期刊
ACTA BIOMATERIALIA
卷 41, 期 -, 页码 210-223出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2016.05.039
关键词
Sericin; Injectable hydrogels; Myocardial infarction; Functional recovery
资金
- National Natural Science Foundation of China [81272559, 81441077]
- International Science and Technology Corporation Program of Chinese Ministry of Science and Technology [S2014ZR0340]
- Science and Technology Program of Chinese Ministry of Education [113044A]
- Junior Thousand Talents Program of China
- Frontier Exploration Program of Huazhong University of Science and Technology [2015TS153]
- Natural Science Foundation Program of Hubei Province [2015CFA049]
Acute myocardial infarction (MI) leads to morbidity and mortality due to cardiac dysfunction. Here we identify sericin, a silk-derived protein, as an injectable therapeutic biomaterial for the minimally invasive MI repair. For the first time, sericin prepared in the form of an injectable hydrogel has been utilized for cardiac tissue engineering and its therapeutical outcomes evaluated in a mouse MI model. The injection of this sericin hydrogel into MI area reduces scar formation and infarct size, increases wall thickness and neovascularization, and inhibits the MI-induced inflammatory responses and apoptosis, thereby leading to a significant functional improvement. The potential therapeutical mechanisms have been further analyzed in vitro. Our results indicate that sericin downregulates pro -inflammatory cytokines (TNF-ct and IL 18) and chemokine (CCL2) and reduces TNF-alpha expression by suppressing the TLR4-MAPK/NF-kB pathways. Moreover, sericin exhibits angiogenic activity by promoting migration and tubular formation of human umbilical vessel endothelial cells (HUVECs). Also, sericin stimulates VEGFa expression via activating ERK phosphorylation. Further, sericin protects endothelial cells and cardiomyocytes from apoptosis by inhibiting the activation of caspase 3. Together, these diverse biochemical activities of sericin protein lead to a significant recovery of cardiac function. This work represents the first study reporting sericin as an effective therapeutic biomaterial for ischemic myocardial repair in vivo.
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