Hierarchically Injectable Hydrogel Sequentially Delivers AntagomiR‐467a‐3p‐Loaded and AntagomiR‐874‐5p‐Loaded Satellite‐Cell‐Targeting Bioengineered Extracellular Vesicles Attenuating Sarcopenia

Author:

Dai Hanhao1,Luo Jun2,Deng Lili3,Song Chao1,Deng Zhibo1,Wu Yijing1,Gu Song4,Xu Jie12ORCID

Affiliation:

1. Shengli Clinical Medical College of Fujian Medical University Fuzhou 350000 China

2. Department of Orthopedics Fujian Provincial Hospital Fujian Medical University Fuzhou 350000 China

3. State Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of Materials Science and Engineering Donghua University Shanghai 201620 China

4. Trauma Center Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai 201620 China

Abstract

AbstractSarcopenia is a geriatric disease characterized by reduced muscle function and mass. The capacity to self‐renew and myogenesis of satellite cells (SCs) declines with age, resulting in age‐related sarcopenia. MicroRNAs (miRNAs) can regulate the proliferation and myogenesis of SCs. In this study, it is identified that miR‐467a‐3p and miR‐874‐5p could respectively mediate the stemness and myogenesis of SCs by performing bioinformatics analysis. AntagomiR‐467a‐3p (ant‐467a) and antagomiR‐874‐5p (ant‐874) improve the stemness and myogenesis of SCs, respectively. SC‐targeting extracellular vesicles (EVs) are constructed by overexpressing TSG101 on the surface of EVs isolated from bone marrow mesenchymal stem cells. Ant‐467a loaded EVs (EVs‐467a) and ant‐874 loaded EVs (EVs‐874) are prepared by transferring ant‐467a and ant‐874 into SC‐targeting EVs. EVs‐467a and EVs‐874 are more effective than ant‐467a and ant‐874 in promoting the stemness and myogenesis of SCs. Sequentially intermuscular injection of EVs‐467a and EVs‐874 significantly improve sarcopenia in ovariectomy mice. The effects of multiple injections of EVs‐467a and EVs‐874 in the treatment of sarcopenia could be achieved by using a hierarchically injectable hydrogel to sustainedly release EVs‐467a and EVs‐874 in vivo. The findings provide an EV‐based SC‐targeting antagomiRNAs controlled release strategy as a novel therapy against sarcopenia.

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biomaterials

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