Fig. 1: Pathological FBR in humans is mediated by RAC2 mechanotransduction signalling, regardless of implant properties, and is associated with increased mechanical signalling.
a, Trichrome staining of fibrotic capsules from the fibrous capsule formed around silicone-based breast implants, titanium-based pacemakers and stainless-steel-based orthopaedic implants are all similar to one another. Implant located at the bottom of each image. Scale bar, 200 µm. b,c, Quantification of collagen (b) and mature collagen (c) shows no significant differences between the different types of human implant. For breast implants, n = 6 independent capsules; cardiac pacemakers, n = 4 independent capsules; neurostimulators, n = 4 independent capsules; and orthopaedic hardware, n = 5 independent capsules. d, Heat map of the top-100 genes upregulated in Baker-IV versus Baker-I breast implants, organized in decreasing order of P value. e,f, Pathways significantly upregulated in Baker-IV (e) or Baker-I (f) samples analysed using DAVID. Selected pathways highlighted in red are mechanotransduction pathways and those highlighted in green are inflammatory pathways. g, Selected cell-activating and inflammatory genes upregulated in Baker-IV (red) (n = 10 independent capsules) versus Baker-I (grey) capsules (n = 10 independent capsules; RAC2, *P = 0.241; PLAUR, *P = 0.0388; CXCR4, *P = 0.0332; CD44, P = 0.052; PDGFRA, P = 0.0585; MIF, *P = 0.0211). h, STRING analysis showing that RAC2 is a central mechanotransduction mediator of both cell-activating and inflammatory signalling genes that were all upregulated in Baker-IV specimens. STRING analysed interactions between the different genes based on experimental evidence and predicted interactions. Statistical comparisons for b and c were made by using a one-way ANOVA with Tukey’s multiple comparisons tests; statistical comparisons for g were made using a two-tailed t-test comparing Baker-IV with Baker-I samples for each gene. Each data point represents an independent capsule from a different patient. All data represent mean ± s.e.m. Representative images are shown across all experiments. NS, not statistically significant.
