Fig. 3: In silico modeling: Identification and validation of an early and transient treatment window where fiber cross-linking modulation can drive tissue repair outcomes.

a Total number of cross-links over time upon regenerative repair, unstructured tissue, and scar repair conditions (n = 7 for each condition). b Simulation results after injury for a Pf=0.7 correspond to scar repair. A transient Pf decrease (Pf = 0.1) during the first 6 days leads to regenerative repair. c Simulation results after injury for a Pf=0.2 correspond to regenerative repair. A transient Pf increase (Pf = 0.8) during the first 6 days leads to scarring repair. d Histogram of the repair index when Pf is constant throughout the simulation (scar and regenerative repair) or for a transient Pf decrease (Pf = 0.1) or increase (Pf=0.8) during the first 6 days. N = 6 simulations for each condition. e Total number of cross-links over time upon regenerative and scar repair or for a transient increase or decrease in Pf. Fixed values of νf = 5 and νad=10^-3 were used for all simulations. n = 6 for each condition. Data are expressed as mean +/− SEM and analyzed by Tukey’s test. ****p < 0.0001.