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Title: 0129 - Titanium Surfaces Alter Wnt Signaling in Macrophages

Authors:

Kelly Hotchkiss, Virginia Commonwealth University
Manotri Chaubal, Virginia Commonwealth University
Claire Reagan, Virginia Commonwealth University
Jefferson Overlin, Virginia Commonwealth University
Rene Olivares-Navarrete (Presenter)
Virginia Commonwealth University

Abstract:

Objectives: Innate immune cells, specifically macrophages, determine the fate of implanted synthetic biomaterials based on their initial interaction with the material surface and subsequent activation profile. Titanium (Ti) surface modifications modulate macrophage activation, with hydrophilic-surfaces promoting anti-inflammatory and hydrophobic supporting pro-inflammatory activation. Wnt signaling can promote or inhibit the inflammatory response. However, the role of Wnt signaling in biomaterial-induced macrophage activation is unknown. The goal of this study was to determine the role Wnt signaling on in vitro and in vivo macrophage activation in response to Ti.

Methods: Primary macrophages derived from C57BL/6 mice were cultured on tissue culture polystyrene (TCPS), rough-Ti (SLA), or high-energy/rough-Ti (modSLA). The role of surface characteristics on Wnt signaling regulation in macrophages was examined by qPCR using custom arrays. Then, the effects of Wnt ligands (WNT3A, WNT5A, WNT5B, WNT7A, and WNT11) on cytokine release was also evaluated. Finally, Wnt ligand expression in macrophages adhered to titanium implants in vivo was evaluated. N=6 samples/variable; ANOVA, Bonferroni, p<0.05.

Results: Hydrophilic surfaces increased secretion of anti-inflammatory interleukins and expression of Wnt1, Wnt4, Wnt5b, Wnt9a/b, Wnt11, and Wnt16. Hydrophobic PT or SLA increased pro-inflammatory cytokines and expression of Wnt2, Wnt5a, Wnt10b, Ctnnb1, and Dkk2. Treatment with exogenous WNT3A or WNT5A increased expression of Il1b, Il6, Tnf, and Nos2, while WNT5B, WNT7A, and WNT11 increased expression of Il10, Il13, Tgfb1, and Mrc1. Finally, magnetically sorted macrophages adhered to modSLA implants in vivo had higher Wnt1, Wnt2a, Wnt3a, Wnt4, and Wnt5b than SLA, which had high Wnt7a, Wnt8a/b.

Conclusions: These results highlight the importance of Wnt signaling in macrophage activation and the relevance of implant surface characteristics in modulating inflammatory cytokines and Wnt signaling in vitro and in vivo.

Disclosure Statement:
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE

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