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

The 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. In this manuscript, thiolation and covalent tethering of IL-33 to the surface of microporous annealed particle (MAP) scaffolds are described to create a bioactive implant (IL33-MAP) that modulates the host immune response. It is found that IL33-MAP scaffolds activate immune cells through the ST2 receptor and recruits type 2 immune cells, which do not hinder tissue-implant integration. image