Bifunctional Monolithic Affinity Hydrogels for Dual-Protein Delivery

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Abstract
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.