# Role of Wnt Signaling in Macrophage Response to Biomaterials

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $353,997

## Abstract

The immune system modulates the initial response to biomaterial implantation, but which biomaterial
characteristics control the inflammatory response is unknown. The long-term goal is to understand the
signaling pathways used by innate immune cells in biomaterial recognition and inflammatory processes that
lead to tissue healing and regeneration. The objective of this proposal is to determine the role of Wnt
signaling in the response to biomaterial surface characteristics, inflammatory response, and recruitment of
stem and immune cells. The central hypothesis is that macrophages regulate bone healing through autocrine
phenotype modulation and secretion of Wnt ligands into the injury microenvironment, modulating the
recruitment and activity of stem and immune cells. The rationale underlying this proposal is to identify key Wnt
proteins and signaling pathways that can be targeted to modulate and ameliorate the inflammatory process
that occurs after biomaterial implantation. The proposed work will also identify key physical and chemical
components of biomaterial surfaces that control macrophage activation and function. The central hypothesis
will be tested through three aims: 1) Establish the role of Wnt signaling in macrophage activation and
inflammatory response on clinically relevant implant materials; 2) Establish the autocrine and paracrine effect
of Wnt proteins in macrophage activation, macrophage/MSC crosstalk, and immune cell recruitment; 3)
Elucidate the mechanism of macrophage activation and Wnt secretion in response to biomaterial surface
properties. We will pursue these aims using a combination of in vitro and in vivo studies with conditional
transgenic knockouts of Wnt signaling pathways in macrophages. The study of Wnt signaling on macrophage
behavior and as an orchestrator of the inflammatory response is innovative and has not been explored in the
context of biomaterial implantation. The proposed work is significant because it will determine the role of Wnt
proteins and signaling in macrophage activation and the production of the inflammatory microenvironment. It is
also significant because it will provide scientific evidence of the importance of Wnt signaling on the
inflammatory milieu that can be translated in the long term into other areas such as chronic inflammatory
diseases and cancer. The proximate expected outcome of this work is the understanding of Wnt signaling in
macrophage activation and its contribution on the inflammatory and healing process in response to biomaterial
surface characteristics. Results form this proposal will have important immediate positive impact establishing
the role of Wnt signaling in macrophage activation and inflammatory response providing key targets for
modulation of this activation and inflammatory response.

## Key facts

- **NIH application ID:** 9948636
- **Project number:** 5R01DE028919-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Rene Olivares-Navarrete
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $353,997
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948636

## Citation

> US National Institutes of Health, RePORTER application 9948636, Role of Wnt Signaling in Macrophage Response to Biomaterials (5R01DE028919-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948636. Licensed CC0.

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