期刊
MATERIALS TODAY BIO
卷 13, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.mtbio.2021.100195
关键词
Thermo-sensitive hydrogels; Small intestinal submucosa; Bone regeneration; Exosomes; Mechanical properties; Fusion peptides
资金
- National Natural Science Foundation of China (NSFC) [81701019]
- China Postdoctoral Science Foundation [2020M680253]
- Scientific Foundation of Tianjin Education Commission [2019KJ173]
- Science and technology project of Tianjin Health Committee [QN20026]
- Scientific research foundation of Stomatological Hospital of Tianjin Medical University [2020YKY06]
- Guangdong Basic and Applied Basic Research Foundation [2020A1515111182]
The mechanical properties of SIS hydrogels improved with the addition of 3-(3,4-dihydroxyphenyl) propionic acid (CA), while fusion peptides were designed to enhance the positive effects of exosomes on osteogenic differentiation of BMSCs. The combination of exosomes, fusion peptides, and SIS hydrogels showed enhanced retention and stability at the defect site in treating rat skull defect models.
Injectable thermo-sensitive hydrogels composed of small intestinal submucosa (SIS) with exosomes derived from bone marrow mesenchymal stem cells (BMSCs) are desired for bone regeneration. However, poor mechanical properties limit the clinical application of SIS hydrogels. Herein, the mechanical properties of SIS hydrogels incorporated with 3-(3,4-dihydroxyphenyl) propionic acid (CA) are assessed. The results show that the mechanical properties of SIS hydrogels are improved. In addition, the retention and stability of exosomes over time at the defect site are also challenges. Fusion peptides are designed by connecting collagen-binding domines (CBDs) of collagen type I/III with exosomal capture peptides CP05 (CRHSQMTVTSRL) directly or via rigid linkers (EAAAK). In vitro experiments demonstrate that fusion peptides are contribute to promoting the positive effect of exosomes on osteogenic differentiation of BMSCs. Meanwhile, the results of hydrogels combining exosomes and fusion peptides in the treatment of rat skull defect models reveal that fusion peptides could enhance the retention and stability of exosomes, thereby strengthen the therapeutic effect for skull defects. Therefore, SIS hydrogels with CA modified by fusion peptides and exosomes appear to be a promising strategy in bone regenerative medicine.
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