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Synthesis and fabrication of a degradable poly(N-isopropyl acrylamide) scaffold for tissue engineering applications

机译:用于组织工程应用的可降解聚(N-异丙基丙烯酰胺)支架的合成和制备

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摘要

Biodegradable poly(N-isopropyl acrylamide) (poly-NIPAM) hydrogels with controlled molecular weight of the parent polymer and its degradation products were synthesized by atom transfer radical polymerization in the presence of a polycaprolactone-based di-chlorinated macroinitiator and polycaprolactone dimethacrylate. The phase transition temperature, swelling, hydrolytic degradability, and mechanical properties at 25 and 37°C were explored. A cytocompatibility study showed good NIH3T3 cell response over 5 days culture on the surface of the hydrogels, demonstrated by a consistent increase in cell proliferation detected by an Alamar Blue assay. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo-lium bromide] results suggested that the hydrogels and their degradation products in the concentration range of 1–25 mg/ mL were not cytotoxic to NIH3T3 cells. A sphere-templating technique was utilized to fabricate biodegradable polyNIPAM scaffolds with monodisperse, pore size. Scaffolds with pore diameter of 48 ± 6 μm were loaded with A-10 smooth muscle cells and then warmed to 37°C entrapping cells in pores approximately 40 μm in diameter, a size we have found to be optimal for angiogenesis and biointegration. Due to their degradable nature, tunable molecular weight, highly interconnected morphology, thermally controlled monodisperse pore size, and temperature-induced volume expansion–contraction, the polyNIPAM-based scaffolds developed in this work will be valuable in tissue engineering.
机译:在基于聚己内酯的二氯化大分子引发剂和聚己内酯二甲基丙烯酸酯的存在下,通过原子转移自由基聚合合成了具有受控分子量的母体聚合物及其降解产物的可生物降解的聚(N-异丙基丙烯酰胺)(poly-NIPAM)水凝胶。探索了在25和37°C下的相变温度,溶胀,水解降解性和机械性能。细胞相容性研究显示,在水凝胶表面培养5天后,NIH3T3细胞反应良好,这通过Alamar Blue分析检测到的细胞增殖持续增加得以证明。 MTT [3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化铵]结果表明,浓度为1–25 mg / mL的水凝胶及其降解产物对NIH3T3没有细胞毒性细胞。利用球形模板技术来制造具有单分散性,孔径的可生物降解的polyNIPAM支架。将孔径为48±6μm的支架装载A-10平滑肌细胞,然后在直径约40μm的孔中加热到37°C的捕获细胞,我们发现该尺寸对于血管生成和生物整合是最佳的。由于其可降解的性质,可调节的分子量,高度相关的形态,热控制的单分散孔径以及温度引起的体积膨胀-收缩,这项工作开发的基于polyNIPAM的支架在组织工程中将具有重要价值。

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