杂志名称：Bioactive Materials
影响因子：18.0
文章题目：Dynamic-covalent hybrid hydrogels with cartilaginous immune microenvironment temporally regulating meniscus regeneration
DOI：https://doi.org/10.1016/j.bioactmat.2025.03.026
作者：Zhanyu Chang , Xinyue Ran , Yaru Chu , Bohui Li , Zhenlin Fan , Genke Li , Dan Li , Wenjie Ren , Yujie Hua , Guangdong Zhou
作者单位：
新乡医学院第三附属医院
上海交通大学医学院附属第九人民医院
重庆医科大学第二附属医院
中国国家级组织工程中心
引用YOBIBIO产品：
U96-2203E  Human TGFβ3 ELISA Kit
U96-1368E  Human CTGF ELISA kit

文章摘要：
Meniscus is a crescent-shaped fibrocartilage tissue for providing structural congruence and absorbing mechanical forces. Currently, the development of material-guided regeneration medicine strategy has emerged as a promising alternative for meniscus treatment. However, it often presents more complex pathological conditions of immune-inflammatory responses, and thus inevitably causes a harsh microenvironment that extremely hinders fibrocartilage regeneration. Therefore, there is an urgent need to develop bioactive materials to achieve cartilaginous immunomodulatory throughout the whole regenerative periods. In this study, we develop a novel dynamic-covalent hybrid (DCH) hydrogel with cartilaginous immune microenvironment (CIME) to temporally regulate meniscus regeneration. By combining dynamic boronic ester crosslinking and covalent photopolymerization reactions, DCH hydrogels exhibit favorable injectability, self-healing, and tissue adhesion properties for practical operation. Furthermore, CIME is successfully created by the introduction of a temporally on-demand regulatory system: naproxen anti-inflammatory drugs are preferentially released to regulate M1/M2 macrophage polarization through PI3K/Akt/mTOR signaling pathway at early stage, while TGFβ3/CTGF growth factors are on-demand released to promote fibrochondrogenic differentiation of stem cells in the post-regulatory microenvironment at later stage. Finally, in vivo experiments demonstrate the satisfactory repair of meniscus cartilage defects in rabbits by activating the endogenous repair of stem cells homing based on our established cartilaginous immunomodulatory strategy.

半月板是一种新月形纤维软骨组织，用于提供结构一致性和吸收机械力。目前，材料引导再生医学策略的发展已成为半月板治疗的有前途的替代方案。然而，它往往呈现出更复杂的免疫炎症反应病理状况，从而不可避免地造成恶劣的微环境，极度阻碍纤维软骨再生。因此，迫切需要开发生物活性材料，以实现整个再生期的软骨免疫调节。在这项研究中，我们开发了一种具有软骨免疫微环境 （CIME） 的新型动态共价杂交 （DCH） 水凝胶，以暂时调节半月板再生。通过结合动态硼酸酯交联和共价光聚合反应，DCH 水凝胶在实际作中表现出良好的注射性、自修复性和组织粘附特性。此外，通过引入时间按需调控系统成功创建了 CIME：早期优先释放萘普生抗炎药通过 PI3K/Akt/mTOR 信号通路调节 M1/M2 巨噬细胞极化，而 TGFβ3/CTGF 生长因子按需释放，促进后期调控后微环境中干细胞的纤维软骨形成分化。最后，体内实验证明，基于我们建立的软骨免疫调节策略，通过激活干细胞归巢的内源性修复，对兔半月板软骨缺损的修复效果令人满意。