Visible light cured thiol-vinyl hydrogels with tunable degradation for 3D cell culture.
Visible light cured thiol-vinyl hydrogels with tunable degradation for 3D cell culture.
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DOI：
10.1016/j.actbio.2013.08.044
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发表时间：
2014-01
影响因子：
9.7
通讯作者：
Lin, Chien-Chi
中科院分区：
文献类型：
--
作者：
Hao, Yiting;Shih, Han;Munoz, Zachary;Kemp, Arika;Lin, Chien-Chi
我们在这里报告了一种合成简单但高度可调和多样化的可见光介导的巯基乙烯基凝胶体系，用于制造细胞指导水凝胶。凝胶通过混合模式阶梯-链式生长光聚合实现，使用功能化的4臂聚乙二醇作为主链大分子，伊红- y作为光敏剂，含二硫醇分子作为双重用途的共引发剂/交联剂。用n -乙烯基吡咯烷酮（NVP）加速凝胶动力学和调节凝胶刚度。使用可见光（波长400-700nm）启动快速凝胶（凝胶点：~20秒），在几分钟内完成。当前的巯基-乙烯基凝胶化与先前可见光介导的光聚合的主要区别在于：(1)以前系统中使用的共引发剂三乙醇胺（TEOA）被多功能硫醇取代；(2)混合模式聚合的凝胶含有较少的网络非均质性。通过改变乙烯基和二巯基交联剂的性质，以及交联剂和NVP的浓度，可以调节聚乙二醇大聚物在相同浓度下的凝胶动力学和凝胶性能。具体来说，丙烯酸酯改性的PEG凝胶化速度最快，其次是丙烯酰胺和甲基丙烯酸酯功能化的PEG。NVP浓度的增加也会加速凝胶化，导致更高的网络交联密度。此外，凝胶配方中二硫醇肽浓度的增加增加了水凝胶的膨胀，降低了凝胶的硬度。由于在巯基-丙烯酸酯反应后形成巯基-醚-酯键，凝胶按照准一级降解动力学水解降解。通过调节聚合物前驱体溶液中硫醇或NVP的含量来控制降解速率。通过人间充质干细胞（hMSC）的原位包封，对该水凝胶体系的细胞相容性和实用性进行了评价。在整个研究过程中，包被的hMSCs仍然存活（约90%），并且通过控制凝胶降解的速率和方式，这些细胞可以不同程度地向成骨谱系分化。
We report here a synthetically simple yet highly tunable and diverse visible light mediated thiol-vinyl gelation system for fabricating cell-instructive hydrogels. Gelation was achieved via a mixed-mode step-and-chain-growth photopolymerization using functionalized 4-arm poly(ethylene glycol) as backbone macromer, eosin-Y as photosensitizer, and di-thiol containing molecule as dual purpose co-initiator/cross-linker. N-vinylpyrrolidone (NVP) was used to accelerate gelation kinetics and to adjust the stiffness of the hydrogels. Visible light (wavelength: 400–700nm) was used to initiate rapid gelation (gel points: ~20 seconds) that reached completion within a few minutes. The major differences between current thiol-vinyl gelation and prior visible light mediated photopolymerization are that: (1) the co-initiator triethanolamine (TEOA) used in the previous systems was replaced with multifunctional thiols and (2) mixed-mode polymerized gels contain less network heterogeneity. The gelation kinetics and gel properties at the same PEG macromer concentration could be tuned by changing the identity of vinyl groups and di-thiol cross-linkers, as well as concentration of cross-linker and NVP. Specifically, acrylate-modified PEG afforded the fastest gelation rate, followed by acrylamide and methacrylate-functionalized PEG. Increasing NVP concentration also accelerated gelation and led to a higher network cross-linking density. Further, increasing di-thiol peptide concentration in the gel formulation increased hydrogel swelling and decreased gel stiffness. Due to the formation of thiol-ether-ester bonds following thiol-acrylate reaction, the gels degraded hydrolytically following a pseudo first order degradation kinetics. Degradation rate was controlled by adjusting thiol or NVP content in the polymer precursor solution. The cytocompatibility and utility of this hydrogel system were evaluated using in situ encapsulation of human mesenchymal stem cells (hMSC). Encapsulated hMSCs remained alive (>90%) throughout the duration of the study and the cells were differentiated down osteogenic lineage with varying degrees by controlling the rate and mode of gel degradation.
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影响因子：
6.2
作者：
Lin, Chien-Chi;Anseth, Kristi S.
通讯作者：
Anseth, Kristi S.
影响因子：
14
作者：
Kizilel, S;Sawardecker, E;Pérez-Luna, VH
通讯作者：
Pérez-Luna, VH
影响因子：
41.2
作者：
Khetan S;Guvendiren M;Legant WR;Cohen DM;Chen CS;Burdick JA
通讯作者：
Burdick JA
影响因子：
6.2
作者：
Elbert, DL;Hubbell, JA
通讯作者：
Hubbell, JA
影响因子：
29.4
作者：
Fairbanks, Benjamin D;Schwartz, Michael P;Halevi, Alexandra E;Nuttelman, Charles R;Bowman, Christopher N;Anseth, Kristi S
通讯作者：
Anseth, Kristi S