Granular Biomaterials as Bioactive Sponges for the Sequestration and Release of Signaling Molecules.

Abstract

A major challenge for the regeneration of chronic wounds is an underlying dysregulation of signaling molecules, including inflammatory cytokines and growth factors. To address this, we propose to use granular biomaterials composed of jammed microgels, to enable the rapid uptake and delivery of biomolecules, and provide a strategy to locally sequester and release biomolecules. Sequestration assays on model biomolecules of different sizes demonstrated that granular hydrogels exhibit faster transport than comparable bulk hydrogels due to enhanced surface area and decreased diffusion lengths. To demonstrate the potential of modular granular hydrogels to modulate local biomolecule concentrations, we engineered microgel scaffolds that can simultaneously sequester excess pro-inflammatory factors and release pro-healing factors. To target specific biomolecules, microgels were functionalized with affinity ligands that bind either to interleukin 6 (IL-6) or to vascular endothelial growth factor A (VEGF-A). Finally, disparate microgels were combined into a single granular biomaterial for simultaneous sequestration of IL-6 and release of VEGF-A. Overall, we demonstrate the potential of modular granular hydrogels to locally tailor the relative concentrations of pro- and anti-inflammatory factors. This article is protected by copyright. All rights reserved.