Cited by 283Orthopaedic implants and arthroplastyTissue Engineering and Regenerative MedicineBone Tissue Engineering Materials

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

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Doloff, Joshua C., Veiseh, Omid, Vegas, Arturo J., Tam, Hok Hei, Farah, Shady, Ma, Minglin, Li, Jie, Bader, Andrew, Chiu, Alan, Sadraei, Atieh, Aresta-Dasilva, Stephanie, Griffin, Marissa, Jhunjhunwala, Siddharth, Webber, Matthew, Siebert, Sean, Tang, Katherine, Chen, Michael, Langan, Erin, Dholokia, Nimit, Thakrar, Raj, Qi, Meirigeng, Oberholzer, Jose, Greiner, Dale L., Langer, Robert, Anderson, Daniel G.·2017·Nature Materials

DOI 10.1038/nmat4866PMC PMC5445003

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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.

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Authors: Doloff, J. C., Veiseh, O., Vegas, A. J., Tam, H. H., Farah, S., Ma, M., Li, J., Bader, A., Chiu, A., Sadraei, A., Aresta-Dasilva, S., Griffin, M., Jhunjhunwala, S., Webber, M., Siebert, S., Tang, K., Chen, M., Langan, E., Dholokia, N., Thakrar, R., Qi, M., Oberholzer, J., Greiner, D. L., Langer, R., & Anderson, D. G.
Affiliations: Boston Children's Hospital (US)
Koch Institute for Integrative Cancer Research At MIT (US)
University of Illinois Chicago (US)
University of Massachusetts Chan Medical School (US)
Corresponding author: Anderson, Daniel G.
ORCID: Doloff, Joshua C.
Veiseh, Omid
Vegas, Arturo J.
Tam, Hok Hei
Farah, Shady
Ma, Minglin
Li, Jie
Sadraei, Atieh
Jhunjhunwala, Siddharth
Webber, Matthew
Tang, Katherine
Chen, Michael
Langan, Erin
Qi, Meirigeng
Greiner, Dale L.
Anderson, Daniel G.
Venue: Nature Materials
Publisher: Springer Science and Business Media LLC
Published: 2017-03-20
Volume: 16
Issue: 6
Pages: 671-680
ISSN: 1476-1122 (ISSN-L)
1476-4660
DOI: 10.1038/nmat4866
PMC: PMC5445003
OpenAlex: W2599718320
Cited by: 283
References: 50
Citations by year: 2026: 28 · 2025: 29 · 2024: 26 · 2023: 33 · 2022: 33 · 2021: 39 · 2020: 19 · 2019: 42 · 2018: 20 · 2017: 14
FWCI: 26.59
Type: journal article
Language: en
Update notices: correction (2021-05-19)
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Materials (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Funders: National Institutes of Health (4r37eb000244-34, 1uc4dk104218-01)
National Cancer Institute (U54CA151884, P30CA014051)
National Institute of Diabetes and Digestive and Kidney Diseases (UC4-DK-104218, U01DK104218, R01DK091526)
National Institute of Biomedical Imaging and Bioengineering (R01EB000244, R37-EB000244, R01EB000351)
National Institute of Dental and Craniofacial Research (R01DE013023)
Topics: Health Sciences › Medicine › Surgery › Orthopaedic implants and arthroplasty
Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
Keywords: colony-stimulating factor 1 receptor, foreign body reaction, implantable biomaterials, implant biocompatibility, macrophages, fibrosis, CXCL13, B cell recruitment, CSF1R inhibition, non-human primates, rodents, hydrogels, polymers, ceramics, innate and adaptive immunity
MeSH terms: Animals, Biocompatible Materials, Foreign-Body Reaction, Primates, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Prostheses and Implants, Mice

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

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