Padmanabhan, Jagannath and Chen, Kellen and Sivaraj, Dharshan and Henn, Dominic and Kuehlmann, Britta A. and Kussie, Hudson C. and Zhao, Eric T. and Kahn, Anum and Bonham, Clark A. and Dohi, Teruyuki and Beck, Thomas C. and Trotsyuk, Artem A. and Stern-Buchbinder, Zachary A. and Than, Peter A. and Hosseini, Hadi S. and Barrera, Janos A. and Magbual, Noah J. and Leeolou, Melissa C. and Fischer, Katharina S. and Tigchelaar, Seth S. and Lin, John Q. and Perrault, David P. and Borrelli, Mimi R. and Kwon, Sun Hyung and Maan, Zeshaan N. and Dunn, James C. Y. and Nazerali, Rahim and Januszyk, Michael and Prantl, Lukas and Gurtner, Geoffrey C. (2023) Allometrically scaling tissue forces drive pathological foreign-body responses to implants via <i>Rac2</i>-activated myeloid cells. NATURE BIOMEDICAL ENGINEERING, 7. pp. 1419-1436. ISSN 2157-846X,
Full text not available from this repository. (Request a copy)Abstract
Small animals do not replicate the severity of the human foreign-body response (FBR) to implants. Here we show that the FBR can be driven by forces generated at the implant surface that, owing to allometric scaling, increase exponentially with body size. We found that the human FBR is mediated by immune-cell-specific RAC2 mechanotransduction signalling, independently of the chemistry and mechanical properties of the implant, and that a pathological FBR that is human-like at the molecular, cellular and tissue levels can be induced in mice via the application of human-tissue-scale forces through a vibrating silicone implant. FBRs to such elevated extrinsic forces in the mice were also mediated by the activation of Rac2 signalling in a subpopulation of mechanoresponsive myeloid cells, which could be substantially reduced via the pharmacological or genetic inhibition of Rac2. Our findings provide an explanation for the stark differences in FBRs observed in small animals and humans, and have implications for the design and safety of implantable devices.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PLASMINOGEN-ACTIVATOR; EXPRESSION; RECEPTOR; FIBROSIS; MECHANOTRANSDUCTION; INFLAMMATION; INHIBITOR; INTERFACE; REPAIR; ROLES |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Zentrum für Plastische-, Hand- und Wiederherstellungschirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Mar 2024 06:36 |
| Last Modified: | 20 Mar 2024 06:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60530 |
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