In Situ Gelation of P(NIPAM-HEMA) Microgel Dispersion and Its Applications as Injectable 3D Cell Scaffold

In Situ Gelation of P(NIPAM-HEMA) Microgel Dispersion and Its Applications as Injectable 3D Cell Scaffold
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P(NIPAM-HEMA) 微凝胶分散体的原位凝胶化及其作为可注射 3D 细胞支架的应用

DOI:
10.1021/bm900022m
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发表时间:
2009-06-01
期刊:
影响因子:
6.2
通讯作者:
Guan, Ying
Guan, Ying
中科院分区:
化学2区
文献类型:
--
作者:
Gan, Tiantian;Zhang, Yongjun;Guan, Ying

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在这项工作中,我们试图开发一种新的热凝胶可注射支架用于三维细胞培养。而不是使用线性,分支,或接枝大分子,热敏微凝胶颗粒或微球被用作构建宏观水凝胶支架的基石。为了证明这一概念,我们合成了热敏性聚(n -异丙基丙烯酰胺-co-2-甲基丙烯酸羟乙酯)(P(NIPAM-HEMA))微凝胶颗粒,其体积相变温度(VPTT)约为29℃。流变学测试表明,当加热到其体积相变温度(VPTT)以上时,浓P(NIPAM-HEMA)微凝胶分散体具有胶体稳定性,表明疏水相互作用本身不能诱导分散体的热凝胶化。然而,在低浓度的CaCl2存在下,随着引入额外的离子交联,微凝胶分散凝胶并形成宏观水凝胶。微凝胶分散体的凝胶温度随着离子强度的增加而降低。扫描电镜观察表明,所得的大块凝胶具有相互连接的多孔微观结构。293T细胞是一种人类细胞系,将其与微凝胶分散液在室温下简单混合并加热至37℃,将其包裹在水凝胶中。MTT(3-[4,5-二甲基噻唑-2-基]-3,5-二苯基溴化四氮唑)测定显示,细胞在3D支架内存活并增殖。
In this work we try to develop a new thermal gelling injectable scaffold for three-dimensional cell culture. Instead of using linear, branched, or grafted macromolecules, thermosensitive microgel particles or microspheres are used as building blocks for the construction of the macroscopic hydrogel scaffold. As a proof of concept, thermosensitive poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (P(NIPAM-HEMA)) microgel particles were synthesized, which present a volume phase transition temperature (VPTT) at about 29 degrees C. Rheological test shows that the concentrated P(NIPAM-HEMA) microgel dispersion is colloidally stable when heated above its VPTT, indicating hydrophobic interaction alone can not induce thermal gelation of the dispersion. In the presence of a low concentration of CaCl2, however, with the introduction of additional ionic cross-linking, the microgel dispersion gelates and forms macroscopic hydrogel. Gelation temperature of the microgel dispersion decreases with increasing ionic strength. SEM observation reveals that the resultant bulky gel has an interconnected porous microstructure. 293T cells, a human cell line, were encapsulated inside the hydrogel by simple mixing with the microgel dispersion at room temperature and heating to 37 degrees C. MTT (3-[4,5-dimethylthiazol-2-yl]-3,5-diphenyl tetrazolium bromide) assays reveal that the cells are viable and proliferate inside the 3D scaffold.