Extended Data Fig. 4: Return of dermal wrinkles to baseline after treatment with low dose COL1A1-EVs.

a, Wrinkles were tracked on days 0, 4, 7, 14, 21, 28, 35, 42, 49, and 56 d after the indicated treatments (5 low-dose injections of COL1A1-EVs (2.7E9 copy number COL1A1 mRNA), COL1A1-LNPs (2.7E9 copy number COL1A1 mRNA), unloaded EVs, 0.05% retinoic acid [RA], saline). n = 4, Scale bar, 5 mm. Female nude mice that were not exposed to UV comprised the sham group. b, Numbers of wrinkles on the dorsal skin of the mice over time. (n = 4 for all groups; **P = 0.008 COL1A1-EVs vs Saline at day 7; **P = 0.004 COL1A1-EVs vs Saline at day 21, **P = 0.001 COL1A1-EVs vs Saline at day 35; ***P < 0.001 COL1A1-EVs vs Saline at days 14, 28, 42, and 49; ^†P = 0.025 RA vs Saline at day 21; ^††P = 0.007 RA vs Saline at day 28; ^##P = 0.0071 Unloaded EVs vs Saline at day 14; ^##P = 0.004 Unloaded EVs vs Saline at day 21; ^##P = 0.002 Unloaded EVs vs Saline at day 28; ^#P = 0.015 Unloaded EVs vs Saline at day 35; ^※※P = 0.0053 COL1A1-LNPs vs Saline at day 14; ^※※P = 0.0041 COL1A1-LNPs vs Saline at day 21; ^※P = 0.017 COL1A1-LNPs vs Saline at day 28; ^※P = 0.022 COL1A1-LNPs vs Saline at day 35). c, Total wrinkle area (n = 4 for all groups, *P = 0.012 COL1A1-EVs vs Saline at day 7; ***P < 0.001 COL1A1-EVs vs Saline at days 14, 21, 28 and 35; *P = 0.015 COL1A1-EVs vs Saline at day 42; ^††P = 0.008 RA vs Saline at day 14; ^††P = 0.007 RA vs Saline at days 21 and 35;^††P = 0.005 RA vs Saline at day 28; ^#P = 0.012 Unloaded EVs vs Saline at day 14; ^#P = 0.035 Unloaded EVs vs Saline at day 21; ^##P = 0.002 Unloaded EVs vs Saline at day 28; ^※P = 0.062 COL1A1-LNPs vs Saline at day 14; ^※P = 0.039 COL1A1-LNPs vs Saline at day 21; ^※※P = 0.0027 COL1A1-LNPs vs Saline at day 28; ^※※P = 0.046 COL1A1-LNPs vs Saline at day 35). All data are from three independent experiments and are presented as means ± SEM. Two-way ANOVA was used for the comparisons in (b, c).