Protein therapeutics have become increasingly popular for the treatment of a variety of diseases owing to their specificity to targets of interest. However, challenges associated with them have limited their use for a range of ailments, including the limited options available for local controlled delivery. To address this challenge, degradable hydrogel microparticles, or microgels, loaded with model biocargoes were created with tunable release profiles or triggered burst release using chemistries responsive to endogenous or exogeneous stimuli, respectively. Specifically, microfluidic flow-focusing was utilized to form homogenous microgels with different spontaneous click chemistries that afforded degradation either in response to redox environments for sustained cargo release or light for on-demand cargo release. The resulting microgels were an appropriate size to remain localized within tissues upon injection and were easily passed through a needle relevant for injection, providing means for localized delivery. Release of a model biopolymer was observed over the course of several weeks for redox-responsive formulations or triggered for immediate release from the light-responsive formulation. Overall, we demonstrate the ability of microgels to be formulated with different materials chemistries to achieve various therapeutic release modalities, providing new tools for creation of more complex protein release profiles to improve therapeutic regimens.

中文翻译：

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通过自发点击化学形成的微凝胶，利用微流体流动聚焦来响应内源或外源刺激而释放货物


蛋白质疗法由于其对感兴趣靶点的特异性而在治疗多种疾病中变得越来越受欢迎。然而，与它们相关的挑战限制了它们在一系列疾病中的使用，包括局部控制分娩的可用选择有限。为了应对这一挑战，使用对内源性或外源性刺激敏感的化学物质分别创建了负载有模型生物货物的可降解水凝胶微粒或微凝胶，其具有可调释放曲线或触发爆发释放。具体来说，利用微流体流动聚焦形成具有不同自发点击化学的均质微凝胶，这些微凝胶可以响应氧化还原环境以实现持续的货物释放或响应于光以实现按需的货物释放。所得的微凝胶具有适当的尺寸，可以在注射后保持局部在组织内，并且很容易穿过与注射相关的针，从而提供局部递送的手段。对于氧化还原响应制剂，在几周的过程中观察到模型生物聚合物的释放，或者触发光响应制剂的立即释放。总体而言，我们证明了微凝胶能够用不同的材料化学成分配制以实现各种治疗释放方式，从而为创建更复杂的蛋白质释放曲线以改善治疗方案提供新工具。