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

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 +17 more·2017·Nature Materials

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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  • CSF1 receptor has been recently identified as playing a unique role in FBR-associated inflammation, with its inhibition using both implant-encapsulated and systemically-delivered small molecule compounds leading to a decrease in macrophage activity and fibrosis around implanted materials without impacting wound healing.

    “CSF1 receptor has been recently identified as playing a unique role in FBR-associated inflammation, with its inhibition using both implant-encapsulated and systemically-delivered small molecule compounds leading to a decrease in macrophage activity and fibrosis around implanted materials without impacting wound healing (Doloff et al., 2017; Farah et al., 2019).”

    From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as Doloff et al., 2017

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  • Macrophages are the primary drivers of fibrous capsule formation in animal models.

    “Studies using immune cell knockouts in animal models have identified macrophages as the primary drivers of fibrous capsule formation 5 .”

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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.
Venue
Nature Materials
Published
2017-03-20
Volume
16
Issue
6
Pages
671-680
ISSN
  • 1476-1122 (ISSN-L)
  • 1476-4660
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
Open access
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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