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 prom-ising 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 carti-laginous 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 photo-polymerization 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.
基金
the National Key Research and Development Program of China(2024YFA1107800)
the Henan Provincial Science and Technology Research and Development Joint Fund(Industrial)(No.235101610001)
the Open Research Fund of Tissue Engineering and Regenerative Clinical Medical Center of Xin-xiang Medical University(No.2024SFYKFKT07)
the Key Research and Development and Promotion Special(Science and Technology)Project of Henan Province(No.242102310321)
National Natural Science Foundation of China(32430060,82472172,82402931,82102227)
Biomaterials and Regenerative Medicine Institute Cooperative Research Project of Shanghai Jiaotong University School of Medicine(2022LHA07)
Cross Research Fund Project of the Ninth People’s Hos-pital,Shanghai Jiaotong University School of Medicine(JYJC202302)
Shanghai Municipal Key Clinical Specialty(shslczdzk06601).
