Extracellular Matrix‐Mimetic Immunomodulatory Hydrogel for Accelerating Wound Healing
Extracellular Matrix‐Mimetic Immunomodulatory Hydrogel for Accelerating Wound Healing
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加速伤口愈合的细胞外基质模拟免疫调节水凝胶
DOI：
10.1002/adhm.202301264
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发表时间：
2023-06
影响因子：
10
通讯作者：
Honglei Wang;Runzhi Huang;L.J. Bai;Yixin Cai;Miao Lei;C. Bao;Shaoliang Lin;Shizhao Ji;
中科院分区：
文献类型：
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作者：
Honglei Wang;Runzhi Huang;L.J. Bai;Yixin Cai;Miao Lei;C. Bao;Shaoliang Lin;Shizhao Ji;
巨噬细胞在组织修复和再生的完整过程中起着至关重要的作用，M2极化的激活是提供促再生免疫微环境的有效方法。天然细胞外基质（ECM）具有通过其分子、物理和机械性质调节巨噬细胞活性的能力。受此启发，提出了一种ECM模拟水凝胶策略，通过其动态结构特征和生物活性细胞粘附位点来调节巨噬细胞。LZM-SC/SS水凝胶通过溶菌酶（LZM）、4-臂-PEG-SC和4-臂-PEG-SS之间的酰胺化反应原位形成，其中LZM提供用于细胞粘附的DGR三肽，4-臂-PEG-SS提供用于动态水解的琥珀酰酯，并且4-臂-PEG-SC平衡网络的稳定性和动力学。体外和皮下试验表明，动态结构演变和细胞粘附能力协同促进巨噬细胞运动和M2极化。综合生物信息学分析进一步证实了免疫调节能力，并揭示了M2极化与细胞粘附之间的显著相关性。采用全层伤口模型验证LZM-SC/SS的诱导M2极化、血管发育和加速愈合。这项研究代表了通过生物材料的结构和组分而不是药物或细胞因子调节巨噬细胞的开拓性探索，并为促进组织修复和再生提供了新的策略。
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.