For modulation of cellular behavior, systems that can provide controlled delivery of proteins (soluble signals) over a few hours to a few days are highly desirable. Conventional erosion-controlled systems are inadequate as their degradation spans days to months. Conversely, hydrogels offer quicker release but are limited by a high burst release that can lead to cytotoxicity and rapid depletion of the permeant. To avoid burst release and achieve controlled diffusion of proteins, we propose exploiting electrostatic interactions between the hydrogel matrix and proteins. Here we demonstrate this concept using two disparate hydrogel systems: (1) a chemically cross-linked protein (gelatin) matrix and (2) a physically cross-linked polysaccharide (agarose) matrix and three proteins having different isoelectric points. By introducing fixed charges into the hydrogel matrix using carboxylated agarose (CA), the precise and controlled release of BSA, lactoferrin, and FGF2 over a few hours to days is demonstrated. Using electroendosmosis, we further provide evidence for a clear role for CA in modulating the release. Our findings suggest that the paradigm presented herein has the potential to significantly enhance the design of hydrogel systems for the delivery of proteins and RNA therapeutics for vaccines and biomedical applications ranging from tissue engineering to functional coatings for medical devices.

中文翻译：

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调节水凝胶中蛋白质的短期递送


对于细胞行为的调节，非常需要能够在几小时到几天内提供蛋白质（可溶性信号）受控递送的系统。传统的侵蚀控制系统是不够的，因为它们的降解需要几天到几个月的时间。相反，水凝胶提供更快的释放，但受到高爆发释放的限制，这可能导致细胞毒性和渗透剂的快速消耗。为了避免爆发释放并实现蛋白质的受控扩散，我们建议利用水凝胶基质和蛋白质之间的静电相互作用。在这里，我们使用两个不同的水凝胶系统来演示这个概念：（1） 化学交联的蛋白质（明胶）基质和 （2） 物理交联的多糖（琼脂糖）基质和具有不同等电点的三种蛋白质。通过使用羧化琼脂糖 （CA） 将固定电荷引入水凝胶基质中，证明了 BSA、乳铁蛋白和 FGF2 在数小时到数天内的精确和受控释放。使用电内渗，我们进一步提供了 CA 在调节释放中明确作用的证据。我们的研究结果表明，本文提出的范式有可能显着增强水凝胶系统的设计，用于疫苗和生物医学应用的蛋白质和 RNA 治疗药物，从组织工程到医疗器械的功能涂层。