Fetal development, mechanobiology and optimal control processes can improve vascular tissue regeneration in bioreactors: An integrative review

Vascular tissue engineering aims to regenerate blood vessels to replace diseased arteries for cardiovascular patients. With the scaffold-based approach, cells are seeded on a scaffold showing specific properties and are expected to proliferate and self-organize into a functional vascular tissue. Bioreactors can significantly contribute to this objective by providing a suitable environment for the maturation of the tissue engineered blood vessel. It is recognized from the mechanotransduction principles that mechanical stimuli can influence the protein synthesis of the extra-cellular matrix thus leading to maturation and organization of the tissues. Up to date, no bioreactor is especially conceived to take advantage of the mechanobiology and optimize the construct maturation through an advanced control strategy. In this review, experimental strategies in the field of vascular tissue engineering are detailed, and a new approach inspired by fetal development, mechanobiology and optimal control paradigms is proposed. In this new approach, the culture conditions (i.e. flow, circumferential strain, pressure frequency, and others) are supposed to dynamically evolve to match the maturity of vascular constructs and maximize the efficiency of the regeneration process. Moreover, this approach allows the investigation of the mechanisms of growth, remodeling and mechanotransduction during the culture.