Mast Cells Contribute to the Immunomodulatory Effect of the Biomaterial Microenvironment in a Gender Specific Manner
AbstractRegulation of the immune response contributes to the severity and outcomes in various disease conditions. Bioactive immunomodulatory biomaterials have shown promise for influencing these responses to promote tissue repair and regeneration. In this study, we investigated the role of mast cells in the regulation of the immune response to biomaterial scaffolds. In mast cell-deficient mice, there was dysregulation of the expected M1 to M2 macrophage transition typically induced by the biomaterial scaffold. Polarization progression deviated in a gender specific manner with an early transition to an M2 profile in female mice, while the male response was unable to properly transition past a pro-inflammatory M1 state. Both were reversed with mast cell adoptive transfer. Further investigation of the later stage immune response in male mice determined a sustained pro-inflammatory gene expression profile in deficient mice consisting of members from the IL-1 cytokine family and related downstream pathways. As mast cells were mainly associated with detrimental pro-inflammatory outcomes for biomaterial scaffolds, these results demonstrate their contribution to induced immunomodulatory therapies and support their potential as a critical immune regulatory element that can be manipulated for stimulating endogenous tissue repair.