Fig. 2: Altering extrinsic tissue-scale forces using MSIs produces a human-like FBR capsule architecture in mice.
a,b, FEM of murine (a) and human (b) implants showing that human implants are subject to 100-fold higher mechanical stress than murine implants. c, Schematic and picture of the MSI model. FEM confirming that MSIs recreate human levels of mechanical stress in the mouse. Sx refers to the mechanical stress in the x direction. d, Trichrome staining of FBR capsules in the human implant capsules, SM model and the MSI murine model. Scale bar, 50 µm. e, Herovici staining showing mature (red) and immature (blue) collagen. Scale bar, 50 µm. f, Immunostaining for αSMA, a marker for myofibroblasts. Scale bar, 50 µm. Implant located at the bottom of each image. g, SEM imaging of the surface of the capsules. Scale bar, 10 μm. h, Top: quantification of percent area positive for collagen in each capsule (far right; n = 5 biological replicates for each group; *P = 0.0261, **P = 0.0012). Second from top: quantification of mature collagen deposition in the FBR tissue (far right; n = 5 independent capsules per group; **P = 0.0044). Third from top: quantification of αSMA normalized to cell density using image analyses in each capsule (n = 5 biological replicates for each group; **P = 0.0028). Bottom: quantification of surface collagen percent area associated with each capsule (n = 8 biological replicates for each group; ****P < 0.0001). Statistical comparisons were made by using a one-way ANOVA with Tukey’s multiple comparisons tests. Each data point represents an independent capsule from a different patient or mouse. All data represent mean ± s.e.m. Representative images are shown across all experiments. H, human.
