Development of an agent-based model to recapitulate murine patellar tendon healing as a function of age
The patellar tendon transmits loads from the quadriceps to the tibia promoting locomotion. The main etiological factor behind patellar tendinopathies is thought to be excessive loading and unloading during athletic activity (Pearson & Hussain, 2014). The extracellular matrix (ECM) composition and fibroblast-like tenocytes dictate tendon’s uniaxial mechanical properties (Kannus, 2000). Following injury, a flood of inflammatory cells and spike in certain gene expressions work together to remove damaged tissue, trigger fibroblast proliferation, and deposit a provisional collagen matrix (Thomopoulos et al., 2015). Despite these processes, healed tendons demonstrate significant functional deficits (Mienaltowski et al., 2016). Moreover decrease in cell migration and fiber alignment with age further hampers healing outcomes(Dunkman et al., 2013). Efforts to restore tendon function are impeded by a lack of understanding of the early healing process, which may be age- and sex-dependent (Fryhofer et al., 2016; Mienaltowski et al., 2016). The tendon healing process can be further understood using an agent-based model (ABM). ABMs simulate individual agents and the interactions between them and their environment. This approach has the advantage of building complexity from the ground up, mimicking the underlying tendon physiology (Conte & Paolucci, 2014). Therefore, the objectives of this study were to 1) formulate a literature based ABM of murine patellar tendon healing with varying initial conditions to recapitulate changes observed with aging, and 2) Conduct simulations to determine whether ABM recapitulated salient features of healing, and to make predictions about healing outcomes.