Biodegradable and biocompatible synthetic saccharide-Peptide hydrogels for three-dimensional stem cell culture.

Biodegradable and biocompatible synthetic saccharide-Peptide hydrogels for three-dimensional stem cell culture.
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DOI:
10.1021/bm100980w
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发表时间:
2011-03-14
期刊:
影响因子:
6.2
通讯作者:
Guan, Zhibin
Guan, Zhibin
中科院分区:
化学2区
文献类型:
--
作者:
Chawla, Kanika;Yu, Ting-Bin;Liao, Sophia W.;Guan, Zhibin

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糖肽水凝胶是我们实验室开发的用于再生医学应用的新的合成细胞外基质。在这项工作中,我们扩展了我们以前报道的体系,并通过Michael-type加成应用于半胱氨酸(Cys)和乙烯基砜(VS)功能化糖肽聚合物的共聚,用于细胞的包裹和三维(3D)培养。具体地说,我们的目标是(1)开发一种新型的水凝胶平台,用于在三维环境中包裹和培养间充质干细胞(MSCs);(2)表征水凝胶的可调特性,特别是降解、力学和凝胶网络特性;(3)确定糖肽水凝胶材料与MSCs的生物相容性。水凝胶的力学性能可通过改变vs:cys比率(=0.5、1或2)以及交联组分的pH(6、7或8)来调节。在VS:CyS=1和pH=6或7时形成较硬的凝胶。在pH为8或Cys过多(VS:CyS=0.5)或VS(VS:CyS=2)时形成的凝胶明显较软。交联度和VS:CyS比例对VS:CyS凝胶的降解行为也有影响,交联度越高,凝胶的质量损失越快。环境扫描电子显微镜(ESEM)分析表明,所有水凝胶均为多孔凝胶网络。单层培养的MSCs在可溶性半胱氨酸或VS共聚物(0.1-5 mg/ml)作用下未表现出明显的细胞毒作用。此外,MSCs在体外3D培养长达14天,对细胞活力没有不良影响。综上所述,我们建立并表征了一种可调节的3D糖-肽杂化共聚物水凝胶平台,用于培养MSCs。未来的研究将集中在利用水凝胶系统来控制MSCs的分化。
Saccharide-peptide hydrogels have been developed in our laboratory as new synthetic extracellular matrices for regenerative medicine applications. In this work, we have expanded on our previously reported system and applied copolymerization of cysteine (Cys) and vinyl sulfone (VS)-functionalized saccharide-peptide polymers via Michael-type addition for encapsulation and three-dimensional (3D) culture of cells. Specifically, our aims were to (1) develop a novel hydrogel platform which could be applied for encapsulating and culturing mesenchymal stem cells (MSCs) in a 3D environment, (2) characterize the tunable properties of the hydrogel, specifically, degradation, mechanical, and gel network properties and (3) determine the biocompatibility of the saccharide-peptide hydrogel material with MSCs. Hydrogel mechanical properties were tunable by varying VS:Cys ratio (= 0.5, 1, or 2) as well as the pH (6, 7, or 8) of the cross-linking components. Stiffer gels were formed at VS:Cys = 1 and pH 6 or 7. Gels formed at pH 8 or with excess Cys (VS:Cys = 0.5) or VS (VS:Cys = 2) were significantly softer. Cross-linking pH and VS:Cys ratio also had an effect on the degradation behavior of the VS:Cys gels, with higher cross-linking pH resulting in an accelerated loss of mass. Based on Environmental Scanning Electron Microscopy (ESEM) analysis, all hydrogels appeared to be porous gel networks. MSCs cultured in monolayer and exposed to soluble Cys or VS copolymers (0.1–5 mg/ml) did not exhibit measurable cytotoxicity. In addition, MSCs were cultured in 3D for up to 14 days in vitro without deleterious effects on cell viability. In summary, we have established and characterized a tunable 3D saccharide-peptide hybrid copolymer hydrogel platform for culturing MSCs. Future studies will focus on utilizing the hydrogel system for controlling the differentiation of MSCs.
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