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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
Open accessAbstract
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 (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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“Studies using immune cell knockouts in animal models have identified macrophages as the primary drivers of fibrous capsule formation 5 .”
From Soft tissue-mimicking hydrogel stiffness modulates polarisation of human monocyte-derived macrophages (2025) · cites this paper as [5]
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Cites
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- Med, I. Medical Devices and the Public’s Health: The FDA 510(k) Clearance Process at 35 Years 1–298 (National Academies, 2011).
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Advances in Biomaterials for Drug Delivery
Fenton, O. S., Olafson, K. N., Pillai, P. S., Mitchell, M. J., & Langer, R. (2018) · Advanced Materials · doi:10.1002/adma.201705328 · Cited by 890
Self-citationBiofabrication strategies for 3D in vitro models and regenerative medicine
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Biomaterials: Foreign Bodies or Tuners for the Immune Response?
Mariani, E., Lisignoli, G., Borzì, R. M., & Pulsatelli, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030636 · Cited by 706
Activating an adaptive immune response from a hydrogel scaffold imparts regenerative wound healing
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Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics
Carnicer-Lombarte, A., Chen, S.-T., Malliaras, G. G., & Barone, D. G. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.622524 · Cited by 454
“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 healin…”
Background
Metadata
- 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
- Venue
- Nature Materials
- Published
- 2017-03-20
- Volume
- 16
- Issue
- 6
- Pages
- 671-680
- ISSN
- 1476-1122 (ISSN-L)
- 1476-4660
- 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
- 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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