CircAars-Engineered ADSCs Facilitate Maxillofacial Bone Defects Repair Via Synergistic Capability of Osteogenic Differentiation, Macrophage Polarization and Angiogenesis

被引:0
|
作者
He, Yi [1 ,2 ]
Lu, Yunyang [1 ,2 ]
Li, Runze [1 ,2 ]
Tang, Yuquan [1 ,2 ,3 ]
Du, Weidong [1 ,2 ]
Zhang, Lejia [1 ,2 ]
Wu, Jie [1 ,2 ]
Li, Kechen [1 ,2 ]
Zhuang, Weijie [1 ,2 ]
Lv, Shiyu [1 ,2 ]
Han, Yaoling [1 ,2 ]
Tao, Bailong [1 ,2 ,4 ]
Deng, Feilong [1 ,2 ]
Zhao, Wei [1 ,2 ]
Yu, Dongsheng [1 ,2 ]
机构
[1] Sun Yat Sen Univ, Hosp Stomatol, Inst Stomatol Res, Guanghua Sch Stomatol, Guangzhou 510080, Peoples R China
[2] Guangdong Prov Key Lab Stomatol, Guangzhou 510055, Peoples R China
[3] Guangzhou Liwan Dist Stomatol Hosp, Guangzhou 510080, Peoples R China
[4] Chongqing Med Univ, Affiliated Hosp 1, Lab Res Ctr, Chongqing 400016, Peoples R China
基金
中国国家自然科学基金;
关键词
circular RNA; maxillofacial defects; osteogenic differentiation; osteo-immune modulation; stem cells; MESENCHYMAL STEM-CELLS; GELATIN-METHACRYLOYL HYDROGELS; CONDITIONED MEDIUM; REGENERATION; EXOSOMES; INFLAMMATION; MECHANISMS; DELIVERY;
D O I
10.1002/adhm.202404501
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Adipose-derived stem cells (ADSCs) hold significant promise in bone tissue engineering due to their self-renewal capacity and easy accessibility. However, their limited osteogenic potential remains a critical challenge for clinical application in bone repair. Emerging evidence suggests that circular RNAs (circRNAs) play a key role in regulating stem cell fate and osteogenesis. Despite this, the specific mechanisms by which circRNAs influence ADSCs in the context of bone tissue engineering are largely unexplored. This study introduces a novel strategy utilizing circAars, a specific circRNA, to modify ADSCs, which are then incorporated into gelatin methacryloyl (GelMA) hydrogels for the repair of critical-sized maxillofacial bone defects. The findings reveal that circAars predominantly localizes in the cytoplasm of ADSCs, where it acts as a competitive sponge for miR-128-3p, enhancing the osteogenic differentiation and migration capabilities of ADSCs. Furthermore, circAars-engineered ADSCs facilitate macrophage polarization from the M1 to M2 phenotype and enhance endothelial cell (EC) angiogenic potential through a paracrine mechanism. Additionally, GelMA scaffolds loaded with circAars-engineered ADSCs accelerate the repair of critical-sized maxillofacial bone defects by synergistically promoting osteogenesis, macrophage M2 polarization, and angiogenesis. This approach offers a promising therapeutic strategy for the treatment of critical-sized maxillofacial defects.
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页数:18
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