Peptide-Functionalized Affinity Hydrogels for Reducing Local Inflammatory Response

Cell delivery using poly(ethylene glycol) (PEG) hydrogels has great potentials in tissue engineering and regenerative medicine applications, including islet encapsulation and transplantation to treat type 1 diabetes. However, one critical limitation of current hydrogel encapsulation technique is that it cannot prevent the diffusion of small antigenic, chemotactic, and cytotoxic molecules. These small molecules may hinder the survival of encapsulated cells in a multifaceted way. Here, we describe the synthesis, characterization, and application of peptide-functionalized affinity hydrogels capable of sequestering a pro-inflammatory chemokine, monocyte chemotactic protein-1 (MCP-1), secreted by the encapsulated pancreatic β-cells. We first demonstrate that extending the affinity peptide sequence away from the crosslinking site enhances MCP-1 binding and decreases release in PEG hydrogels. We then show that the novel affinity hydrogels significantly reduce the release of MCP-1 secreted by encapsulated MIN6 β-cells and isolated mouse islets. This strategy may improve the survival of encapsulated β-cells due to decreased MCP-1 secretion and reduce local inflammatory response.