Optimization of Interleukin-10 incorporation for dendritic cells embedded in Poly(ethylene glycol) hydrogels

Abstract

Translational research in biomaterials and immune engineering is leading to the development of novel advanced therapeutics to treat diseases such as cancer, autoimmunity, and viral infections. Dendritic cells (DCs) are at the center of these therapeutics given that they bridge innate and adaptive immunity. The biomaterial system developed herein uses a hydrogel carrier to deliver immunomodulatory DCs for amelioration of autoimmunity. This biomaterial vehicle is comprised of a poly (ethylene glycol)-4 arm maleimide (PEG-4MAL) hydrogels, conjugated with the immunosuppressive cytokine, interleukin10, IL-10, and cross-linked with a collagenase-degradable peptide sequence for the injectable delivery of immunosuppressive DCs to an anatomical disease-relevant site of the cervical lymph nodes, for intended application to treat multiple sclerosis. The amount of IL-10 incorporated in the hydrogel was optimized to be 500 ng in vitro, based on immunological endpoints. At this concentration, DCs exhibited the best viability, most immunosuppressive phenotype, and protection against proinflammatory insult as compared with hydrogel-incorporated DCs with lower IL-10 loading amounts. Additionally, the effect of the degradability of the PEG-4MAL hydrogel on the release rate of incorporated IL-10 was assessed by varying the ratio of degradable peptides: VPM (degradable) and DTT (nondegradable) and measuring the IL-10 release rates. This IL-10-conjugated hydrogel delivery system for immunosuppressive DCs is set to be assessed for in vivo functionality as the immunosuppressive cytokine provides a tolerogenic environment that keeps DCs in their immature phenotype, which consequently enhances cell viability and optimizes the system's immunomodulatory functionality.