软骨发生
间充质干细胞
细胞生物学
软骨
化学
再生(生物学)
钙粘蛋白
旁分泌信号
干细胞
细胞
生物
生物化学
解剖
受体
作者
Xueping Wang,Xingquan Xu,Yan Zhang,Xueying An,Xue Zhang,Guoqiang Chen,Qing Jiang,Jun Yang
标识
DOI:10.1002/adhm.202200246
摘要
Mesenchymal stem cell (MSC) aggregates incorporated with microparticles of functional materials have shown promising prospects in the field of cell therapy for cartilage repair. Given the importance of cadherins in modulating the stemness and chondrogenesis of MSCs, the use of transforming growth factor β1 (TGFβ1)-loaded poly (lactic-co-glycolic acid) (PLGA)-based composite microparticles inspired by duo cadherin (human E- and N-cadherin fusion proteins) to construct a bioartificial stem cell niche in engineered human MSC (hMSC) aggregates to promote chondrogenesis and cartilage regeneration is proposed. The hE/N-cadherin-functionalized PLGA/chitosan-heparin-TGFβ1 (Duo hE/N-cad@P/C-h-TGFβ1) microparticles spatiotemporally upregulates the endogenous E/N-cadherin expression of hMSC aggregates which further amplifies the chondrogenic differentiation and modulate paracrine and anti-inflammatory functions of hMSCs toward constructing a favorable microenvironment for chondrogenesis. The Duo hE/N-cad@P/C-h-TGFβ1 microparticles finely regulate the response of hMSCs to biochemical and mechanical signal stimuli in the microenvironment through the cadherin/catenin-Yes-associated protein signal transduction, which inhibits the hypertrophy of hMSC-derived chondrocytes. Furthermore, immunofluorescent and histological examinations show that the Duo hE/N-cad@P/C-h-TGFβ1 microparticles significantly improve regeneration of cartilage and subchondral bone in vivo. Together, the application of duo cadherin-functionalized microparticles is considered an innovative material-wise approach to exogenously activate hMSC aggregates for functional applications in regenerative medicine.
科研通智能强力驱动
Strongly Powered by AbleSci AI