Figure 1.

Schematic overview of the in silico clinical trial presented in this study. A previously developed mechanistic model of murine bone regeneration was adapted to describe the aberrant cellular behavior of cells affected by NF1 mutation by altering the corresponding parameter values (inner, blue circle: in silico model). As an example, the inner circle shows how a conceptual model (1) of cartilage generation can be translated in a schematic (2) and mathematical representation (3). By altering the parameter values, various physiological and pathological behaviors can be represented (indicated in green). From the altered in silico model, a cohort of 200 “virtual subjects,” each representing a different parameter combination, was generated. For each virtual subject the bone-healing process was simulated both with BMP treatment and without BMP treatment (outer, green circle: in silico clinical trial).