|M.Sc Student||Bullkich Elad|
|Subject||A Mechanobiological Feedback Model for Soft Tissue|
|Department||Department of Biomedical Engineering||Supervisors||Professor Eitan Kimmel|
|Dr. Saar Golan|
|Full Thesis text|
Pressure ulcers (PUs) and their ramifications are a key challenge in modern medicine. Computational models significantly promote the study of PUs and their contributing factors (e.g., cellular deformation and oxidative stress). Nevertheless, these models are still lacking in recapitulating the actual kinetics of PU progression. A novel multi-hierarchic PU model is introduced correlating cell with corresponding tissue characteristics by integrating several key mechanisms: linking cell membrane permeability and tissue-level diffusivity to model macro-scale mass transport (Fick’s laws), reperfusion effects (including beneficial) considering the tissue full unloading history, death ligands and alarmins signaling (cellular communication), A Von-Mises-alike hyperspace vitality (failure) criterion for programmed cell death (extended to necrosis) and dynamic strain adaptation that is based on the constitutive biomechanical behavior of passive muscle (PM). Model validation demonstrates excellent agreement with numerous classic cases and recent PU literature (numerical and experimental studies). In particular, it is demonstrated for the first time, the possibility to recapitulate the Boltzmann sigmoid decreasing function characteristic of the critical applied external pressure required for ulceration as a function of pressure application duration. The key mechanisms relative contributions to ulceration are examined and show that: 1. dynamic strain adaptation that is based on PM behavior must be employed during both loading and unloading stages for recapitulating the phenotypic cell death. 2. Modelling tissue effects improves agreement with experimental data by more than 30%. Thus, an improved platform is presented that can better support PU study. Since in this work, tissue as well as cells is modeled, the contribution constitutes a functional framework for future integration of tissue-scale mechanisms such as muscle repair via stem cell proliferation and differentiation.