1. Immunomodulatory contribution of mast cells to the regenerative biomaterial microenvironment.
- Author
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Karkanitsa, Maria, Ungerleider, Jessica, Zelus, Emma, Zhang, Yuxue, Kawakami, Yu, Kawakami, Yuko, Kawakami, Toshiaki, Wang, Raymond, Christman, Karen, and Mesfin, Joshua
- Abstract
Bioactive immunomodulatory biomaterials have shown promise for influencing the immune response to promote tissue repair and regeneration. Macrophages and T cells have been associated with this response; however, other immune cell types have been traditionally overlooked. In this study, we investigated the role of mast cells in the regulation of the immune response to decellularized biomaterial scaffolds using a subcutaneous implant model. 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 sex-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 adoptive mast cell transfer. Further investigation of the later-stage immune response in male mice determined a greater sustained pro-inflammatory gene expression profile, including the IL-1 cytokine family, IL-6, alarmins, and chemokines. These results highlight mast cells as another important cell type that influences the immune response to pro-regenerative biomaterials.
- Published
- 2023