Time-responsive osteogenic niche of stem cells: A sequentially triggered, dual-peptide loaded, alginate hybrid system for promoting cell activity and osteo-differentiation

被引:77
作者
Luo, Zuyuan [1 ,2 ]
Zhang, Siqi [2 ]
Pan, Jijia [2 ]
Shi, Rui [1 ]
Liu, Hao [1 ]
Lyu, Yalin [3 ]
Han, Xiao [3 ]
Li, Yan [1 ]
Yang, Yue [4 ]
Xu, Zhixiu [5 ]
Sui, Yi [1 ]
Luo, En [6 ,7 ]
Zhang, Yuanyuan [8 ]
Wei, Shicheng [1 ,2 ]
机构
[1] Peking Univ, Sch & Hosp Stomatol, Cent Lab, Natl Engn Lab Digital & Mat Technol Stomatol, Beijing 100081, Peoples R China
[2] Peking Univ, Acad Adv Interdisciplinary Studies, Lab Biomat & Regenerat Med, Beijing 100871, Peoples R China
[3] Capital Med Univ, Beijing Anzhen Hosp, Dept Stomatol, Beijing 100029, Peoples R China
[4] Capital Med Univ, Xuanwu Hosp, Dept Stomatol, Beijing 100053, Peoples R China
[5] Peking Univ, Sch & Hosp Stomatol, Dept Oral Pathol, Beijing 100081, Peoples R China
[6] Sichuan Univ, West China Sch, Dept Oral & Maxillofacial Surg, Chengdu 610041, Sichuan, Peoples R China
[7] Sichuan Univ, Hosp Stomatol, Chengdu 610041, Sichuan, Peoples R China
[8] Wake Forest Sch Med, Wake Forest Inst Regenerat Med, Winston Salem, NC 27157 USA
关键词
Nanocarriers; Multi-drug delivery; Organoids; Injectable hydrogel; 3D cell culture; Stem cell niche; MESOPOROUS SILICA NANOPARTICLES; IN-VITRO; OSTEOBLASTIC DIFFERENTIATION; DESIGNING MATERIALS; MATRIX ELASTICITY; BONE-FORMATION; CROSS-LINKING; STROMAL CELLS; HYDROGELS; DELIVERY;
D O I
10.1016/j.biomaterials.2018.02.025
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The efficacy of stem cell-based bone tissue engineering has been hampered by cell death and limited fate control. A smart cell culture system with the capability of sequentially delivering multiple factors in specific growth stages, like the mechanism of the natural extracellular matrix modulating tissue formation, is attractive for enhancing cell activity and controlling cell fate. Here, a bone forming peptide-1 (BFP-1)-laden mesoporous silica nanoparticles (pep@MSNs) incorporated adhesion peptide, containing the arginine-glycine-aspartic acid (RGD) domain, modified alginate hydrogel (RA) system (pep@MSNs-RA) was developed to promote the activity and stimulate osteo-differentiation of human mesenchymal stem cells (hMSCs) in sequence. The survivability and proliferation of hMSCs were enhanced in the adhesion peptide modified hydrogel. Next, BFP-1 released from pep@MSNs induced hMSCs osteo-differentiation after the proliferation stage. Moreover, BFP-1 near the cells was self captured by the additional cell-peptide cross-linked networks formed by the ligands (RGD) binding to receptors on the cell surface, leading to long-term sustained osteo-stimulation of hMSCs. The results suggest that independent and sequential stimulation in proliferation and osteo-differentiation stages could synergistically enhance the survivability, expansion, and osteogenesis of hMSCs, as compared to stimulating alone or simultaneously. Overall, this study provided a new and valid strategy for stem cell expansion and osteo-differentiation in 2D or 3D culture systems, possessing potential applications in 3D bio-printing and tissue regeneration. (C) 2018 Elsevier Ltd. All rights reserved.
引用
收藏
页码:25 / 42
页数:18
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