Injectable Double-Network Hydrogel-Based Three-Dimensional Cell Culture Systems for Regenerating Dental Pulp

被引:31
作者
Han, Bing [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
Cao, Chunling [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
Wang, Aijing [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
Zhao, Yanran
Jin, Moran [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
Wang, Yuhan [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
Chen, Shuqin [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
Yu, Min [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
Yang, Zhenzhong [1 ,2 ,3 ,4 ,5 ,6 ,7 ,9 ]
Qu, Xiaozhong [1 ,2 ,3 ,4 ,5 ,6 ,7 ,8 ]
Wang, Xiaoyan [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
机构
[1] Peking Univ, Sch & Hosp Stomatol, Dept Cariol & Endodontol, Beijing 100049, Peoples R China
[2] Natl Ctr Stomatol, Beijing 100081, Peoples R China
[3] Natl Clin Res Ctr Oral Dis, Beijing 100081, Peoples R China
[4] Natl Engn Lab Digital & Mat Technol Stomatol, Beijing 100081, Peoples R China
[5] Beijing Key Lab Digital Stomatol, Beijing 100081, Peoples R China
[6] Minist Hlth, Res Ctr Engn & Technol Computerized Dent, Beijing 100081, Peoples R China
[7] NMPA Key Lab Dent Mat, Beijing 100081, Peoples R China
[8] Univ Chinese Acad Sci, Coll Mat Sci & Optoelect Technol, Beijing 100049, Peoples R China
[9] Tsinghua Univ, Dept Chem Engn, Beijing 100084, Peoples R China
基金
中国国家自然科学基金;
关键词
pulp regeneration; injectable hydrogel; double network; human dental pulp stem cells; matrix stiffness; ENDOTHELIAL-CELLS; STEM-CELLS; DIFFERENTIATION; STRATEGIES; TGF-BETA-1; STIFFNESS; CANCER; TOOTH;
D O I
10.1021/acsami.2c20848
中图分类号
TB3 [工程材料学];
学科分类号
082905 [生物质能源与材料];
摘要
The regeneration of dental pulp tissue is very important, but difficult, in dentistry. The biocompatibility, water content, and viscoelastic properties of pulp-like tissue must be optimized to achieve the efficient transfer of metabolites and nutrients, a suitable degradation rate, distribution of encapsulated cells, injectability, and gelation in situ under physiological conditions. As promising materials for pulp regeneration, hydrogel scaffolds have been produced to simulate the extracellular matrix and transmit signaling molecules. It is imperative to develop hydrogels to effectively regenerate pulp tissue for clinical application. Here, two injectable double-network (DN) hydrogel-based three-dimensional (3D) cell culture systems were developed for regenerating dental pulp. The microstructure, mechanical property, rheology property, and degradation behavior of the injectable DN glycol chitosan-based hydrogels in a simulated root canal model were characterized and compared to a single-network (SN) glycol chitosan-based hydrogel. Human dental pulp stem cells (hDPSCs) were then encapsulated into the GC-based hydrogels for the regeneration of pulp tissue, and the biological performance was investigated both in vitro and in vivo. The results showed that the DN hydrogels had ideal injectability under physiological conditions due to the dynamic nature of the crosslinks. Besides, the DN hydrogels exhibited better mechanical properties and longer degradation duration than the corresponding SN hydrogel. As a 3D cell culture system, the characteristics of the DN hydrogel facilitated odontogenic differentiation and mineralization of hDPSCs in vitro. Further in vivo analysis confirmed that the chemical composition, matrix stiffness, and degradation rate of the DN hydrogel matched those of pulp-like fibrous connective tissue, which might be related to Smad3 activation. These findings demonstrate that DN glycol chitosan-based hydrogels are suitable for the regeneration of pulp tissue.
引用
收藏
页码:7821 / 7832
页数:12
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