On a multiphysics model of endochondral growth under controlled mechanical load conditions for the evaluation of pathological cases

dc.contributor.advisorTtrabelsi, Olfa
dc.contributor.advisorGarzón Alvarado, Diego Alexander
dc.contributor.advisorHo Ba Tho, Marie-Christine
dc.contributor.authorQuexada Rodriguez, Diego Alfredo
dc.contributor.googlescholarQuexada Rodriguez, Diego Alfredo [X3LWtLQAAAAJ]
dc.contributor.orcidQuexada Rodriguez, Diego Alfredo [0000000309210912]
dc.contributor.researchgroupGrupo de modelado y métodos numericos en ingeniería GNUMspa
dc.date.accessioned2025-08-26T19:13:19Z
dc.date.available2025-08-26T19:13:19Z
dc.date.issued2025-08-03
dc.descriptionilustraciones, diagramas, fotografíasspa
dc.description.abstractEsta tesis investiga la mecanobiología de la placa de crecimiento y su papel en la osificación endocondral, destacando el impacto de los estímulos mecánicos en el desarrollo óseo. La investigación abarca el modelado numérico y la experimentación in vitro para explorar las adaptaciones trabeculares y la mineralización en condrocitos. La primera parte del estudio emplea modelos de elementos finitos para analizar los efectos de la morfología de la placa de crecimiento en el desarrollo del hueso trabecular. Utilizando la densidad de energía de deformación como estímulo de remodelación, las simulaciones revelan que los puentes de osificación se forman en regiones de alto esfuerzo cortante, particularmente en los puntos de inflexión de la placa de crecimiento. Estos hallazgos son relevantes para condiciones como el deslizamiento de la epífisis femoral capital (SCFE) y la enfermedad de Sever. Posteriormente, se introduce un modelo dinámico que incorpora índices osteogénicos para simular la adaptación de la placa de crecimiento bajo carga mecánica. El estudio paramétrico cuantifica los efectos del grosor y la amplitud en la estructura trabecular mediante un análisis de superficie de respuesta, proporcionando información sobre las variaciones en la densidad ósea en respuesta a cambios en la forma de la placa de crecimiento y fuerzas localizadas. La segunda parte de la tesis se centra en la investigación in vitro de células condrogénicas ATDC5, un modelo ampliamente reconocido de osificación endocondral in vitro. Se realizaron experimentos de estimulación mecánica utilizando diversos biorreactores para evaluar cómo la deformación mecánica influye en la mineralización. Los experimentos iniciales con chips microfluídicos de PDMS mostraron limitaciones en la repetibilidad, lo que llevó a un cambio hacia biorreactores comerciales (MECHANOCULTURE T6 y EBERS) y posteriormente, al desarrollo de un biorreactor diseñado a medida. Los resultados indican una correlación positiva entre la estimulación mecánica y la mineralización en cultivos en monocapa, mientras que no se observó un efecto significativo en andamios de colágeno 3D sometidos a compresión pseudo-estacionaria. Estudios preliminares con esferoides celulares sugieren que se forman agregados mineralizados en sus superficies, lo que abre posibilidades para futuras investigaciones. En la parte final de la tesis, se implementó un modelo multiescala para estudiar cómo los estímulos mecánicos pueden alterar distintos procesos a nivel micro y macro. Un resultado significativo de esta tesis, además de las publicaciones, es el desarrollo de un biorreactor novedoso diseñado para facilitar la estimulación mecánica tanto en cultivos celulares 2D como 3D. Diseñado para ser versátil, soporta diversas condiciones de carga, permitiendo la monitorización en tiempo real del cultivo celular a través de una carcasa transparente, y la optimización precisa de los regímenes mecánicos. El sistema garantiza tanto la biocompatibilidad como la reproducibilidad, convirtiéndose en una herramienta valiosa para ensayos de cultivos celulares bajo diferentes regímenes de estimulación. Esta investigación integra el modelado numérico y el trabajo experimental para comprender mejor la mecanobiología de la osificación endocondral. Resalta el papel del esfuerzo cortante en la conformación de las estructuras trabeculares y explora cómo la estimulación mecánica puede influir en la mineralización de los condrocitos. Los resultados muestran cómo la placa de crecimiento se adapta a las fuerzas mecánicas, proporcionando conocimientos que podrían mejorar los tratamientos de diversas condiciones patológicas. Además, demuestra cómo los estímulos mecánicos pueden promover la mineralización a microescala, un proceso clave en la osificación endocondral. (Texto tomado de la fuente)eng
dc.description.abstractThis thesis investigates the mechanobiology of the growth plate and its role in endochondral ossification, emphasizing the impact of mechanical stimuli on bone development. The research spans numerical modeling and in-vitro experimentation to explore trabecular adaptations and mineralization in chondrocytes. The first part of the study employs finite element models to analyze the effects of growth plate morphology on trabecular bone development. Using strain energy density as a remodeling stimulus, simulations reveal that ossification bridges form in regions of high shear stress, particularly at inflection points of the growth plate. These findings are relevant for conditions such as slipped capital femoral epiphysis (SCFE) and Sever's disease. A dynamic model is later introduced, incorporating osteogenic indices to simulate growth plate adaptation under mechanical loading. The parametric study quantifies the effects of thickness and amplitude on trabecular structure through a surface response analysis, providing insights into bone density variations in response to changes in the shape of the growth plate and localized forces. The second part of the thesis focuses on the in-vitro investigation of ATDC5 chondrogenic cells, a well know model of endochondral ossification in-vitro. Mechanical stimulation experiments were conducted using various bioreactors to assess how mechanical strain influences mineralization. Initial experiments using PDMS-based microfluidic chips showed limitations in repeatability, prompting a shift to commercial bioreactors (MECHANOCULTURE T6 and EBERS) and then, a custom-built bioreactor. The results indicate a positive correlation between mechanical stimulation and mineralization in monolayer cultures, whereas no significant effect was observed in 3D collagen scaffolds subjected to pseudo-stationary compression. Preliminary studies with cell spheroids suggest that mineralization aggregates form on their surfaces, offering potential for further investigation. In the final part of the thesis, a multiscale model was implemented to study how mechanical stimuli may alter different processes at the micro and macro-scale. A significant outcome of this thesis, besides the published material, is the development of a novel bioreactor designed to facilitate mechanical stimulation in both 2D and 3D cell cultures. Engineered for versatility, it supports various loading conditions, enabling real-time cell culture monitoring trough a transparent enclosure, and precise optimization of mechanical regimes. The system ensures both biocompatibility and reproducibility, making it a valuable tool for testing cell cultures with different stimulation regimes. This research integrates numerical modeling and experimental work to better understand the mechanobiology of endochondral ossification. It emphasizes the role of shear stress in shaping trabecular structures and explores how mechanical stimulation can influence chondrocyte mineralization. The results show how the growth plate adapts to mechanical forces, providing insights that could improve treatments for different pathological conditions. Furthermore, it shows how mechanical stimuli can promote mineralization at the microscale, a key process in endochondral ossification. Keywords: Mechanobiology, growth plate, endochondral ossification, mechanical stimulation, numerical modeling, in vitro experimentation, bioreactor, chondrocyte mineralization, shear stress, trabecular adaptation, finite elements, SCFE, Sever’s disease, biocompatibility, bone density, cell spheroids, microfluidics, collagen scaffolds, tissue engineering.spa
dc.description.degreelevelDoctoradospa
dc.description.degreenameDoctor en Ingeniería - Ciencia y Tecnología de Materiales
dc.description.researchareaComputational Mechanics
dc.format.extent242 páginas
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/88472
dc.language.isoengspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisherUniversité de technologie de Compiègnespa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.facultyFacultad de Ingenieríaspa
dc.publisher.placeBogotá D.C.
dc.publisher.programBogotá - Ingeniería - Doctorado en Ingeniería - Ciencia y Tecnología de Materialesspa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.licenseReconocimiento 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.ddc620 - Ingeniería y operaciones afines
dc.subject.decsOsteogénesis
dc.subject.decsPlaca de Crecimiento
dc.subject.decsGrowth Plate
dc.subject.decsImagenología Tridimensional
dc.subject.decsImaging, Three-Dimensional
dc.subject.decsTerapia por Estimulación Eléctrica
dc.subject.decsElectric Stimulation Therapy
dc.subject.proposalMecanobiologíaspa
dc.subject.proposalPlaca de crecimientospa
dc.subject.proposalOsificación endocondralspa
dc.subject.proposalEstimulación mecánicaspa
dc.subject.proposalModelización numéricaspa
dc.subject.proposalExperimentación in vitrospa
dc.subject.proposalBiorreactorspa
dc.subject.proposalMineralización de condrocitosspa
dc.subject.proposalTensión de cortespa
dc.subject.proposalAdaptación trabecularspa
dc.subject.proposalElementos finitosspa
dc.subject.proposalSCFEspa
dc.subject.proposalEnfermedad de Severspa
dc.subject.proposalBiocompatibilidadspa
dc.subject.proposalDensidad óseaspa
dc.subject.proposalEsferoides celularesspa
dc.subject.proposalMicrofluídicaspa
dc.subject.proposalAndamios de colágenospa
dc.subject.proposalIngeniería de tejidosspa
dc.subject.proposalMechanobiologyeng
dc.subject.proposalGrowth plateeng
dc.subject.proposalEndochondral ossificationeng
dc.subject.proposalMechanical stimulationeng
dc.subject.proposalNumerical modelingeng
dc.subject.proposalIn vitro experimentationeng
dc.subject.proposalBioreactoreng
dc.subject.proposalChondrocyte mineralizationeng
dc.subject.proposalShear stresseng
dc.subject.proposalTrabecular adaptationeng
dc.subject.proposalFinite elementseng
dc.subject.proposalSever’s diseaseeng
dc.subject.proposalBiocompatibilityeng
dc.subject.proposalBone densityeng
dc.subject.proposalCell spheroidseng
dc.subject.proposalMicrofluidicseng
dc.subject.proposalCollagen scaffoldseng
dc.subject.proposalTissue engineeringeng
dc.titleOn a multiphysics model of endochondral growth under controlled mechanical load conditions for the evaluation of pathological caseseng
dc.title.translatedSobre un modelo multifísico de crecimiento endocondral en condiciones de carga mecánica controlada para la evaluación de casos patológicosspa
dc.typeTrabajo de grado - Doctoradospa
dc.type.coarhttp://purl.org/coar/resource_type/c_db06
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/doctoralThesis
dc.type.redcolhttp://purl.org/redcol/resource_type/TD
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dcterms.audience.professionaldevelopmentEstudiantesspa
dcterms.audience.professionaldevelopmentInvestigadoresspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2

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