摘要
Meniscal injury presents a formidable challenge and often leads to functional impairment and osteoarthritic progression.Meniscus tissue engineering(MTE)is a promising solution,as conventional strategies for modu-lating local immune responses and generating a conducive microenvironment for effective tissue repair are lacking.Recently,magnesium-containing bioactive glass nanospheres(Mg-BGNs)have shown promise in tissue regeneration.However,few studies have explored the ability of Mg-BGNs to promote meniscal regeneration.First,we verified the anti-inflammatory and fibrochondrogenic abilities of Mg-BGNs in vitro.A comprehensive in vivo evaluation of a rabbit critical-size meniscectomy model revealed that Mg-BGNs have multiple effects on meniscal reconstruction and effectively promote fibrochondrogenesis,collagen deposition,and cartilage pro-tection.Multiomics analysis was subsequently performed to further explore the mechanism by which Mg-BGNs regulate the regenerative microenvironment.Mechanistically,Mg-BGNs first activate the TRPM7 ion channel through the PI3K/AKT signaling pathway to promote the cellular function of synovium-derived mesenchymal stem cells and then activate the PPARγ/NF-κB axis to modulate macrophage polarization and inflammatory reactions.We demonstrated that Mg^(2+)is critical for the crosstalk among biomaterials,immune cells,and effector cells in Mg-BGN-mediated tissue regeneration.This study provides a theoretical basis for the application of Mg-BGNs as nanomedicines to achieve in situ tissue regeneration in complex intrajoint pathological microenvironments.
基金
grants from Natural Science Foundation of China(82272481,323B2043).
