Thermosensitive injectable hydrogels have been used for the delivery of pharmacological and cellular therapies in a variety of soft tissue applications. A promising class of synthetic, injectable hydrogels based upon oligo(ethylene glycol) methacrylate (OEGMA) monomers has been previously reported, but these polymers lack reactive groups for covalent attachment of therapeutic molecules. In this work, thermosensitive, amine-reactive and amine-functionalized polymers were developed by incorporation of methacrylic acid N-hydroxysuccinimide ester or 2-aminoethyl methacrylate into OEGMA-based polymers. A model therapeutic peptide, bivalirudin, was conjugated to the amine-reactive hydrogel to investigate effects on the polymer thermosensitivity and gelation properties. The ability to tune the thermosensitivity of the polymer in order to compensate for peptide hydrophilicity and maintain gelation capability below physiological temperature was demonstrated. Cell encapsulation studies using an H9 T-cell line (CD4+) were conducted to evaluate feasibility of the hydrogel as a carrier for cellular therapies. Although this class of polymers is generally considered to be non-toxic, it was found that concentrations required for gelation were incompatible with cell survival. Investigation into the cause of cytotoxicity revealed that a hydrolysis byproduct, diethylene glycol monomethyl ether, is likely a contributing factor. While modifications to structure or composition will be required to enable viable cell encapsulation, the functionalized injectable hydrogel has the potential for controlled delivery of a wide range of drugs.

中文翻译：

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一种功能化的可注射水凝胶，具有可调的热敏性，可进行局部药物递送：物理和毒理学性质的合成与表征

热敏性可注射水凝胶已用于各种软组织应用中的药理和细胞疗法的递送。先前已经报道了一类有前途的合成的，可注射的基于低聚（乙二醇）甲基丙烯酸甲酯（OEGMA）单体的水凝胶，但是这些聚合物缺乏用于治疗性分子共价连接的反应性基团。在这项工作中，通过将甲基丙烯酸N-羟基琥珀酰亚胺酯或甲基丙烯酸2-氨基乙基酯掺入基于OEGMA的聚合物中，开发了热敏性，胺反应性和胺官能化聚合物。将模型治疗性肽Bivalirudin与胺反应性水凝胶偶联，以研究其对聚合物热敏性和胶凝特性的影响。证明了调节聚合物的热敏性以补偿肽的亲水性并在低于生理温度的条件下保持胶凝能力的能力。进行了使用H9 T细胞系（CD4 +）的细胞封装研究，以评估水凝胶作为细胞疗法载体的可行性。尽管通常认为这类聚合物是无毒的，但是发现凝胶化所需的浓度与细胞存活不相容。对细胞毒性原因的研究表明，水解副产物二甘醇单甲醚可能是一个促成因素。尽管将需要对结构或组成进行修改以实现可行的细胞封装，