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Investigation of Calcium Oxalate Crystallization Under Microfluidic Conditions for the Understanding of Urolithiasis Karol Rakotozandriny

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Investigation of Calcium Oxalate Crystallization Under Microfluidic Conditions for the Understanding of Urolithiasis Karol Rakotozandriny Investigation of Calcium Oxalate Crystallization under Microfluidic Conditions for the Understanding of Urolithiasis Karol Rakotozandriny To cite this version: Karol Rakotozandriny. Investigation of Calcium Oxalate Crystallization under Microfluidic Conditions for the Understanding of Urolithiasis. Human health and pathology. Sorbonne Université, 2019. English. NNT : 2019SORUS347. tel-03141231 HAL Id: tel-03141231 https://tel.archives-ouvertes.fr/tel-03141231 Submitted on 15 Feb 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Sorbonne Université Ecole doctorale 397 : Physique et Chimie des Matériaux Laboratoire de Chimie de la Matière Condensée de Paris Laboratoire de Physicochimie des Electrolytes et Nanosytèmes InterfaciauX Investigation of Calcium Oxalate Crystallization under Microfluidic Conditions for the Understanding of Urolithiasis Etude de la Cristallisation des Oxalates de Calcium en Conditions Microfluidiques pour la Compréhension de l’Urolithiase Par Karol Rakotozandriny Thèse de doctorat de Physique et Chimie des Matériaux Dirigée par Christian Bonhomme et Ali Abou Hassan Présentée et soutenue publiquement le 27 septembre 2019 Devant un jury composé de : M. Bruno BUJOLI Directeur de Recherche Rapporteur Mme Fabienne TESTARD Chercheur CEA Rapporteure M. Karim BENZERARA Directeur de Recherche Examinateur Mme Christèle COMBES Professeur des Universités Examinatrice Mme Annette F. TAYLOR Professeur des Universités Examinatrice Mme Florence BABONNEAU Directrice de Recherche Membre invité M. Ali ABOU HASSAN Maître de Conférences Co-directeur de thèse M. Christian BONHOMME Professeur des Universités Directeur de thèse Table of content Table of abbreviations ........................................................................................................ 3 General introduction ........................................................................................................... 5 Chapter 1 Literature review ................................................................................................ 9 1. The context of the study .........................................................................................13 a. The nephron: the functional unit of the kidney ........................................................13 b. Development of nephron-on-a-chip technology to mimic the renal function ............14 c. The kidney stone disease: a microfluidic strategy ...................................................19 2. The crystal growth of calcium oxalate systems .......................................................24 a. The calcium oxalate crystals, CaC2O4∙nH2O ...........................................................24 b. The origin of calcium oxalate stone formation .........................................................28 c. In vitro calcium oxalate crystallization methods ......................................................36 3. The hydroxyapatite: a calcium phosphate mineral of interest .................................51 a. The calcium phosphates in the field of biomineralization ........................................51 b. The Randall’s plaque ..............................................................................................54 4. Conclusion .............................................................................................................59 Chapter 2 Calcium oxalate crystallization in a microfluidic platform: proof-of-concept .............................................................................................................................................71 1. Inducing calcium oxalate crystallization under microfluidic confinement .................75 a. The microfluidic methodology .................................................................................75 b. The physicochemical strategy for calcium oxalate crystalluria ................................78 2. Influence of hydrodynamics on calcium oxalate crystallization ...............................88 a. The effect of the hydrodynamics .............................................................................88 b. The growth kinetics of calcium oxalate crystal ........................................................97 c. Numerical approach of calcium oxalate crystallization in a micro-reactor ............. 104 3. Conclusion ........................................................................................................... 110 Chapter 3 Microfluidic and biomimetic approaches of the Randall’s plaque ............... 117 1. The hydroxyapatite: a model system for the Randall’s plaque .............................. 121 a. The Randall’s plaque ............................................................................................ 121 1 b. Towards an in vitro and biomimetic strategy ......................................................... 129 2. The heterogeneous growth of calcium oxalate crystals ........................................ 136 a. Calcium oxalate crystallization under micro-confinement...................................... 136 b. The dissolution rate of the Randall’s plaque-like model regarding calcium oxalate crystallization ............................................................................................................... 146 3. Conclusion ........................................................................................................... 152 Chapter 4 Modulation of calcium oxalate crystallization by additives: the effect of green tea ...................................................................................................................................... 159 1. Effect of green tea on calcium oxalate crystallization under microfluidic confinement ……………………………………………………………………………………………..163 a. The catechins: polyphenolic compounds from green tea ...................................... 163 2+ 2- b. Calcium oxalate crystallization under co-laminar mixing of Ca (GT) and Ox (GT) in green tea solution ........................................................................................................ 165 2. Calcium oxalate crystallization from the apatitic layer mimicking the Randall’s plaque: a preliminary study in presence of green tea ................................................................... 173 a. Heterogeneous calcium oxalate crystallization in green tea solution .................... 173 b. Preliminary investigation under microfluidic confinement ...................................... 176 3. Conclusion ........................................................................................................... 180 General conclusion .......................................................................................................... 183 Appendix ........................................................................................................................... 187 2 Table of abbreviations ACO: Amorphous calcium oxalate CAOnh: Anhydrous calcium oxalate CaOx: Calcium Oxalate CaP: Calcium Phosphate CCM: Constant Composition Method COD: Calcium Oxalate Dihydrate COM: Calcium Oxalate Monohydrate COT: Calcium Oxalate Trihydrate EDS: Energy-dispersive X-ray FMCG: Flow Model of Crystallization in Gels GT: Green tea HAp: Hydroxyapatite KS: Kidney Stone Solubility product constant of Calcium Ksp(CaOx): Oxalate MSMPR: Mixed Suspension Mixed Product Removal OCP: Octacalcium Phosphate Pe: Péclet number Re: Reynolds number RP: Randall’s plaque SBF: Simulated Body Fluid SEM: Scanning Electron Microscopy SS: Supersaturation XRD: X-ray Diffraction 3 4 General introduction General introduction Urolithiasis, else known as the kidney stone disease, is the cascade of events occuring in the kidney leading to the pathological formation of solid concretions in the urinary tracts. This disease has been a plague for mankind throughout history1. From ancient Egypt to modern age, major figures experienced the disease such as Ramesses II, Isaac Newton, Charles Darwin or Benjamin Franklin. Over the past fifty years, the kidney stone disease has affected about 10% of the industrialized populations with a global increase in prevalence2. A prevalence study, launched in 2012 in the United States of America, pointed out that men were more likely to develop kidney stones compared to women (10.6% vs. 7.1%)3. Moreover, the same study showed that overweight persons were more affected than normal-weight ones (11.2% vs. 6.1%). The etiology of the disease is complex and can be due to various causes such as low diuresis or imbalance diet4-6. Yet, treatments have been rapidly developed to counter-act the occurrence of kidney stones, e.g. ureteroscopy, shockwave lithotripsy or open surgery. Nevertheless, these treatments represent a physical burden for the patients and an economic one for the health insurance7. Kidney stones are known to exhibit a heterogeneous chemical composition with organic and inorganic species. In-depth chemical characterization of the inorganic compounds showed that calcium oxalate (CaOx) and calcium phosphate (CaP) crystals stand for ≈ 70%
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