Mechanobiological computational model for the development and formation of sinovial joints

The onset and development of the synovial joints is due to different genetic, biochemical, and mechanical factors. It starts at the limb buds, which have an uninterrupted mass of mesenchymal cells within its core, also known as skeletal blastema. Most of these blastemal cells differentiate into chondrocytes; however, some of these cells remain undifferentiated at the site of the future joint (interzone). The separation of the rudiments occurs with cavitation process within the interzone. After the joint cleavage (cavitation), joint morphogenesis occurs, and the bones take their final shape. Once the embryonic period has finished, the synovial joint and its internal structures has developed completely. Though, once the synovial joints are formed, they might suffer several pathologies, such as the osteoarthritis (OA). There are several treatments that have been proposed to regenerate the articular cartilage, among which scaffolds without cellular sources have shown great results. Understand the processes that the joint tissue goes through are important to develop new direct and effective treatments for joint related pathologies. Computational models seem a good alternative tool to complement the study of the joint processes. Therefore, it was of our interest to study, through computational models, the biochemical interaction for the interzone onset, the cavitation and morphogenesis processes during the joint development. We analyzed these phenomena within the development of an interphalangeal joint and the patella onset. Moreover, we were also interested on analyzing, through a computational model, the processes happening when a defect in the articular cartilage is treated with the implantation of a polymeric scaffold. All the computational models developed in this study applied theories about tissue behavior under mechanical and biochemical stimuli. The obtained results were compared to experimental works found in the literature, all of them showed promising outcomes. Hence, we consider that the procedures and considerations taken for each proposed computational model are not far from what is really happening on the analyzed biological phenomena. Moreover, we were able to evaluate mechanical and biochemical conditions the biological phenomena, that would be hard to test through experimental approaches. We hope that these models become useful to medical and biological researches, helping in the design of prevention and therapy strategies for joint related diseases. This thesis is structured in eight parts including an introduction which tries to aware the importance of the study and the objectives of the thesis. Afterwards, on the second part, we expose some general concepts related to the topics and methods employed to develop the research. Then, the third part describes a computational model proposed to explain joint development from the interzone onset to the cavitation process. The fourth part is focus on the joint morphogenesis as part of the joint development process. Subsequently, the fifth section is dedicated to explaining the sesamoid bones development through a comparison of three theories of the patella onset, evaluated via computational models. The seventh part of this work is a computational model proposed to understand the processes that surround the cartilage regeneration when a polymeric scaffold is implanted in the articular cartilage. In the last part, we concluded the achievements and discussed the main conclusions of the thesis, as well as the recommended future work and perspectives. As an additional chapter, we added a general overview of the thesis in English and in Valencian

• Autores: Márquez Flórez, Kalenia María
• Tipo de recurso: Doctoral thesis
• Fecha de publicación: 2019
• Institución: Universidad Nacional de Colombia
• Repositorio: Universidad Nacional de Colombia
• Idioma: spa
• OAI Identifier: oai:repositorio.unal.edu.co:unal/77329
• Acceso en línea: https://repositorio.unal.edu.co/handle/unal/77329; http://bdigital.unal.edu.co/74996/
• Palabra clave: Synovial joint; Articulación sinovial; Desarrollo articular; Joint development; Biomechanics; Biomecanica; Mechanobiology; Mecanobiología
• Rights: openAccess
• License: Atribución-NoComercial 4.0 Internacional