Treated dentin matrix-based scaffolds carrying TGF-β1/BMP4 for functional bio-root regeneration

被引：18
作者：
Chen, Jie [1 ,2 ,3 ,4 ,5 ]
Liao, Lijun [1 ,2 ,3 ,4 ,5 ]
Lana, Tingting [1 ,2 ,3 ,4 ,5 ]
Zhang, Zhijun [1 ,2 ,3 ,4 ,5 ]
Gai, Kuo [1 ,2 ,3 ,4 ,5 ]
Huang, Yibing [1 ,2 ,3 ,4 ,5 ]
Chen, Jinlong [1 ,2 ,3 ,4 ,6 ]
Tian, Weidong [1 ,2 ,3 ,4 ,6 ]
Guo, Weihua [1 ,2 ,3 ,4 ,5 ]
机构：
[1] Sichuan Univ, West China Hosp Stomatol, Minist Educ, Engn Res Ctr Oral Translat Med, 14,3rd Sec,Ren Min Nan Rd, Chengdu 610041, Sichuan, Peoples R China
[2] Sichuan Univ, West China Hosp Stomatol, Natl Engn Lab Oral Regenerat Med, Chengdu 610041, Sichuan, Peoples R China
[3] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Sichuan, Peoples R China
[4] Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, Chengdu 610041, Sichuan, Peoples R China
[5] Sichuan Univ, West China Sch Stomatol, Dept Pediat Dent, 14,3rd Sec,Ren Min Nan Rd, Chengdu 610041, Peoples R China
[6] Sichuan Univ, West China Sch Stomatol, Dept Oral & Maxillofacial Surg, Chengdu, Peoples R China
来源：
APPLIED MATERIALS TODAY | 2020年 / 20卷
基金：
中国国家自然科学基金;
关键词：
Enthesis formation; Cervical soft seal; Treated dentin matrix; Dental follicle stem cell; Bio-root regeneration; TOOTH REGENERATION; SOFT-TISSUES; STEM-CELLS; TGF-BETA; BONE; COMBINATION; DIFFERENTIATION; MAINTENANCE; ATTACHMENT; PROTEINS;
D O I：
10.1016/j.apmt.2020.100742
中图分类号：
T [工业技术];
学科分类号：
08 ;
摘要：
Biomaterial scaffold-based bioengineered tooth root (bio-root) has been proven to be a prospective tool for the treatment of tooth loss. However, while emulating the mechanical integrity of native tooth root, the regenerated bio-root still has limited capacity to achieve long-term functional stability because of lacking the effective cervical seal. Enlightened by physiological cues from cervical seal development and recovery of native tooth, this study reports a bioinspired approach as incorporation of two pivotal odontogenic growth factors (TGF-beta 1 and BMP4) into biomaterial scaffold (treated dentin matrix, TDM) embodying a spatial interface gradient for functional enthesis formation to promote functional bio-root regeneration. The biological characteristics of dental follicle stem cells (DFSCs) induced by TGF beta 1/BMP4 were studied by relevant gene and protein expressions in vitro as well as ectopic subcutaneous transplantation and orthotopic jaw bone implantation in vivo. We further fabricated artificial crown-TDM/TGF beta 1/BMP4/DFSCs in beagle to verify the potential occlusional function of regenerated bio-root. Notably, TGF beta 1/BMP4 synergistically activated proliferation, migration and osteoinductivity related to the enthesis differentiation of DFSCs as increasing expressions of Periostin, BSP, OPN, ALP, Vinculin, and Paxillin and ascending numbers of migrated cells. The TDM/TGF beta 1/BMP4/DFSCs composites imparted the uniform and persistent inductive interface for neovascularization and canonical enthesis regeneration. During more than 5 months follow-up in beagle model, the effectively functional bio-roots were distinguished by outstanding biomechanical properties and healthy gingiva similar to native teeth. This notion of integrating TGF beta 1/BMP4 with TDM and DFSCs provides an alternative strategy for biomimetic bio-root regeneration and other interface tissue engineering. (c) 2020 Elsevier Ltd. All rights reserved.
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页数：16
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