Aptamer-functionalized hydrogels promote bone healing by selectively recruiting endogenous bone marrow mesenchymal stem cells

被引:6
作者
Gong, Jiang-Shan [1 ,2 ]
Zhu, Guo-Qiang [1 ,2 ]
Zhang, Yu [1 ]
Chen, Bei [1 ]
Liu, Yi-Wei [1 ,2 ]
Li, Hong-Ming [1 ,2 ]
He, Ze-Hui [1 ,2 ]
Zou, Jing-Tao [1 ,2 ]
Qian, Yu-Xuan [1 ,2 ]
Zhu, Sheng [1 ,2 ]
Hu, Xin-Yue [1 ,2 ]
Rao, Shan-Shan [1 ,2 ,3 ]
Cao, Jia [1 ,2 ,3 ]
Xie, Hui [1 ,2 ,3 ]
Wang, Zhen-Xing [1 ,2 ,3 ]
Du, Wei [1 ,2 ,3 ,4 ]
机构
[1] Cent South Univ, Xiangya Hosp, Movement Syst Injury & Repair Res Ctr, Dept Orthoped, Changsha 410008, Hunan, Peoples R China
[2] Hunan Key Lab Angmed, Changsha 410008, Hunan, Peoples R China
[3] Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China
[4] Cent South Univ, Xiangya Hosp, Dept Rehabil Med, Changsha 410008, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
Aptamer; Hydrogel; Fracture; Endogenous; Bone marrow mesenchymal stem cells; In situ regeneration; PEG;
D O I
10.1016/j.mtbio.2023.100854
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Bone regeneration heavily relies on bone marrow mesenchymal stem cells (BMSCs). However, recruiting endogenous BMSCs for in situ bone regeneration remains challenging. In this study, we developed a novel BMSC-aptamer (BMSC-apt) functionalized hydrogel (BMSC-aptgel) and evaluated its functions in recruiting BMSCs and promoting bone regeneration. The functional hydrogels were synthesized between maleimide-terminated 4-arm polyethylene glycols (PEG) and thiol-flanked PEG crosslinker, allowing rapid in situ gel formation. The aldehyde group-modified BMSC-apt was covalently bonded to a thiol-flanked PEG crosslinker to produce high-density aptamer coverage on the hydrogel surface. In vitro and in vivo studies demonstrated that the BMSC-aptgel significantly increased BMSC recruitment, migration, osteogenic differentiation, and biocompatibility. In vivo fluorescence tomography imaging demonstrated that functionalized hydrogels effectively recruited DiR-labeled BMSCs at the fracture site. Consequently, a mouse femur fracture model significantly enhanced new bone formation and mineralization. The aggregated BMSCs stimulated bone regeneration by balancing osteogenic and osteoclastic activities and reduced the local inflammatory response via paracrine effects. This study's findings suggest that the BMSC-aptgel can be a promising and effective strategy for promoting in situ bone regeneration.
引用
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页数:12
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