期刊
ACS APPLIED MATERIALS & INTERFACES
卷 9, 期 40, 页码 34674-34686出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.7b10184
关键词
cell sheets; bone marrow mesenchymal stem cell; Runx2; LRP5; beta-catenin; osseointegration
资金
- National Natural Science Foundation of China [81272157, 31470945]
- Health Department of Zhejiang Province Fund [2015KYA147, 2014KYA127]
The combination of bone marrow mesenchymal stem cell (BMSC) sheets and titanium implants (BMSC sheet-implant complexes) can accelerate osseointegration. However, methods of fabricating BMSC sheet-implant complexes are quite limited, and the survival of BMSC sheet-implant complexes is one of the key barriers. Here, we show that a light-controlled fabricating system can generate less injured BMSC sheet-implant complexes with improved viability and osteogenesis and that noninvasive monitoring of the viability of BMSC sheet-implant complexes using a lentiviral delivery system is. feasible. Enhanced green fluorescent protein- and luciferase-expressing BMSC sheets were used to track the viability of BMSC sheet-implant complexes in vivo. The experiments of micro-computed tomography analysis and hard tissue slices were performed to evaluate the osteogenic ability of BMSC sheet-implant complexes in vivo. The results showed that BMSC sheet-implant complexes survived for almost 1 month after implantation. Notably, BMSC sheet-implant complexes fabricated by the light-controlled fabricating system had upregulating expression levels of low-density lipoprotein-receptor-related protein 5 (LRP5), beta-catenin, and runt-related transcription factor 2 (Runx2) compared to the complexes fabricated by mechanical scraping. Furthermore, we found that Runx2 directly bound to the rat LRP5 promoter and the LRP5/beta-catenin/Runx2 regulatory loop contributed to the enhancement of the osseointegrating potentials. In this study, we successfully fabricated BMSC sheet implant complexes with improved viability and osteogenesis and established a feasible, noninvasive, and continuous method for tracking BMSC sheet -implant complexes in vivo. Our findings lay the foundation for the application of BMSC sheet-implant complexes in vivo and open new avenues for engineered BMSC sheet-implant complexes.
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