S-protected thiolated hyaluronic acid: In-situ crosslinking hydrogels for 3D cell culture scaffold

S-protected thiolated hyaluronic acid: In-situ crosslinking hydrogels for 3D cell culture scaffold
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DOI:
10.1016/j.carbpol.2020.116092
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发表时间:
2020-06-01
影响因子:
11.2
通讯作者:
Bernkop-Schnuerch, Andreas
Bernkop-Schnuerch, Andreas
中科院分区:
化学1区
文献类型:
--
作者:
Asim, Mulazim Hussain;Silberhumer, Stefanie;Bernkop-Schnuerch, Andreas

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本研究的目的是合成S-保护的巯基化透明质酸(HA),并评价其作为三维细胞培养支架的潜力。通过将N-乙酰基-S-((34(2,5-二氧代吡咯烷-1-基)氧基)-3-氧代丙基)硫代)半胱氨酸酰肼配体共价连接至HA来合成S-保护的硫醇化HA。水凝胶的结构,溶胀行为和流变性能进行了表征。此外,通过Caco-2和NIH 3 T3细胞的细胞增殖研究来评估S保护的巯基化HA水凝胶作为组织工程支架的潜力。在添加N-乙酰半胱氨酸(NAC)后,其显示增强的内聚性。S-保护的巯基化HA水凝胶的动态粘度通过加入NAC增加至19.5倍,并且在与粘液混合后增加至10.1倍。此外,包封到水凝胶中的Caco-2和NIH 3 T3细胞在体外增殖。由于这种新型的S-保护的硫醇化HA对氧化稳定,并且当与内源性硫醇接触时由于二硫化物交联而形成高度内聚的凝胶,因此它是用于3D细胞培养支架的有前途的工具。
The purpose of this study was to synthesize S-protected thiolated hyaluronic acid (HA) and to evaluate its potential for 3D cell culture scaffold. S-protected thiolated HA was synthesized by the covalent attachment of N-acetyl-S-((34(2,5-dioxopyrrolidin-1-yl)oxy)-3-oxopropyl)thio)cysteine hydrazide ligand to the HA. Hydrogels were characterized for texture, swelling behavior and rheological properties. Furthermore, the potential of Sprotected thiolated HA hydrogels as a scaffold for tissue engineering was evaluated by cell proliferation studies with Caco-2 and NIH 3T3 cells. It showed enhanced cohesion upon addition of N-acetyl cysteine (NAC). Dynamic viscosity of S-protected thiolated HA hydrogel was increased up to 19.5-fold by addition of NAC and 10.1-fold after mixing with mucus. Furthermore, Caco-2 and NIH 3T3 cells encapsulated into hydrogels proliferated invitro. As this novel S-protected thiolated HA is stable towards oxidation and forms highly cohesive gels when getting into contact with endogenous thiols due to disulfide-crosslinking, it is a promising tool for 3D cell culture scaffold.