Chang Zhanyu, Ran Xinyue, Chu Yaru, Li Bohui, Fan Zhenlin, Li Genke, Li Dan, Ren Wenjie, Hua Yujie, Zhou Guangdong
The Third Affiliated Hospital of Xinxiang Medical University, Institutes of Health Central Plain, Clinical Medical Center of Tissue Engineering and Regeneration, Xinxiang Medical University, Xinxiang, Henan, 453003, PR China.
Center for Joint Surgery, Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China.
Bioact Mater. 2025 Apr 3;50:14-29. doi: 10.1016/j.bioactmat.2025.03.026. eCollection 2025 Aug.
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 () hydrogel with cartilaginous immune microenvironment () to temporally regulate meniscus regeneration. By combining dynamic boronic ester crosslinking and covalent photopolymerization reactions, hydrogels exhibit favorable injectability, self-healing, and tissue adhesion properties for practical operation. Furthermore, 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, 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.
ACS Appl Mater Interfaces. 2019-10-22
Tissue Eng Part B Rev. 2025-6