; Yixin Cai; Miao Lei; Chunyan Bao; Shaoliang Lin; Shizhao Ji; Changsheng Liu; Xue Qu

doi:10.1002/adhm.202301264

Extracellular Matrix-Mimetic Immunomodulatory Hydrogel for Accelerating Wound Healing

Adv Healthc Mater. 2023 Oct;12(27):e2301264. doi: 10.1002/adhm.202301264. Epub 2023 Jul 6.

Authors

Honglei Wang¹, Runzhi Huang², Long Bai³, Yixin Cai¹, Miao Lei¹, Chunyan Bao⁴, Shaoliang Lin¹, Shizhao Ji², Changsheng Liu¹, Xue Qu^{1

5

6}

Affiliations

¹ Key Laboratory for Ultrafine Materials of Ministry of Education, School of Material Science and Engineering, Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai, 200237, China.
² Department of Burn Surgery, Institute of Burns, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China.
³ Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
⁴ Key Laboratory for Advanced Materials, Institute of Fine Chemical School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, 200237, China.
⁵ Wenzhou Institute of Shanghai University, Wenzhou, 325000, China.
⁶ Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai, 200237, China.

PMID: 37341519
DOI: 10.1002/adhm.202301264

Abstract

Macrophages play a crucial role in the complete processes of tissue repair and regeneration, and the activation of M2 polarization is an effective approach to provide a pro-regenerative immune microenvironment. Natural extracellular matrix (ECM) has the capability to modulate macrophage activities via its molecular, physical, and mechanical properties. Inspired by this, an ECM-mimetic hydrogel strategy to modulate macrophages via its dynamic structural characteristics and bioactive cell adhesion sites is proposed. The LZM-SC/SS hydrogel is in situ formed through the amidation reaction between lysozyme (LZM), 4-arm-PEG-SC, and 4-arm-PEG-SS, where LZM provides DGR tripeptide for cell adhesion, 4-arm-PEG-SS provides succinyl ester for dynamic hydrolysis, and 4-arm-PEG-SC balances the stability and dynamics of the network. In vitro and subcutaneous tests indicate the dynamic structural evolution and cell adhesion capacity promotes macrophage movement and M2 polarization synergistically. Comprehensive bioinformatic analysis further confirms the immunomodulatory ability, and reveals a significant correlation between M2 polarization and cell adhesion. A full-thickness wound model is employed to validate the induced M2 polarization, vessel development, and accelerated healing by LZM-SC/SS. This study represents a pioneering exploration of macrophage modulation by biomaterials' structures and components rather than drug or cytokines and provides new strategies to promote tissue repair and regeneration.

Keywords: cell adhesion; dynamic hydrogels; immunomodulation; macrophage polarization; wound healing.

Publication types

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

MeSH terms

Biocompatible Materials / chemistry
Extracellular Matrix / chemistry
Hydrogels* / chemistry
Macrophages / metabolism
Wound Healing*

Substances

Hydrogels
Biocompatible Materials