Biomechanics of Contemporary Implants and Prosthesis: Modeling, Experiments, and Clinical Application

Modern medicine is now more oriented towards patient-based treatments. Taking into account individual biological features allows for increasing the quality of the healing process. Opportunities for modern hardware and software allow not only the complex behavior of implants and prostheses to be simulated, but also take into account any peculiarities of the patient. Moreover, the development of additive manufacturing expands the opportunities for materials. Technical limits for composite materials, biomaterials, and metamaterials are decreasing. On the other hand, there is a need for more detailed analyses of biomechanics research. A deeper understanding of the technological processes of implants, and the mechanobiological interactions of implants and organisms will potentially allow us to raise the level of medical treatment. Modern trends of the biomechanics of contemporary implants and prostheses, including experimental and mathematical modeling and clinical application, are discussed in this book

Design, Optimization, and Evaluation of a Fusionless Device to Induce Growth Modulation and Correct Spinal Curvatures in Adolescent Idiopathic Scoliosis

RÉSUMÉ La scoliose est une déformation musculo-squelettique complexe et tridimensionnelle de la colonne vertébrale. Les mécanismes de progression de la scoliose sont liés au principe de Hueter-Volkmann. Selon cette théorie, les chargements asymétriques des plaques de croissance altèrent la croissance du rachis (cunéiformisation des vertèbres). Une courbure scoliotique présentant un angle de Cobb supérieur à 50° nécessite généralement une intervention chirurgicale avec fusion rachidienne. Cette chirurgie implique des procédures particulièrement invasives et coûteuses, ce qui a incité plusieurs chercheurs à tenter de développer d‘autres alternatives. Des techniques minimalement invasives et sans fusion ont ainsi été élaborées pour contrôler et corriger un mauvais alignement de la colonne vertébrale avant qu'une progression trop importante des déformations scoliotiques ne se produise. Ces techniques tentent d'exploiter la croissance vertébrale résiduelle afin de corriger la cunéiformisation locale et d‘aboutir à un réalignement progressif du rachis. Les traitements sans fusion semblent également mettre en péril la santé du disque intervertébral à long terme et se limitent à une correction 2D (plan frontal) de déformations intrinsèquement 3D. Mieux comprendre biomécaniquement la progression des déformations scoliotiques permettrait de développer des dispositifs sans fusion plus efficaces. Cela serait une contribution importante et innovatrice à l'amélioration du traitement de la scoliose idiopathique adolescente (SIA). L'objectif global de cette thèse était le développement, l‘optimisation, et l‘évaluation expérimentale d'implants sans fusion afin de moduler la croissance et de corriger les déformations scoliotiques. Les objectifs spécifiques étaient de 1) développer un modèle par éléments finis (MEF) de la colonne vertébrale intégrant une modélisation de la croissance; 2) exploiter ce MEF pour étudier les facteurs biomécaniques impliqués dans les mécanismes de progression de la SIA; 3) exploiter le MEF pour analyser la biomécanique des dispositifs sans fusion existant actuellement et repérer les améliorations pouvant être apportées à ces dispositifs; et 4) exploiter la plate-forme de conception conçue (analyses in silico, in situ, et in vivo) pour développer, optimiser, et valider de nouveaux dispositifs sans fusion modulateurs de croissance pour la correction des déformations de la SIA.----------ABSTRACT Scoliosis is a spinal musculoskeletal deformity defined by a 3D deformity of the spine. The pathomechanism of scoliotic progression may be in part explained by the Hueter-Volkmann principle. This theory describes how increased loading of growth plates will reduce regular growth rates while the converse is also accurate. Further, when extended to the pathogenesis of scoliosis, it defines how asymmetric loading of the vertebral bodies leads to the progression of the deformity via vertebral wedging. Currently, a scoliotic curve reaching a magnitude of 50° Cobb deformation requires surgical intervention involving instrumentation and spinal fusion. The process of fusion is among the most invasive and expensive procedures, which has motivated several researchers to develop other alternatives. The development of a less invasive technique, to control and correct a spinal misalignment before undesirable progression occurs, has subsequently been explored. Several fusionless devices have been developed that attempt to manipulate vertebral growth to correct vertebral wedging and, consequently, realign the spine. However, to date, these approaches have yet to be adopted in a clinical context. Moreover, devices actively pursued seemed to imperil the long term health of the intervertebral disc while corrective attempts are restricted to the unilateral manipulation of a 3D deformity. Therefore, enhanced biomechanical understanding of AIS pathomechanism in conjunction with the development of early and less invasive interventions would offer an important contribution to the improved treatment of AIS. The global objective of this thesis was to design, optimize, and evaluated experimentally fusionless device concepts to induce growth modulation and correct spinal curvatures in adolescent idiopathic scoliosis (AIS). The specific objectives were to: 1) develop a FEM of the spine with integrated growth dynamics; 2) exploit the FEM to explore biomechanical factors involved in the pathomechanism of AIS; 3) exploit the FEM to analyze biomechanically current fusionless growth sparring devices to identify available avenues of improvement; and 4) exploit the devised developmental platform (in silico, in situ, and in vivo analyses) to develop, optimize, and validate novel and improved fusionless growth modulating devices for AIS

Engineering an Ex-Vivo System to Study Transport Phenomena in the Human Intervertebral Disc

Back pain is the leading cause of disability worldwide, entailing a significant socioeconomic impact. A primary source of back pain can be attributed to intervertebral disc (IVD) degeneration allowing nerve ingrowth, facet joint arthritis, disc bulging, and osteophyte formations that press on nearby nerve roots or the spinal cord. While several methods like conservative therapy, discectomy, IVD replacement, and spinal fusion exist to alleviate back pain, no solution has been found to eliminate the pain and return the IVD to its full function. Stem cell injections administered in the IVD have emerged as an attractive option to treat back pain compared to the conventional invasive methods. These injections can retain tissue hydration, improve the IVD’s height, and alleviate pain. However, the IVD is prone to dehydration and calcification that inhibit nutrient transport and metabolite removal. Limitations in solute transport can thus render the IVD’s microenvironment inhospitable to the injected cells. This dissertation first introduces the solute transport conundrum in the literature, including conventional knowledge and methods to study transport. We then discuss the utilization of a whole organ bioreactor in the study of transport. The bioreactor provides a way to define the IVD's microenvironment, mimicking in vivo conditions in humans. In addition, the dissertation includes three manuscripts on the effects of culture conditions on IVD cells, cryopreservation of the IVD, and finite element modeling of solute transport. All of this work ties into the theme of engineering a platform for the ex vivo study of nutrient transport in human intervertebral discs. Manuscript one in Chapter 3 discusses the impact of cell culture conditions on phenotypic changes in IVD cells, activation of different metabolic pathways, and remodeling of the extracellular matrix (ECM). Current culture conditions fail to represent the IVD's in vivo microenvironment and lacks standardization. Cells in the IVD's outer annulus fibrosus (AF) and cartilaginous endplate (CEP) exist in well-oxygenated and nourished conditions compared to the inner AF and nucleus pulposus (NP). I discovered that the modulation of glucose levels every three days induced oxidative stress leading to senescence in AF but not in NP cells. Culture conditions also influenced the metabolic pathways in each cell type in which steady levels of glucose increased AF metabolic activity and remodeling of the ECM compared to NP cells. This study highlights the importance of the in vivo quasi-steady state nutrient transport conditions in IVD cell and tissue cultures experiments. In manuscript two (Chapter 4), I describe a novel method to cryopreserve IVDs at -80ᵒC while maintaining high cell viability. This will allow us to ship and store fresh human cadaveric IVDs until we have bioreactor space and experimental demand. The bioreactor system was utilized to compress bovine IVDs enhancing transport of the cryoprotectant (CPA) transport, reducing CPA cytotoxic effects, and increasing CPA penetration in the inner AF and NP. Our results showed a 95% improvement in the penetration of the CPA in the IVD’s soft tissue. Improving the CPA’s penetration resulted in cell viability equivalent to the fresh control, averaging 80%. This novel cryopreservation technique aims to improve the logistics of obtaining and storing human IVDs for research and clinical purposes. Specifically, this method enables convenient and flexible use of a whole human IVD bioreactor. Next, manuscript four in Chapter 5 examines the development of a patient-specific model of IVD nutrient transport to select appropriate patients and determine optimal cell dose for stem cell therapy. This model is intended to be validated using the bioreactor system. The model used Magnetic Resonance Imaging (MRI) data to generate patient-specific solute transport models, factoring in the exact IVD geometry, water content, and diffusion coefficients, thus providing a realistic representation of solute transport in the human IVD. This model provides a better alternative to study transport phenomena in the human IVD compared to animal models and can be used to infer factors that impact transport. The model will be validated and improved in conjunction with bioreactor experiments. I conclude the dissertation with two proposals to improve this work. One is related to the creation of an intact IVD organ bank, and the second discussed the development of a clinically viable finite-element model to deduce transport information in patient IVDs. The second topic will show how all of the work presented in this dissertation feeds into an engineered ex-vivo platform for studying transport phenomena in human IVDs