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In Space demonstration of 3D-bioprinted vascularization technique

par Greco, Immacolata
Président du jury Delplancke, Marie-Paule
Promoteur Hendrick, Patrick
Publication Non publié, 2023-09-11

Thèse de doctorat

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Résumé :

In the European Union, Cardio-Vascular Diseases (CVD) are the primary cause of death, accounting for nearly 37% of all deaths in 2017, which translate in 1.71 million fatalities in the. Cancer (malignant neoplasms; 25.0% of all fatalities) is the second most common cause of death. CVD encompass a wide range of medical conditions that affect the circulatory system (the heart and blood vessels), and are frequently the result of atherosclerosis, the abnormal deposition of cholesterol and fatty substances on the inner walls of a person's arteries. The most prevalent circulatory system diseases include ischaemic heart disease (heart attacks) and cerebrovascular diseases (strokes). A substantial percentage of the different cardiovascular disorders are congenital diseases, many of which are incurable and require lifetime specialized care [1]. CVD impose a significant burden on healthcare systems and government budgets. The more accurate recent statistics refer that developed countries spend about 10000$ per cardiovascular-related events. In the USA alone, the costs for tackling CVD account for more than $700 billion. The burden of CVD mortality and morbidity has a significant effect on not only healthcare systems and the quality of life of patients, but also on their productivity and that of their informal carers. Most studies on the burden of cardiovascular disease (CVD) only examine direct costs (relating to devices, technologies, services, and other resources used for the treatment and prevention of CVD). Indirect costs, those resulting from productivity gains or losses due to illness or mortality, are much less studied, despite the fact that productivity loss has a significant negative impact on CVD patients, their families, carers, and society as a whole.At present, CVDs’ treatments includes:• Organ/tissue transplantation.• Surgical replacement with synthetic materials (such as prosthetic heart valves or synthetic vascular grafts).• Concurrent medical therapy [2]However, factors like the steadily growing disparity between the number of patients on the waiting list for organ transplants and the limited amount of donors and the limitations of small-diameter prosthetic vascular grafts including thromboembolism and thrombosis, anticoagulant-related haemorrhage, compliance mismatch, neointimal hyperplasia, and aneurysm formation has strongly affected the efficiency in the implementation of those treatments/countermeasures.In recent years, a new field of medicine known as "tissue engineering" or "regenerative medicine" has risen great hopes. It includes several cutting-edge treatments designed to replace and regenerate diseased cells, tissues, or organs. Despite the exceptional progresses in the field, one of the current limitation of tissue engineering is the insufficient capability of generating vascular graft, which are responsible for the blood and nutrient transport from and to tissue. So far, two possible strategies have been elaborated to tackle this bottleneck: 1. Cell – based strategy: based on the possibility of the endothelial cells to form new vessel [3];2. Scaffold – based strategy: focus on the development of “synthetic” vessels structure [4].The scaffold strategy assure for a higher speed of vascularization, one of the most important factors to discriminate for a successful tissue engineered graft. The above figure shows the main pro and cons of the scaffold-based strategy.Even more recently, the field of regenerative medicine has taken advantage of a new and improved technology that is developing at an exceptional pace: bioprinting. Bioprinting is a branch of regenerative medicine based on the layer-by-layer approach to construct three-dimensional cell cultures, tissues, and, in perspective, fully developed organs. 3D bioprinters use bioinks, printable materials that contains living cells. The bulk of many bioinks are water rich molecules called hydrogels. Hydrogels are widely used in tissue engineering, because of the ability to mimic the extra cellular matrix environment and to promote cellular adhesion and proliferation. In this dissertation, we have contributed to the development of optimal strategies for printing vascular structures using a scaffold-based method that can replicate the behaviour of veins.The thesis comprises three essential sections. The first section focuses on an innovative material applicable to tissue engineering. The composition (bioinks) and topology (scaffold) of porous hydrogel bioink and hydrogel porous scaffold have been studied thoroughly. In addition, we developed the double network technique to meet tissue engineering's mechanical integrity and biocompatibility requirements. The second section concentrates on methods for producing vascular structures, enhancing the bioprinting process's viscosity and flow speed settings before introducing a novel method for producing structures with high shape fidelity.