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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)671-680
Number of pages10
JournalNature Materials
Volume16
Issue number6
DOIs
StatePublished - Jun 1 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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