Fig. 1: Tissue mechanics set up morphogenetic field for wound-induced hair follicle neogenesis.

a A PWD28 C57Bl/6 mouse. b AP staining showing de novo hair follicle formation at the center of the wound bed at PWD28. c Schematic diagram showing the location of regenerated hair follicles (blue dots) in b. d Stiffness heatmap overlaying the PWD14 wound. Colorimetric unit: kPa. e Cross-sectional view of the PWD14 wound and distribution of wound stiffness. Yellow arrow heads indicate the formation of hair placodes. Heatmap and number indicate the spatial stiffness of the whole wound bed. Unit: kPa. Green arrow indicates the range of the morphogenetic field. f A Bleb-treated mouse on PWD28. g AP stain showing the number of hair follicles increased significantly upon Bleb treatment. h Schematic diagram of hair follicles (blue dots) in g. i Stiffness heatmap of PWD14 Bleb-treated overlaying wound. j Dot plot showing changes in HF upon Bleb treatment. n = 8 biologically independent animals. Data are presented as mean values ± SEM. p = 0.003, unpaired two-sided t-test. k The area of the wound bed under 15 kPa positively correlates with the number of hair follicles. SHG of l PWD14 and m PWD21 wounds. The color squares indicate the location of corresponding enlarged photos from n PWD14 center, o PWD14 margin, p PWD21 center and q PWD21 margin of the wound image. r Dot plot showing the number of fibers per square unit. PWD14 C/M: p = 0.0323, PWD14/PWD21 C: p = 0.0495, PWD21 C/M: p < 0.0001. s Fiber thickness in respective wound time and location. PWD14 C/M: p = 0.0454, PWD14/PWD21 C: p = 0.0020, PWD21 C/M: p < 0.0461. r, s Data are presented as mean values ± SD. n = 8 regions examined over four biologically independent animals. One-way ANOVA, Tukey test. t Summary graph of wound stiffness on PWD14 and PWD21 with respect to wound location and Bleb treatment. n = 10 regions examined over five biologically independent animals per location per condition. Data are presented as mean values ± SD. *p = 0.0478; **p = 0.0061; ***p < 0.0001. One-way ANOVA, Tukey test. u Illustration of tissue mechanics partake in setting up the morphogenetic field for WIHN. Red line: wound margin. Green: soft, morphogenetic field. Blue: hair placodes. Ctl: control; Bleb: Blebbistatin; HF: hair follicle; sq: square; Lt: left; Rt: right; Morph: morphogenetic. The images in a–i represent 8 out of 8 experiments performed. The images in l–q represent 4 out of 4 experiments performed.