Contribution of αβ T cells to macrophage polarization and MSC recruitment and proliferation on titanium implants.

Avery, Derek; Morandini, Lais; Gabriec, Melissa; Sheakley, Luke; Peralta, Matthieu; Donahue, Henry J; Martin, Rebecca K; Olivares-Navarrete, Rene · Acta Biomater · 2023

basic_science · Level V

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Abstract

Physiochemical cues like topography and wettability can impact the inflammatory response and tissue integration after biomaterial implantation. T cells are essential for immunomodulation of innate immune cells and play an important role in the host response to biomaterial implantation. This study aimed to understand how CD4<sup>+</sup> and CD8<sup>+</sup> T cell subsets, members of the αβ T cell family, polarize in response to smooth, rough, or rough-hydrophilic titanium (Ti) implants and whether their presence modulates immune cell crosstalk and mesenchymal stem cell (MSC) recruitment following biomaterial implantation. Post-implantation in mice, we found that CD4<sup>+</sup> and CD8<sup>+</sup> T cell subsets polarized differentially in response to modified Ti surfaces. Additionally, mice lacking αβ T cells had significantly more pro-inflammatory macrophages, fewer anti-inflammatory macrophages, and reduced MSC recruitment in response to modified Ti post-implantation than αβ T cell -competent mice. Our results demonstrate that T cell activation plays a significant role during the inflammatory response to implanted biomaterials, contributing to macrophage polarization and MSC recruitment and proliferation, and the absence of αβ T cells compromises new bone formation at the implantation site. STATEMENT OF SIGNIFICANCE: T cells are essential for immunomodulation and play an important role in the host response to biomaterial implantation. Our results demonstrate that T cells actively participate during the inflammatory response to implanted biomaterials, controlling macrophage phenotype and recruitment of MSCs to the implantation site.

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