雜志名稱：Bioactive Materials
影響因子：18.0
文章題目：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
作者單位：
新鄉(xiāng)醫(yī)學(xué)院第三附屬醫(yī)院
上海交通大學(xué)醫(yī)學(xué)院附屬第九人民醫(yī)院
重慶醫(yī)科大學(xué)第二附屬醫(yī)院
中國國家級組織工程中心
引用YOBIBIO產(chǎn)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.
半月板是一種新月形纖維軟骨組織，用于提供結(jié)構(gòu)一致性和吸收機(jī)械力。目前，材料引導(dǎo)再生醫(yī)學(xué)策略的發(fā)展已成為半月板治療的有前途的替代方案。然而，它往往呈現(xiàn)出更復(fù)雜的免疫炎癥反應(yīng)病理狀況，從而不可避免地造成惡劣的微環(huán)境，極度阻礙纖維軟骨再生。因此，迫切需要開發(fā)生物活性材料，以實(shí)現(xiàn)整個(gè)再生期的軟骨免疫調(diào)節(jié)。在這項(xiàng)研究中，我們開發(fā)了一種具有軟骨免疫微環(huán)境 （CIME） 的新型動(dòng)態(tài)共價(jià)雜交 （DCH） 水凝膠，以暫時(shí)調(diào)節(jié)半月板再生。通過結(jié)合動(dòng)態(tài)硼酸酯交聯(lián)和共價(jià)光聚合反應(yīng)，DCH 水凝膠在實(shí)際作中表現(xiàn)出良好的注射性、自修復(fù)性和組織粘附特性。此外，通過引入時(shí)間按需調(diào)控系統(tǒng)成功創(chuàng)建了 CIME：早期優(yōu)先釋放萘普生抗炎藥通過 PI3K/Akt/mTOR 信號通路調(diào)節(jié) M1/M2 巨噬細(xì)胞極化，而 TGFβ3/CTGF 生長因子按需釋放，促進(jìn)后期調(diào)控后微環(huán)境中干細(xì)胞的纖維軟骨形成分化。最后，體內(nèi)實(shí)驗(yàn)證明，基于我們建立的軟骨免疫調(diào)節(jié)策略，通過激活干細(xì)胞歸巢的內(nèi)源性修復(fù)，對兔半月板軟骨缺損的修復(fù)效果令人滿意。
