Sprayable proteinic adhesive microgel-based immunosuppressive therapeutic coating for effective xenograft transplantation

Abstract

Tissue transplantation is an essential therapeutic approach for restoring function in patients with tissue damage caused by aging or accidents. However, immune rejection remains a significant challenge because the host immune system recognizes transplanted xenografts as foreign, triggering systemic inflammatory responses and graft failures. Although conventional oral or intravenous immunosuppressive therapies can mitigate immune rejection, they are often associated with severe systemic side effects and increased risk of infection. To address these challenges, a sprayable proteinic adhesive microgel (MG) coating system (Immune-shield) is developed using bioengineered mussel adhesive protein (MAP). Owing to its intrinsically disordered structure, MAPs exhibit low immune response, enabling localized and sustained delivery of immunosuppressive drugs. Immune-shield is directly applied to transplanted wet tissue surfaces using a simple spray and adheres strongly. It forms a stable coating that enables prolonged local retention and controlled release of cyclosporin A (CsA), a model immunosuppressive drug. In a rat skin xenograft model, Immune-shield effectively reduces inflammation and immune cell infiltration at the graft site, demonstrating effective local immunosuppressive efficacy without systemic drug administration. These results demonstrate the potential of sprayable, low-immunogenic protein-based adhesive MGs as a targeted immunosuppressive therapeutic platform for tissue and organ transplantation. © 2025 Elsevier B.V.