Conjugation of IL-33 to Microporous Annealed Particle Scaffolds Enhances Type 2-Like Immune Responses In Vitro and In Vivo
ADVANCED HEALTHCARE MATERIALS(2024)
摘要
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
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关键词
foreign body response,immunomodulation,porous biomaterials,tissue-implant integration
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