Resumen de Mechano-electrochemical analysis of articular cartilage: 3d computational modelling and experimental characterization
The articular cartilage is a complex and highly specialized tissue that covers the ends of bones in synovial joints. Its main function is to provide a lubricated surface to make possible the relative movement between ends of Joints. Its specific nature without blood vessels or nerve endings makes necessary a self-maintenance of the cartilage based on diffusive-convective processes. Diseases such as osteoarthritis, progressive degeneration of the tissue due to the lack of mobility and overweight in obesity condition, among other health disorders, generate the homeostatic imbalance of the tissue.
Although the essential role of articular cartilage has been widely demonstrated to ensure joint health, there is not a deep understanding of the main phenomena that occur for tissue maintenance; which factors promote its deterioration and, the different alternatives for its regeneration. In fact, the lack of effective treatments for cartilage recovering, makes this tissue a target for chronic and disabling diseases in adults.
To provide some insights into these investigations, several computational models have been developed in the last decades. From fiber-reinforced poroelastic models focused in the mechanical behavior of collagen fibrous matrix, to more complex ones, where a detailed correlation between each component and the specific influence in cartilage behavior is addressed. However, important drawbacks are found in most of them; (i) Essential electrochemical phenomena such as the repulsion of fixed charges attached to proteoglycans usually are not considered in articular cartilage simulations. Besides, to analyze the main cartilage disorders, it is necessary to include the influence of each component (water, cations, anions and collagen matrix) as well as the different phases (fluid, solid and ionic phases) into computational models of cartilage; (iii) Not considering these both aspects prevents their application to the study of cartilage diseases. (iv) So far, material model selection and cartilage properties to include in computational modeling are based on the specific research question to study. The individual effect of considering each mechano-electrochemical parameter into cartilage simulations remains unclear.
Thus, in this Doctoral Thesis a three-dimensional mechano-electrochemical model was developed, solved and implemented using the Finite Element Method, with the aim of elucidating these aspects and propose new advances in its study and treatment. This is capable of predicting the behavior of articular cartilage and the specific influence of its mean components. To this end, a multiphasic model was considered, composed of a solid phase (collagen fibers and negative attached proteoglycans), a liquid phase (water) and an ionic phase (Na+, Cl-, etc.).
The computational model includes the ionic convection-diffusion phenomenon, the negative charges attached to proteoglycans and the tissue deformation due to mechano-electrochemical process developed in the tissue. Subsequently, the computational model was applied to the study of the behavior of healthy tissue, different stages of osteoarthritis disease and patients whose joints have been immobilized. The simulation results obtained showed a significant increment of cartilage swelling when increasing the grade of the disease and/or the immobilization time of the patient. Thus, swelling phenomenon has been proposed as a possible biomarker to establish the grade of tissue degeneration. The developed model was also applied to the study of tissue mechano-electrochemical alterations that occur as a result of cartilage overweight due to obesity. Great similarities in ions fluxes and cation distribution within cartilage samples, with early grades of osteoarthritis, led us to suggest the necessity of including preventive treatments in obese people to avoid tissue degeneration. Furthermore, a parametric analysis of articular cartilage properties was addressed, establishing some basic guidelines to select the cartilage properties to incorporate into simulations.
In parallel to that computational research, several experiments were developed to characterize and study in-vitro the articular tissue. The measured heterogeneous properties were also incorporated to the computational model to consider the tissue anisotropy and the simulated results were compared to those obtained considering the articular cartilage as isotropic. Results showed how anisotropy consideration offered a more accurate manner to capture tissue behavior. Finally, this Thesis includes the definition of new biomaterials such as the polyhydroxietil acrylate and polyethil acrylate and collagen-based matrix, their experimental characterization and computational modeling with the aim of analyzing and confirming the viability of these materials for biomedical application as implants to articular cartilage repair. Specifically, for collagen lattices, a novel model to simulate contraction process due to migration, proliferation and cell-exerted forces of embedded cells has been developed.
