Mai Yuening, Wang Honglei, Lu Jianyu, Shi Songsong, Cai Yixin, Zhang Wei, Xie Sujie, Huang Runzhi, Ji Shizhao, Qu Xue
Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China.
Department of Burn Surgery, Institute of Burns, Changhai hospital, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
Bioact Mater. 2025 Jul 5;52:878-895. doi: 10.1016/j.bioactmat.2025.06.007. eCollection 2025 Oct.
Dynamic hydrogels can regulate immune responses, but decoupling bond exchange kinetics from static mechanical properties remains challenging. Here, we present a catalyst-mediated strategy to independently tune hydrogel network dynamics without altering crosslinking density or stiffness. A reversible acylhydrazone-based hydrogel system was constructed using lysozyme and PEG, with 4-amino-DL-phenylalanine (4a-Phe) as a catalyst to modulate bond exchange rates. This strategy enables effective decoupling of hydrogel viscoelasticity, allowing precise modulation of stress relaxation rates (τ) from 50 to 15 min, while maintaining nearly identical storage moduli (G'). The impact of hydrogel network dynamics on macrophage behavior was systematically investigated. Hydrogels with enhanced network dynamics significantly activated the JAK/STAT signaling pathway, promoting macrophage M2 polarization. These immunomodulatory effects fostered a pro-regenerative microenvironment, enhancing granulation tissue formation, angiogenesis, and accelerating wound closure in a diabetic mouse model. These findings underscore the significant potential of dynamic hydrogels in materiobiology, offering a novel approach to bridging materials science with immunoregulatory regenerative medicine.
动态水凝胶可以调节免疫反应，但将键交换动力学与静态力学性能解耦仍然具有挑战性。在此，我们提出一种催化剂介导的策略，可在不改变交联密度或硬度的情况下独立调节水凝胶网络动力学。使用溶菌酶和聚乙二醇构建了一种基于可逆酰腙的水凝胶系统，以4-氨基-DL-苯丙氨酸（4a-Phe）作为催化剂来调节键交换速率。该策略能够有效解耦水凝胶的粘弹性，使应力松弛速率（τ）从50分钟精确调节至15分钟，同时保持几乎相同的储能模量（G'）。系统研究了水凝胶网络动力学对巨噬细胞行为的影响。网络动力学增强的水凝胶显著激活JAK/STAT信号通路，促进巨噬细胞M2极化。这些免疫调节作用促进了促再生微环境的形成，增强了肉芽组织形成、血管生成，并加速了糖尿病小鼠模型中的伤口愈合。这些发现强调了动态水凝胶在材料生物学中的巨大潜力，为将材料科学与免疫调节再生医学联系起来提供了一种新方法。
