FIGURE 2.

In silico approaches to model the bone healing process and the inflammatory response. (A) Overview of in silico techniques to describe biological processes and predict their different outcomes. The choice of the in silico model depends on the research goal. Continuous models are often used to describe general dynamics at tissue and cellular scales, such as bone mechanics, in which different tissue matrices interplay (figure adapted from Wang and Yang, 2018). Discrete models are mostly used to represent individual behavior at (sub)cellular scales, such as the immune response, which comprises a high number of cells and cytokines. The hybrid approach combines the advantages of both continuous and discrete techniques, providing comprehensive multiscale models that allow to investigate, for instance, sprouting angiogenesis during the bone regeneration process (figure obtained with the model described in Carlier et al., 2016). (B) Flow diagram summarizing the macrophage-mediated inflammation in bone fracture healing described in Trejo et al. (2019). Cells are represented by squares: unactivated macrophages (M₀), classical macrophages (M₁), alternative macrophages (M₂), SPCs (c _m ) and osteoblasts (c _b ). Pro-inflammatory (c₁) and anti-inflammatory (c₂) cytokines are represented by circles. Tissue matrices are represented by hexagons: fibrocartilage (m _c ) and woven bone (m _b ). Debris (D) is represented by a diamond. Adapted from Trejo et al. (2019).