Predicting the effect of reduced load level and cell infiltration on spatio-temporal Achilles tendon healing

Mechanobiology plays an important role in tendon healing. However, the relationship between mechanical loading and spatial and temporal evolution of tendon properties during healing is not well understood. This study builds on a recently presented mechanoregulatory computational framework that couples mechanobiological tendon healing to tissue production and collagen orientation. In this study, we investigated how different magnitudes of mechanical stimulation (principal strain) affect the spatio-temporal evolution of tissue production and the temporal evolution of elastic and viscoelastic mechanical parameters. Specifically, we examined the effect of cell infiltration (mimicking migration and proliferation) in the callus on the resulting tissue production by modeling production to depend on local cell density. The model predictions were carefully compared with experimental data from Achilles tendons in rats, at 1, 2 and 4 weeks of healing. In the experiments, the rat tendons had been subjected to free cage activity or reduced load levels through intramuscular botox injections. The simulations that included cell infiltration and strain-regulated collagen production predicted spatio-temporal tissue distributions and mechanical properties similarly to that observed experimentally. In addition, lack of matrix-producing cells in the tendon core during early healing may result in reduced collagen content, regardless of the daily load level. This framework is the first to computationally investigate mechanobiological mechanisms underlying spatial and temporal variations during tendon healing for various magnitudes of loading. This framework will allow further characterization of biomechanical, biological, or mechanobiological processes underlying tendon healing.