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Design and synthesis of non-ionic copolypeptide hydrogels with reversible thermoresponsive and tunable physical properties

机译:具有可逆热响应性和可调物理特性的非离子共多肽水凝胶的设计与合成

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摘要

Polypeptide based formulations that undergo liquid to hydrogel transitions upon change in temperature have become desirable targets since they can be mixed with cells or injected into tissues as liquids, and subsequently transform into rigid scaffolds or depots. Such materials have been challenging to prepare using synthetic polypeptides, especially when reversible gelation and tunable physical properties are desired. Here, we designed and prepared new non-ionic diblock copolypeptide hydrogels (DCH) named DCHEO, and also further incorporated copolypeptide domains into DCHEO to yield unprecedented thermoresponsive DCH, named DCHT. Although previous attempts to prepare non-ionic hydrogels composed solely of synthetic polypeptides have been unsuccessful, our designs yielded materials with highly reversible thermal transitions and tunable properties. Non-ionic, thermoresponsive DCHT were found to support the viability of suspended mesenchymal stem cells in vitro, and were able to dissolve and provide prolonged release of both hydrophilic and hydrophobic molecules. The versatility of these materials was further demonstrated by the independent molecular tuning of DCHT liquid viscosity at room temperature, DCHT hydrogel stiffness at elevated temperature, as well as the DCHT liquid to hydrogel transition temperature itself.
机译:在温度变化时经历液体到水凝胶转变的基于多肽的制剂已成为理想的目标,因为它们可以与细胞混合或以液体形式注射到组织中,然后转化为刚性支架或长效制剂。使用合成多肽制备此类材料一直具有挑战性,尤其是在需要可逆凝胶化和可调物理特性时。在这里,我们设计并制备了名为DCHEO的新型非离子二嵌段共多肽水凝胶(DCH),并将共多肽结构域进一步掺入DCHEO中以产生前所未有的热响应DCH,即DCHT。尽管以前尝试制备仅由合成多肽组成的非离子水凝胶的尝试均未成功,但我们的设计还是获得了具有高度可逆的热转变和可调性质的材料。发现非离子型,热响应性DCHT可在体外支持悬浮的间充质干细胞的活力,并能够溶解并延长亲水性和疏水性分子的释放。这些材料的多功能性进一步通过室温下DCHT液体粘度的分子调节,高温下DCHT水凝胶的刚度以及DCHT液体到水凝胶的转变温度本身的独立分子调节而得到进一步证明。

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