Allometrically scaling tissue forces drive pathological foreign-body responses to implants via Rac2-activated myeloid cells.

Autor: Padmanabhan J; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Chen K; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. kellenchen@arizona.edu.; Department of Surgery, University of Arizona College of Medicine, Tucson, AZ, USA. kellenchen@arizona.edu., Sivaraj D; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. ds311@stanford.edu.; Department of Surgery, University of Arizona College of Medicine, Tucson, AZ, USA. ds311@stanford.edu., Henn D; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.; Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA., Kuehlmann BA; Department of Plastic and Reconstructive Surgery, University Hospital Regensburg, Regensburg, Germany., Kussie HC; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.; Department of Surgery, University of Arizona College of Medicine, Tucson, AZ, USA., Zhao ET; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Kahn A; Cell Sciences Imaging Facility (CSIF), Beckman Center, Stanford University, Stanford, CA, USA., Bonham CA; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Dohi T; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Beck TC; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Trotsyuk AA; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.; Department of Surgery, University of Arizona College of Medicine, Tucson, AZ, USA., Stern-Buchbinder ZA; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Than PA; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Hosseini HS; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Barrera JA; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Magbual NJ; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Leeolou MC; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Fischer KS; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Tigchelaar SS; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Lin JQ; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Perrault DP; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Borrelli MR; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Kwon SH; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Maan ZN; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Dunn JCY; Division of Pediatric Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Nazerali R; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Januszyk M; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA., Prantl L; Department of Plastic and Reconstructive Surgery, University Hospital Regensburg, Regensburg, Germany., Gurtner GC; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. gurtner@surgery.arizona.edu.; Department of Surgery, University of Arizona College of Medicine, Tucson, AZ, USA. gurtner@surgery.arizona.edu.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2023 Nov; Vol. 7 (11), pp. 1419-1436. Date of Electronic Publication: 2023 Sep 25.
DOI: 10.1038/s41551-023-01091-5
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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