Pro-Regenerative Glycopeptide Hydrogel Activates Type 2 Immune Response for Wound Healing via Macrophage-T Cell Crosstalk

被引：20

作者：

Wang, Jingrong ^{[1
]}

Liu, Xiang ^{[2
]}

Wang, Yaping ^{[3
]}

Zhang, Yushan ^{[1
]}

Gao, Rui ^{[1
]}

Gao, Yu ^{[1
]}

Kong, Pengxu ^{[4
]}

Huangfu, Yini ^{[2
]}

Zhang, Chuangnian ^{[1
]}

Feng, Zujian ^{[1
]}

Huang, Pingsheng ^{[1
]}

Yang, Pengxiang ^{[5
,6
]}

Wang, Weiwei ^{[1
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Biomed Engn, State Key Lab Adv Med Mat & Devices, Tianjin 300192, Peoples R China

[2] Tianjin Univ, Sch Chem Engn & Technol, Dept Polymer Sci & Engn, Key Lab Syst Bioengn,Minist Educ, Tianjin 300072, Peoples R China

[3] Zhengzhou Univ, Affiliated Hosp 1, Med 3D Printing Ctr, Zhengzhou 450000, Peoples R China

[4] Chinese Acad Med Sci & Peking Union Med Coll, Fuwai Hosp, Dept Struct Heart Dis, Beijing 100037, Peoples R China

[5] Nantong Univ, Key Lab Neuroregenerat Jiangsu, Nantong 226001, Peoples R China

[6] Nantong Univ, Coinnovat Ctr Neuroregenerat, Minist Educ, Nantong 226001, Peoples R China

来源：

ADVANCED FUNCTIONAL MATERIALS | 2024年 / 34卷 / 16期

关键词：

glycopeptide; immunomodulatory hydrogel; regenerative medicine; tissue engineering; wound healing; TISSUE-REPAIR; DIFFERENTIATION; MICROENVIRONMENT; TH2; POLARIZATION; INFLAMMATION; SCAFFOLDS; MATRIX; CANCER; BONE;

D O I：

10.1002/adfm.202307711

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Immunomodulatory biomaterials are increasingly used in regenerative medicine. Biomimetic glycopeptide hydrogel is found to accelerate cutaneous wound healing by inducing macrophage M2-type polarization, however, it is unclear whether this will possibly orchestrate a pro-regenerative T cell immunity. Here the aim of this study is to elucidate the reparative T-cell immune response in tissue regeneration by augmenting macrophage-T cell crosstalk with a novel immunomodulatory glycopeptide hydrogel (termed as GRKgel) self-assembled by mannose receptor-binding glucomannan (GM) chemically grafted with RADA16-conjugated T-cell epitope. The glycopeptide can be phagocytized and processed by macrophages, which then presents peptides to naive T cells and polarizes them into T helper 2 (TH2) cells through IL-4-dependent STAT6/GATA3 or c-Maf pathways. Strikingly, full-thickness skin wound repair in mice indicates a superior efficacy of GRKgel on restoring the pathological structure and hair follicle by provoking TH2 immune response, increasing the residence of M2 macrophages, as well as promoting angiogenesis at the local tissue environment. Furthermore, genomics results illustrates the role of GRKgel serving as an immunomodulatory niche, orchestrating immune cell crosstalk and promoting extracellular matrix (ECM) reconstruction. Collectively, this study highlights the significance of crosstalk between immune cells in evoking pro-healing T-cell immunity, providing a promising drug-/cytokine-free strategy for endogenous tissue regeneration. GRKgel self-assembled by mannose receptor-binding glucomannan (GM) chemically grafted with RADA16-conjugated T-cell epitope without the presence of cytokines, drugs, or stem cells, is a promising immunomodulatory niche to regulate type 2 immune response in tissue regeneration, by coordinating self-assembling T-cell epitope, macrophage-T cell crosstalk, TH2 differentiation, as well as enhanced macrophage M2 residency.image

引用

页数：16

共 64 条

[1] Biomaterials as Local Niches for Immunomodulation [J].