A common issue with hydrogel formulations is batch-to-batch irreproducibility originating from poorly defined polymer precursors. Here, we report the use of dendritic polymer end-groups to address this issue and maintain reproducibility between batches of poly(ethylene glycol) (PEG) hydrogels. Specifically, we synthesized two end-functionalized PEG chains: one with azide-terminated first- and second-generation dendrons and the other with strained cyclooctynes. The two complementary azide and alkyne polymers react via strain-promoted alkyne–azide cycloaddition (SPAAC) to produce hydrogels quickly in the absence of additional reagents or catalyst at low polymer concentrations. Hydrogels made with first-generation dendrons gelled in minutes and exhibited a small degree of swelling when incubated in PBS buffer at 37 °C, whereas hydrogels made from second-generation dendrons gelled in seconds with almost no swelling upon incubation at 37 °C. In both cases, the hydrogels proved reproducible, resulting in identical Young’s modulus values from different batches. The hydrogels prepared with second-generation dendrons were seeded with human mesenchymal stem cells and showed high cell viability as well as cell spreading over a two-week time frame. These studies show that the SPAAC hydrogels are noncytotoxic and are capable of supporting cell growth.

中文翻译：

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通过SPAAC交联可再生的Dendronized PEG水凝胶

水凝胶制剂的一个常见问题是批次间的不可重复性，其源自定义不明确的聚合物前体。在这里，我们报告使用树枝状聚合物端基来解决这个问题，并保持批次的聚（乙二醇）（PEG）水凝胶之间的可重复性。具体而言，我们合成了两条末端官能化的PEG链：一条带有叠氮化物封端的第一代和第二代树突，另一条带有应变的环辛炔。两种互补的叠氮化物和炔聚合物通过应变促进的炔-叠氮化物环加成反应（SPAAC）反应，在没有其他试剂或低聚合物浓度的催化剂的情况下，快速生成水凝胶。用第一代树突制成的水凝胶在数分钟内发生胶凝，并且在PBS缓冲液中于37°C孵育时表现出较小程度的溶胀，而由第二代树突制成的水凝胶在37°C孵育后几秒钟内凝胶化，几乎没有溶胀。在这两种情况下，水凝胶均具有可重现性，不同批次的杨氏模量值相同。用第二代树突制备的水凝胶接种了人间充质干细胞，在两周的时间内显示出高细胞活力以及细胞铺展性。这些研究表明，SPAAC水凝胶无细胞毒性，能够支持细胞生长。用第二代树突制备的水凝胶接种了人间充质干细胞，在两周的时间内显示出高细胞活力以及细胞铺展性。这些研究表明，SPAAC水凝胶无细胞毒性，能够支持细胞生长。用第二代树突制备的水凝胶接种了人间充质干细胞，在两周的时间内显示出高细胞活力以及细胞铺展性。这些研究表明，SPAAC水凝胶无细胞毒性，能够支持细胞生长。