Conjugation of IL‐33 to Microporous Annealed Particle Scaffolds Enhances Type 2‐Like Immune Responses In Vitro and In Vivo

Abstract

AbstractThe inflammatory foreign body response (FBR) is the main driver of biomaterial implant failure. Current strategies to mitigate the onset of a FBR include modification of the implant surface, release of anti‐inflammatory drugs, and cell‐scale implant porosity. The microporous annealed particle (MAP) scaffold platform is an injectable, porous biomaterial composed of individual microgels, which are annealed in situ to provide a structurally stable scaffold with cell‐scale microporosity. MAP scaffold does not induce a discernible foreign body response in vivo and, therefore, can be used a “blank canvas” for biomaterial‐mediated immunomodulation. Damage associated molecular patterns (DAMPs), such as IL‐33, are potent regulators of type 2 immunity that play an important role in tissue repair. In this manuscript, IL‐33 is conjugated to the microgel building‐blocks of MAP scaffold to generate a bioactive material (IL33‐MAP) capable of stimulating macrophages in vitro via a ST‐2 receptor dependent pathway and modulating immune cell recruitment to the implant site in vivo, which indicates an upregulation of a type 2‐like immune response and downregulation of a type 1‐like immune response.