可注射酰腙键连接的 RAFT 聚合物水凝胶用于持续释放蛋白质和细胞包封。

Injectable Acylhydrazone-Linked RAFT Polymer Hydrogels for Sustained Protein Release and Cell Encapsulation.

机构信息

Department of Biomedical Engineering, Purdue School of Engineering & Technology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202, USA.

Department of Biology, Purdue School of Science, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202, USA.

出版信息

Adv Healthc Mater. 2022 Apr;11(7):e2101284. doi: 10.1002/adhm.202101284. Epub 2021 Oct 13.

Abstract

A new class of temperature responsive polymer, termed PADO, is synthesized by reversible addition-fragmentation chain-transfer polymerization. Synthesized from copolymerization of diacetone acrylamide (DAAM), di(ethylene glycol) ethyl ether acrylate, and oligo(ethylene glycol) methyl ether acrylate, PADO polymer phase separates at temperature above its lower critical solution temperature (36-42 °C) due to enhanced hydrophobic interactions between the short ethylene glycol side chains. Solution of PADO polymers exhibit injectable shear-thinning properties and reach sol-gel transition rapidly (<5 min) at 37 °C. When the ketone moieties on DAAM are linked by adipic acid dihydrazdie, PADO polymers form crosslinked and injectable acylhydrazone hydrogels, which are hydrolytically degradable at a mild acidic environment owing to the pH sensitive acylhydrazone bonds. The pH-responsive degradation kinetics can be controlled by tuning polymer contents and ketone/hydrazide ratio. Importantly, the injectable PADO hydrogels are highly cytocompatible and can be easily formulated for pH-responsive sustained protein delivery.

摘要

一种新型的温度响应性聚合物,称为 PADO,是通过可逆加成-断裂链转移聚合合成的。由二丙酮丙烯酰胺(DAAM)、二(乙二醇)乙基醚丙烯酸酯和聚(乙二醇)甲基醚丙烯酸酯共聚合成,PADO 聚合物在其低临界溶液温度(36-42°C)以上由于短乙二醇侧链之间增强的疏水相互作用而发生相分离。PADO 聚合物溶液表现出可注射的剪切变稀特性,并在 37°C 下迅速达到溶胶-凝胶转变(<5min)。当 DAAM 上的酮基通过己二酸二酰肼连接时,PADO 聚合物形成交联和可注射的酰腙水凝胶,由于 pH 敏感的酰腙键,在温和的酸性环境下水解可降解。通过调整聚合物含量和酮/酰肼比可以控制 pH 响应的降解动力学。重要的是,可注射的 PADO 水凝胶具有高度的细胞相容性,并且可以很容易地配制成用于 pH 响应的持续蛋白质输送。

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