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

自愈水凝胶 材料科学 牙髓(牙) 生物相容性 牙髓干细胞 组织工程 生物医学工程 细胞包封 化学工程 化学 体外 牙科 高分子化学 生物化学 工程类 冶金 医学
作者
Bing Han,Chunling Cao,Aijing Wang,Yanran Zhao,Moran Jin,Yuhan Wang,Shuqin Chen,Min Yu,Zhenzhong Yang,Xiaozhong Qu,Xiaoyan Wang
出处
期刊:ACS Applied Materials & Interfaces [American Chemical Society]
卷期号:15 (6): 7821-7832 被引量:19
标识
DOI:10.1021/acsami.2c20848
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.
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