In situ assembly of fibrinogen/hyaluronic acid hydrogel via knob-hole interaction for 3D cellular engineering.

In situ assembly of fibrinogen/hyaluronic acid hydrogel via knob-hole interaction for 3D cellular engineering.
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通过旋钮孔相互作用原位组装纤维蛋白原/透明质酸水凝胶,用于 3D 细胞工程

DOI:
10.1016/j.bioactmat.2017.09.002
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发表时间:
2017-12
影响因子:
18.9
通讯作者:
Gao C
Gao C
中科院分区:
工程技术1区
文献类型:
--
作者:
Huang S;Wang C;Xu J;Ma L;Gao C

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基于透明质酸(HA)的水凝胶具有良好的生物相容性和生物降解性,在生物医学领域有着广泛的应用。然而,在水凝胶形成过程中使用引发剂或交联剂可能会导致细胞毒性,从而损害生物相容性。受纤维蛋白凝胶的交联机理启发,本研究基于纤维蛋白原与羟基磷灰石的球孔相互作用,通过原位超分子组装制备了一种新型的羟基磷灰石水凝胶(KNOB-g-HA)。通过Michael加成反应将纤维蛋白结节A的模拟多肽GPRPAAC偶联到HA上,合成了结节接枝HA。然后,将纤维蛋白原溶液与纤维蛋白原按节孔比1.2简单混合,制得半透明的纤维蛋白原/纤维蛋白g-HA水凝胶。对纤维蛋白原浓度为50、100和200 mg/mL的纤维蛋白原/纽结-g-HA水凝胶的流变行为进行了评价,发现在整个频率范围内,所有组的动态存储模数(G‘)都大于损耗模数(G“)。扫描电子显微镜结果表明,纤维蛋白原/Knob-g-HA水凝胶呈现出与纤维蛋白原/MA-HA水凝胶不同的非均相网状结构。相应地,纤维蛋白原/Knob-g-HA水凝胶组的溶胀率较高。最后,在293T细胞的包封性实验中,通过活/死染色和四甲基偶氮唑盐比色法证明了纤维蛋白原/纽结-g-HA水凝胶的细胞相容性。所有这些结果突出了纤维蛋白原/KNOB-g-HA水凝胶在3D细胞工程中的生物潜力。在纤维蛋白凝胶的启发下,通过“纽结”-“空穴”特异性相互作用,制备了纤维蛋白原/纽结-g-透明质酸水凝胶。在生理条件下,不添加酶或交联剂即可制得细胞相容性良好的水凝胶。“旋钮”-“空穴”的相互作用使其有可能以温和和快速的方式制备具有良好细胞相容性的水凝胶。
Hyaluronic acid (HA)-based hydrogels have applied widely for biomedical applications due to its biocompatibility and biodegradability. However, the use of initiators or crosslinkers during the hydrogel formation may cause cytotoxicity and thereby impair the biocompatibility. Inspired by the crosslinking mechanism of fibrin gel, a novel HA-based hydrogel was developed via the in situ supramolecular assembly based on knob-hole interactions between fibrinogen and knob-grafted HA (knob-g-HA) in this study. The knob-grafted HA was synthesized by coupling knob peptides (GPRPAAC, a mimic peptide of fibrin knob A) to HA via Michael addition. Then the translucent fibrinogen/knob-g-HA hydrogels were prepared by simply mixing the solutions of knob-g-HA and fibrinogen at the knob/hole ratio of 1.2. The rheological behaviors of the fibrinogen/knob-g-HA hydrogels with the fibrinogen concentrations of 50, 100 and 200 mg/mL were evaluated, and it was found that the dynamic storage moduli (G′) were higher than the loss moduli (G″) over the whole frequency range for all the groups. The SEM results showed that fibrinogen/knob-g-HA hydrogels presented the heterogeneous mesh-like structures which were different from the honeycomb-like structures of fibrinogen/MA-HA hydrogels. Correspondingly, a higher swelling ratio was obtained in the groups of fibrinogen/knob-g-HA hydrogel. Finally, the cytocompatibility of fibrinogen/knob-g-HA hydrogels was proved by live/dead stainings and MTT assays in the 293T cells encapsulation test. All these results highlight the biological potential of the fibrinogen/knob-g-HA hydrogels for 3D cellular engineering. Inspired by fibrin gel, a fibrinogen/knob-g-hyaluronic acid hydrogel was fabricated via “knob”-“hole” specific interaction. The hydrogel showing good cytocompatibility was prepared under physiological condition without adding enzyme or crosslinker. The “knob” - “hole” interaction gives it potential to prepare a hydrogel with good cytocompatibility in a mild and fast manner.
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