biostudies-literatureDoloff JCNIBIB NIH HHSNIDCR NIH HHSNIDDK NIH HHSNCI NIH HHS671-680https://www.ebi.ac.uk/biostudies/studies/S-EPMC5445003biostudies-literatureUnknown16(6)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.Nature materialsColony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates.PMC5445003U54 CA151884R37 EB000244P30 CA014051R01 EB000244UC4 DK104218R01 DE013023R01 EB000351R01 DK091526Tam HHQi MLangan EMa MSiebert SLanger RGreiner DLDoloff JCTang KSadraei AVegas AJGriffin MOberholzer JVeiseh OBader AThakrar RLi JWebber MChen MChiu AAnderson DGDholokia NJhunjhunwala SAresta-Dasilva SFarah SfalseColony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates.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.2017-01-01T00:00:00Z2017 Jun2024-11-13T12:47:03.677Z2019-03-27T02:46:03ZS-EPMC54450032831961210.1038/nmat4866