To improve the predictive capability of pre-clinical models and reduce the use of animal models in drug discovery and disease modelling, advanced in vitro models are being developed. These... Show moreTo improve the predictive capability of pre-clinical models and reduce the use of animal models in drug discovery and disease modelling, advanced in vitro models are being developed. These microphysiological systems (MPS) or “Organs-on-Chip” (OoC) are being developed to include all aspects of the human physiology to improve the in vitro cellular response. OoCs combined with differentiated human induced pluripotent stem cells (hiPSC) allow the use of cells with patient specific genotypes and aid the development of personalized and precision medicine.In this thesis, the development of tractable models of the vasculature is described. These models allow for the combination of hiPSC-derived vascular and tissue specific cells with haemodynamics to recapitulate essential stimuli of blood vessels. Show less
Due to the steep rise of the prevalence of osteoarthritis in the world's population in recent years, it has been of great interest to search for the best way to relieve symptoms and consequences of... Show moreDue to the steep rise of the prevalence of osteoarthritis in the world's population in recent years, it has been of great interest to search for the best way to relieve symptoms and consequences of OA like pain and inflammation. For that reason, the tissue engineering using a porous tri-layer scaffold is a great alternative for patients with this illness.In this way, it was designed, developed and improved a novel chitosan/collagen-based tri-layer porous scaffold with similar chemical composition and structure to the articular cartilage. One of these layers included hydroxyapatite, to promote the integration of growing tissue next to subchondral bone.The biomaterial was physic-chemical characterized, in vitro and in vivo tested obtaining promising results. Later, the scaffold was crosslinked to promote rheological properties that bear the knee cyclic charges while walking. The anti-inflammatory effect was enhanced by the incorporation of a TNF-α blocking drug, which was released in a controlled manner from the material in the damaged tissue over time. The scaffold was non-cytotoxic against chondrocytes and osteoblasts, had great rheological properties and promoted the growth of new cartilage tissue after four weeks after grafted into the osteoarthritic mice knee. Show less
Corneal transplantation still represents the elected method for the treatment of corneal endothelial pathologies. However, the worldwide shortage of donor corneas induced the exploration of... Show moreCorneal transplantation still represents the elected method for the treatment of corneal endothelial pathologies. However, the worldwide shortage of donor corneas induced the exploration of approaches to use the donor tissue more efficiently or to be more independent from donor tissue. This thesis will illustrate the improvements of new strategies for cell-based corneal endothelial regeneration, alternative to corneal endothelial surgical transplantation, by bridging the gap between in vitro experiments and clinical models. In the studies described, we first address the establishment of a GMP-compliant protocol for in vitro hCEC culture for clinical application and then we focus on endothelial cell sheet transplantation, describing both in vitro and in vivo applications of expanded CEC-carriers constructs made by biocompatible materials. Show less
Man, S.; Duffhues, G.S.; Dijke, P. ten; Baker, D. 2019
Pathologies of the respiratory system such as lung infections, chronic inflammatory lung diseases, and lung cancer are among the leading causes of morbidity and mortality, killing one in six people... Show morePathologies of the respiratory system such as lung infections, chronic inflammatory lung diseases, and lung cancer are among the leading causes of morbidity and mortality, killing one in six people worldwide. Development of more effective treatments is hindered by the lack of preclinical models of the human lung that can capture the disease complexity, highly heterogeneous disease phenotypes, and pharmacokinetics and pharmacodynamics observed in patients. The merger of two novel technologies, Organs-on-Chips and human stem cell engineering, has the potential to deliver such urgently needed models. Organs-on-Chips, which are microengineered bioinspired tissue systems, recapitulate the mechanochemical environment and physiological functions of human organs while concurrent advances in generating and differentiating human stem cells promise a renewable supply of patient-specific cells for personalized and precision medicine. Here, we discuss the challenges of modeling human lung pathophysiology in vitro, evaluate past and current models including Organs-on-Chips, review the current status of lung tissue modeling using human pluripotent stem cells, explore in depth how stem cell based Lung-on-Chips may advance disease modeling and drug testing, and summarize practical consideration for the design of Lung-on-Chips for academic and industry applications. (C) 2018 Elsevier B.V. All rights reserved. Show less
