Advanced In-vitro Models with Integrated Sensing for Real-time Monitoring of Electrical and Mechanical Properties of Cellular Constructs
Notice bibliographique
Résumé
The aim of this work of thesis was to contribute to the engineering of physiologically relevant in-vitro models with the design of systems able to mimic and monitor the dynamic environment of cellular constructs. These advanced models are emerging as a powerful solution to bridge the gap between basic and clinical research, currently hindered by the low predictivity and limited successful translation rate of animal models. In particular, a cellular impedance-meter was designed and interfaced with a dual-flow bioreactor to monitor the electrical properties of biological barriers. Indeed, epithelial and endothelial tissue allow the separation of different compartments in the human body and are normally exposed to shear stress on both sides (e.g. blood and interstitial fluid flow). The system was validated with an intestinal model, demonstrating that dynamic conditions contribute significantly to the tightness of the barrier. Possible applications of the system range from drug testing to the study of several pathologic conditions related with an alteration of barrier functions. Since it is well known that mechanical properties of tissues dynamically evolve during growth, ageing or diseases like fibrosis, different methods were investigated to modulate spatial and temporal viscoelastic properties of hydrogel-based scaffolds. In order to monitor mechanical properties of cellular constructs in real-time, the MechanoCulture TR (MCTR) bioreactor was re-engineered in collaboration with the Canadian company CellScale. Finally, a model of liver fibrosis was implemented mimicking in-vitro the ‘healthy’-fibrotic transition with an enzymatic stiffening method and monitoring the mechanical properties of hepatocyte laden gels in the MCTR. The results obtained represent a first step towards physiologically relevant models useful in the understanding of fibrosis mechanobiological mechanisms and progression or in the study of antifibrotic drugs. In conclusion, during the PhD, advanced models with integrated sensing for the real-time monitoring of electrical and mechanical properties of cell construct were designed, tested and validated. The results obtained have relevant implications both in the medical field, contributing to the study of disease development, and in the pharmaceutic and cosmetic fields, providing reliable tools for testing chemical compounds and drugs.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».