Hydrogels formed via free radical-mediated thiol-ene step-growth photopolymerization have been developed for a broad range of tissue engineering and regenerative medicine applications. While the crosslinking mechanism of thiol-ene hydrogels has been well-described, there has been only limited work exploring the physical differences among gels arising from variations in crosslinker properties. Here, we show that the character of linear polyethylene glycol (PEG) dithiols used to crosslink multi-arm polyethylene glycol norbornene (PEGNB) can be used as a facile strategy to tune hydrogel formation kinetics, and therefore the equilibrium hydrogel network architecture. Specifically, we report the dramatic effect of crosslinker length on PEGNB hydrogel formation kinetics and the formed hydrogel properties. It is shown that the hydrogel formation kinetics and formed hydrogel properties can be tuned by solely varying the crosslinker length. It was hypothesized that under identical reaction conditions, a more accessible 3.5 k PEG dithiol crosslinker would improve network ideality relative to a shorter 1.5 k crosslinker. Longer linkers consequently promote significantly more rapid macromer crosslinking and therefore gelation. Accelerated gel formation satisfies an urgent unmet need for rapid polymerization in droplet microfluidics. Using long linkers, we demonstrate the ability to photopolymerize PEGNB microgels under flow on a microfluidic chip, with reliable control over microgel size and shape in a high-throughput manner. To further validate the potential of this platform to produce novel, microstructured cell carrier vehicles, 3T3 fibroblasts were successfully encapsulated and cultured over 14 days with excellent cell viability. This study demonstrates that PEGNB hydrogel dynamics could be readily customized to fulfill a variety of needs in tissue engineering, controlled cell delivery, or drug release applications.

中文翻译：

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交联剂的长度决定了逐步生长的水凝胶网络的形成动力学，并允许快速的片上光封装。

通过自由基介导的硫醇-烯逐步生长光聚合反应形成的水凝胶已被开发用于广泛的组织工程和再生医学应用。尽管已经很好地描述了硫醇-烯水凝胶的交联机理，但是仅有有限的工作来探索由于交联剂性质的变化而引起的凝胶之间的物理差异。在这里，我们表明用于交联多臂聚乙二醇降冰片烯（PEGNB）的线性聚乙二醇（PEG）二硫醇的特性可以用作调节水凝胶形成动力学的简便策略，因此也可以用作平衡水凝胶网络体系结构。具体来说，我们报道了交联剂长度对PEGNB水凝胶形成动力学和所形成的水凝胶性质的巨大影响。结果表明，仅改变交联剂的长度就可以调节水凝胶的形成动力学和形成的水凝胶性能。假设在相同的反应条件下，相对于较短的1.5 k交联剂，更易获得的3.5 k PEG二硫醇交联剂将改善网络的理想性。因此，较长的连接基大大促进了大单体的快速交联，从而促进了凝胶化。加速的凝胶形成满足了液滴微流体中快速聚合的迫切需求。使用长连接头，我们证明了在微流控芯片上流动下光聚合PEGNB微凝胶的能力，并以高通量方式可靠地控制了微凝胶的大小和形状。为了进一步验证该平台在生产新型微结构细胞载体车辆方面的潜力，3T3成纤维细胞成功封装并培养14天，具有出色的细胞活力。这项研究表明，PEGNB水凝胶动力学可以轻松定制，以满足组织工程，受控细胞递送或药物释放应用中的各种需求。