Acceleration of gelation in the biological environment and improvement of overall biological properties of a hydrogel is of enormous importance. Biopolymer stabilized gold (Au) nanoparticles (NPs) exhibit cytocompatibility and therapeutic activity. Hence, in situ gelation and subsequent improvement in the property of a hydrogel by employing Au NPs is an attractive approach. We report that stable Au NPs accelerate the conventional nucleophilic substitution reaction of activated halide-terminated poly(ethylene glycol) and tertiary amine functional macromolecules, leading to the rapid formation of injectable nanocomposite hydrogels in vivo and ex vivo with improved modulus, cell adhesion, cell proliferation, and cytocompatibility than that of a pristine hydrogel. NP surfaces with low chain grafting density and good colloidal stability are crucial requirements for the use of these NPs in the hydrogel formation. Influence of the structure of the amine functional prepolymer, the spacer connecting the halide leaving groups of the substrate, and the structure of the stabilizer on the rate promoting activity of the NPs have been evaluated with model low-molecular-weight substrates and macromolecules by ¹H NMR spectroscopy, rheological experiments, and density functional theory. Results indicate a significant effect of the spacer connecting the halide leaving group with the macromolecule. The Au nanocomposite hydrogels show sustained co-release of methotrexate, an anti-rheumatic drug, and the Au NPs. This work provides insights for designing an injectable nanocomposite hydrogel system with multifunctional property. The strategy of the use of cytocompatible Au NPs as a promoter provides new opportunity to obtain an injectable hydrogel system for biological applications.

中文翻译：

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金纳米颗粒促进可注射水凝胶的形成和生物学性质。

在生物环境中促进胶凝作用和改善水凝胶的整体生物学特性极为重要。生物聚合物稳定的金（Au）纳米颗粒（NPs）具有细胞相容性和治疗活性。因此，通过使用Au NPs原位凝胶化和随后改善水凝胶的性质是一种有吸引力的方法。我们报道稳定的金纳米粒子加速活化的卤化物封端的聚乙二醇和叔胺功能大分子的常规亲核取代反应，从而导致体内和离体可注射纳米复合水凝胶的快速形成，具有改善的模量，细胞粘附性，细胞与原始水凝胶相比，具有更高的增殖能力和细胞相容性。具有低链接枝密度和良好胶体稳定性的NP表面是在水凝胶形成过程中使用这些NP的关键要求。胺官能团预聚物的结构，连接底物的卤化物离去基团的间隔基和稳定剂的结构对NPs的速率促进活性的影响已通过模型低分子量底物和大分子通过以下方法进行了评估：¹ H NMR光谱，流变实验和密度泛函理论。结果表明间隔物将卤化物离去基团与大分子连接的显着效果。Au纳米复合水凝胶显示了抗风湿药甲氨蝶呤和Au NP的持续共释放。这项工作为设计具有多功能特性的可注射纳米复合水凝胶系统提供了见识。使用细胞相容性金纳米颗粒作为启动子的策略为获得用于生物应用的可注射水凝胶系统提供了新的机会。