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自交联智能透明质酸水凝胶作为用于细胞培养的可注射三维支架。

The self-crosslinking smart hyaluronic acid hydrogels as injectable three-dimensional scaffolds for cells culture.

作者信息

Bian Shaoquan, He Mengmeng, Sui Junhui, Cai Hanxu, Sun Yong, Liang Jie, Fan Yujiang, Zhang Xingdong

机构信息

National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China.

出版信息

Colloids Surf B Biointerfaces. 2016 Apr 1;140:392-402. doi: 10.1016/j.colsurfb.2016.01.008. Epub 2016 Jan 6.

Abstract

Although the disulfide bond crosslinked hyaluronic acid hydrogels have been reported by many research groups, the major researches were focused on effectively forming hydrogels. However, few researchers paid attention to the potential significance of controlling the hydrogel formation and degradation, improving biocompatibility, reducing the toxicity of exogenous and providing convenience to the clinical operations later on. In this research, the novel controllable self-crosslinking smart hydrogels with in-situ gelation property was prepared by a single component, the thiolated hyaluronic acid derivative (HA-SH), and applied as a three-dimensional scaffold to mimic native extracellular matrix (ECM) for the culture of fibroblasts cells (L929) and chondrocytes. A series of HA-SH hydrogels were prepared depending on different degrees of thiol substitution (ranging from 10 to 60%) and molecule weights of HA (0.1, 0.3 and 1.0 MDa). The gelation time, swelling property and smart degradation behavior of HA-SH hydrogel were evaluated. The results showed that the gelation and degradation time of hydrogels could be controlled by adjusting the component of HA-SH polymers. The storage modulus of HA-SH hydrogels obtained by dynamic modulus analysis (DMA) could be up to 44.6 kPa. In addition, HA-SH hydrogels were investigated as a three-dimensional scaffold for the culture of fibroblasts cells (L929) and chondrocytes cells in vitro and as an injectable hydrogel for delivering chondrocytes cells in vivo. These results illustrated that HA-SH hydrogels with controllable gelation process, intelligent degradation behavior, excellent biocompatibility and convenient operational characteristics supplied potential clinical application capacity for tissue engineering and regenerative medicine.

摘要

尽管许多研究小组都报道了二硫键交联的透明质酸水凝胶,但主要研究集中在有效形成水凝胶上。然而,很少有研究人员关注控制水凝胶形成和降解、提高生物相容性、降低外源性毒性以及为后续临床操作提供便利的潜在意义。在本研究中,通过单一组分硫醇化透明质酸衍生物(HA-SH)制备了具有原位凝胶化特性的新型可控自交联智能水凝胶,并将其作为三维支架来模拟天然细胞外基质(ECM),用于成纤维细胞(L929)和软骨细胞的培养。根据不同的硫醇取代度(范围为10%至60%)和HA的分子量(0.1、0.3和1.0 MDa)制备了一系列HA-SH水凝胶。评估了HA-SH水凝胶的凝胶化时间、溶胀特性和智能降解行为。结果表明,通过调节HA-SH聚合物的组成可以控制水凝胶的凝胶化和降解时间。通过动态模量分析(DMA)获得的HA-SH水凝胶的储能模量可达44.6 kPa。此外,研究了HA-SH水凝胶作为三维支架在体外培养成纤维细胞(L929)和软骨细胞,以及作为可注射水凝胶在体内递送软骨细胞。这些结果表明,具有可控凝胶化过程、智能降解行为、优异生物相容性和便捷操作特性的HA-SH水凝胶为组织工程和再生医学提供了潜在的临床应用能力。

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