Tetrakis(hydroxymethyl) phosphonium chloride as a covalent cross-linking agent for cell encapsulation within protein-based hydrogels.
Tetrakis(hydroxymethyl) phosphonium chloride as a covalent cross-linking agent for cell encapsulation within protein-based hydrogels.
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DOI：
10.1021/bm3015279
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发表时间：
2012-12-10
影响因子：
6.2
通讯作者：
Heilshorn, Sarah C.
中科院分区：
文献类型：
--
作者：
Chung, Cindy;Lampe, Kyle J.;Heilshorn, Sarah C.
天然组织为细胞提供复杂的三维 (3D) 环境，由细胞外基质蛋白和糖的水合网络组成。通过模拟天然组织的维度，同时解构环境参数的影响，基于蛋白质的水凝胶可以作为有吸引力的体外平台来研究细胞-基质相互作用。对于细胞封装，通过物理或共价交联形成水凝胶的过程必须温和且与细胞相容。虽然许多化学交联剂可用于水凝胶形成，但只有一小部分具有细胞相容性。因此，识别新的、可靠的细胞相容性交联剂可以为细胞封装应用的水凝胶设计提供更大的灵活性。在这里，我们引入四（羟甲基）氯化鏻 (THPC) 作为一种廉价的胺反应性水性交联剂，用于将 3D 细胞封装在基于蛋白质的水凝胶中。我们通过证明 THPC-胺反应与各种氨基酸的伯胺和仲胺反应的能力来表征 THPC-胺反应。此外，我们还证明了 THPC 通过重组类弹性蛋白调节水凝胶凝胶时间（6.7 ± 0.2 至 27 ± 1.2 分钟）和机械性能（储能模量 ~250 Pa 至 ~2200 Pa）的效用。最后，我们展示了 THPC 对两种细胞类型（胚胎干细胞和神经元细胞）的细胞相容性，其中细胞表现出在类弹性蛋白水凝胶中分化和/或生长的能力。
Native tissues provide cells with complex, three dimensional (3D) environments comprised of hydrated networks of extracellular matrix proteins and sugars. By mimicking the dimensionality of native tissue while deconstructing the effects of environmental parameters, protein-based hydrogels serve as attractive, in vitro platforms to investigate cell-matrix interactions. For cell encapsulation, the process of hydrogel formation through physical or covalent crosslinking must be mild and cell compatible. While many chemical crosslinkers are commercially available for hydrogel formation, only a subset are cytocompatible; therefore, the identification of new and reliable cytocompatible crosslinkers allows for greater flexibility of hydrogel design for cell encapsulation applications. Here, we introduce tetrakis (hydroxymethyl) phosphonium chloride (THPC) as an inexpensive, amine-reactive, aqueous crosslinker for 3D cell encapsulation in protein-based hydrogels. We characterize the THPC-amine reaction by demonstrating its ability to react with primary and secondary amines of various amino acids. In addition, we demonstrate the utility of THPC to tune hydrogel gelation time (6.7 ± 0.2 to 27 ± 1.2 min) and mechanical properties (storage moduli ~250 Pa to ~2200 Pa) with a recombinant elastin-like protein. Lastly, we show cytocompatibility of THPC for cell encapsulation of two cell types, embryonic stem cells and neuronal cells, where cells exhibited the ability to differentiate and/or grow in elastin-like protein hydrogels.
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影响因子：
3
作者：
Romano, Nicole H.;Sengupta, Debanti;Chung, Cindy;Heilshorn, Sarah C.
通讯作者：
Heilshorn, Sarah C.
影响因子：
37.8
作者：
Takahashi, T;Lord, B;Lee, RT
通讯作者：
Lee, RT
影响因子：
4.9
作者：
Lampe, Kyle J.;Mooney, Rachael G.;Mahoney, Melissa J.
通讯作者：
Mahoney, Melissa J.
影响因子：
3.8
作者：
Dang, SM;Kyba, M;Zandstra, PW
通讯作者：
Zandstra, PW
影响因子：
3.4
作者：
Straley, Karin S.;Heilshorn, Sarah C.
通讯作者：
Heilshorn, Sarah C.