Allometrically scaling tissue forces drive pathological foreign-body responses to implants via Rac2-activated myeloid cells.
Allometrically scaling tissue forces drive pathological foreign-body responses to implants via Rac2-activated myeloid cells.
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DOI：
10.1038/s41551-023-01091-5
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发表时间：
2023-11
影响因子：
28.1
通讯作者：
中科院分区：
文献类型：
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作者：
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. Elevated extrinsic tissue-scale forces can drive pathological foreign-body responses to implants, mediated by the Rac2-mediated activation of a subpopulation of mechanoresponsive myeloid cells.
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19.6
作者：
Choudhry N;Li K;Zhang T;Wu KY;Song Y;Farrar CA;Wang N;Liu CF;Peng Q;Wu W;Sacks SH;Zhou W
通讯作者：
Zhou W
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Gurtner GC
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64.8
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41.2
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Doloff JC;Veiseh O;Vegas AJ;Tam HH;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 DL;Langer R;Anderson DG
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Anderson DG
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Al Barashdi MA;Ali A;McMullin MF;Mills K
通讯作者：
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