Lin Chien-Chi, Metters Andrew T
Department of Bioengineering, Clemson University, Clemson, South Carolina 29634, USA.
Biomacromolecules. 2008 Mar;9(3):789-95. doi: 10.1021/bm700940w. Epub 2008 Feb 8.
Multiple-protein delivery has been proven to be a critical consideration for promoting tissue regeneration. Many polymeric composite biomaterials have been designed and used for modulating dual-protein delivery to enhance tissue regeneration in vitro or in vivo. However, the fabrication conditions and low water contents within the portions of these composite matrices that determine protein release rates are not optimal for maintaining the stability of encapsulated macromolecular therapeutics. In this proof-of-concept work, we aim to resolve this deficiency by single-step fabrication of affinity hydrogels capable of independently delivering two or more proteins. Selective protein-binding sites were incorporated into poly(ethylene glycol) hydrogels via copolymerization with glycidyl methacrylate-iminodiacetic acid (GMIDA) ligands to modulate release of two model proteins, lysozyme and hexahistidine tagged green fluorescent protein (hisGFP), via two distinct matrix-binding mechanisms, namely electrostatic interaction and metal-ion chelation. Differing from composite matrices for dual-protein delivery, the results reported herein indicate that injectable monolithic affinity hydrogels are capable of rapidly encapsulating multiple therapeutic agents under mild physiological conditions and independently controlling their localized delivery. Most importantly, these affinity hydrogels retain high water permeabilities throughout the entire device, characteristics that are necessary for maintaining the stability and viability of encapsulated proteins and cells.
多种蛋白质递送已被证明是促进组织再生的关键考量因素。许多聚合物复合生物材料已被设计并用于调节双蛋白递送，以在体外或体内增强组织再生。然而，这些复合基质中决定蛋白质释放速率的部分的制备条件和低含水量对于维持包封的大分子治疗剂的稳定性并非最佳。在这项概念验证工作中，我们旨在通过一步法制备能够独立递送两种或更多种蛋白质的亲和水凝胶来解决这一缺陷。通过与甲基丙烯酸缩水甘油酯-亚氨基二乙酸（GMIDA）配体共聚，将选择性蛋白质结合位点引入聚乙二醇水凝胶中，以通过两种不同的基质结合机制，即静电相互作用和金属离子螯合，调节两种模型蛋白质（溶菌酶和六组氨酸标记的绿色荧光蛋白（hisGFP））的释放。与用于双蛋白递送的复合基质不同，本文报道的结果表明，可注射的整体亲和水凝胶能够在温和的生理条件下快速包封多种治疗剂，并独立控制它们的局部递送。最重要的是，这些亲和水凝胶在整个装置中保持高水渗透性，这是维持包封的蛋白质和细胞的稳定性和活力所必需的特性。
