Immune-Modulating Mucin Hydrogel Microdroplets for the Encapsulation of Cell and Microtissue

Abstract

Immune-modulating biomaterials used to encapsulate cells and microtissue transplants can be engineered to dampen the immune reaction and increase treatment efficacy. Mucin-derived materials have gained attention for their ability to modulate macrophage and dendritic cell activity, and to trigger mild foreign body response when implanted in vivo. In this study, the potential of mucin hydrogels (Muc-gels) as cell-encapsulating materials is investigated. When placed in contact with blood, Muc-gels trigger significantly lower complement activation, compared to clinical grade alginate hydrogels. Muc-gel is a size-selective barrier strongly hindering the diffusion of molecules with a hydrodynamic radius larger than 6 nm such as immunoglobulins. Muc-gels support the growth of MIN6m9 insulin-secreting cells into islet-like organoids and the survival of primary human pancreatic islets, which maintained glucose responsiveness. Muc-gels can be shaped into microdroplets in which MIN6m9 cells or cell aggregates can be encapsulated without loss of viability. Microdroplet encapsulation will allow transplants to be easily injected and improve their survival by favoring mass transport through the capsule. The combination of strong immune modulatory properties, appropriate selective barrier profile, biocompatibility for embedded cells Muc-gels of particular value for microencapsulating cells or microtissues for transplantation.