Human urine-derived stem cell exosomes delivered via injectable GelMA templated hydrogel accelerate bone regeneration

被引:65
作者
Lu, Wei [1 ,3 ]
Zeng, Min [1 ,3 ]
Liu, Wenbin [1 ,3 ]
Ma, Tianliang [1 ,3 ]
Fan, Xiaolei [4 ]
Li, Hui [2 ]
Wang, Yinan [1 ,3 ]
Wang, Haoyi [1 ,3 ]
Hu, Yihe [1 ,2 ]
Xie, Jie [1 ,2 ]
机构
[1] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Dept Orthoped Surg, Changsha, Peoples R China
[2] Zhejiang Univ, Affiliated Hosp 1, Dept Orthoped, Med Coll, Hangzhou, Peoples R China
[3] Hunan Engn Res Ctr Biomed Met & Ceram Implants, Changsha, Peoples R China
[4] Xi An Jiao Tong Univ, Honghui Hosp, Dept Orthoped, Xian, Peoples R China
基金
中国国家自然科学基金;
关键词
Bone regeneration; Exosomes; H-type vessels; GelMA; HAMA; EXTRACELLULAR VESICLES; EPITHELIAL-CELLS; GELATIN; CULTURE; DEFECTS; DESIGN;
D O I
10.1016/j.mtbio.2023.100569
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The key to critical bone regeneration in tissue engineering relies on an ideal bio-scaffold coated with a controlled release of growth factors. Gelatin methacrylate (GelMA) and Hyaluronic acid methacrylate (HAMA) have been a novel topic of interest in bone regeneration while introducing appropriate nano-hydroxyapatite (nHAP) to improve its mechanical properties. And the exosomes derived from human urine-derived stem cells (human USCEXOs) have also been reported to promote osteogenesis in tissue engineering. The present study aimed to design a new GelMA-HAMA/nHAP composite hydrogel as a drug delivery system. The USCEXOs were encapsulated and slow-released in the hydrogel for better osteogenesis. The characterization of the GelMA-based hydrogel showed excellent controlled release performance and appropriate mechanical properties. The in vitro studies showed that the USCEXOs/GelMA-HAMA/nHAP composite hydrogel could promote the osteogenesis of bone marrow mesenchymal stem cells (BMSCs) and the angiogenesis of endothelial progenitor cells (EPCs), respec-tively. Meanwhile, the in vivo results confirmed that this composite hydrogel could significantly promote the defect repair of cranial bone in the rat model. In addition, we also found that USCEXOs/GelMA-HAMA/nHAP composite hydrogel can promote the formation of H-type vessels in the bone regeneration area, enhancing the therapeutic effect. In conclusion, our findings suggested that this controllable and biocompatible USCEXOs/ GelMA-HAMA/nHAP composite hydrogel may effectively promote bone regeneration by coupling osteogenesis and angiogenesis.
引用
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页数:15
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