Experimentally, an in vivo animal model was set up and several animal experiments were conducted to investigate the effect of reduced and unloading on the Achilles tendon, both in intact tendons and in healing tendons at various timepoints.
The main findings on intact tendons are that in vivo unloading results in a more disorganized microstructure and an impaired viscoelastic response. Additionally, unloading also altered the nanoscale fibril mechanical response, possibly through alterations in the strain partitioning between hierarchical levels. Overall, the findings pointed to the importance of spatial heterogeneity within the tissue, where the main response to altered load is altered microstructural arrangement of the collagen. The main findings on healing ruptured tendons are that in vivo unloading during the early healing process resulted in a delayed and more disorganized collagen structure and a larger presence of adipose tissue. Unloading also delayed the remodelling of the stumps as well as callus maturation. Additionally, the nanoscale fibril mechanical response was altered, with unloaded tendons exhibiting a low degree of fibril recruitment as well as a decreased ability for fibril extension. The amount of elastin and collagen I and II is spatial and temporal and effected by unloading of the tissue. We have further developed new methodology where we apply high-resolution synchrotron tissue characterization techniques, combined with in situ mechanical loading, allowing to elucidate the intricate connection between hierarchical scales.
A numerical framework has been developed to investigate the mechanobiology of intact and healing tendon by utilizing and developing advanced numerical models. Our presented finite element mechanobiological framework for Achilles tendon healing is used together with different levels of external loading from the experiments. Predictions of the spatio-temporal evolution of tissue distribution, collagen alignment and mechanical properties overall agreed well with experimental data. Interestingly, both strain-dependent and cell density-dependent tissue production were identified as possible explanations for decreased tissue production in the tendon core during healing. The healing framework was expanded to predict formation of different tissue types during healing. Different mechanobiological factors were explored to regulate the formation of different tissue types, i.e. tendon-, cartilage-, fat- and bone-like tissue. This framework is the first to reproduce experimental observations of these tissues. It provides several potential mechanisms of mechanobiological regulation of the formation of different tissue types during tendon healing.
The details from the experimental data in terms of collagen fiber distribution, anatomy and sub-anatomical details in the tendons are being implemented into the computational models, in order to both unravel the contribution of anatomy, versus structure and composition, as well as how the heterogeneity and twisting of the tendon affects the mechanical ques for mechanobiological adaptation.
