Title

Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates

UMMS Affiliation

Program in Molecular Medicine

Publication Date

2017-06-01

Document Type

Article

Disciplines

Biomaterials | Biomedical Devices and Instrumentation | Immunology and Infectious Disease | Medical Immunology

Abstract

Host recognition and immune-mediated foreign body response to biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not. Macrophages, via CXCL13, lead to downstream B cell recruitment, which further potentiated fibrosis, as confirmed by B cell knockout and CXCL13 neutralization. Interestingly, colony stimulating factor-1 receptor (CSF1R) is significantly increased following implantation of multiple biomaterial classes: ceramic, polymer and hydrogel. Its inhibition, like macrophage depletion, leads to complete loss of fibrosis, but spares other macrophage functions such as wound healing, reactive oxygen species production and phagocytosis. Our results indicate that targeting CSF1R may allow for a more selective method of fibrosis inhibition, and improve biomaterial biocompatibility without the need for broad immunosuppression.

Keywords

Immunotherapy, Implants, Systems biology, Translational research

DOI of Published Version

10.1038/nmat4866

Source

Nat Mater. 2017 Jun;16(6):671-680. doi: 10.1038/nmat4866. Epub 2017 Mar 20. Link to article on publisher's site

Journal/Book/Conference Title

Nature materials

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

28319612

Link to Full Text

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