Development of a 4D Printed Thermo-Responsive Hydrogel for Tissue Engineering

The imbalance between the number of donors and people waiting for organ transplantations is a global problem. There is not a single country in which donor rates come close to supplying the demand for human organs and tissues. The most viable solution to this global problem is the artificial production of organs and tissues, so-called tissue engineering. Tissue engineering an interdisciplinary field between engineering and life sciences. Its goal is to produce cell-containing structures able to restore, maintain, or improve damaged tissues or whole organs. Skin and cartilage are examples of human tissues produced by tissue engineering that are already commercialized, however other tissues such as blood vessels and thicker tissues require a more complex combination of features that have not yet been mastered for production. Blood vessels receive special attention because they are the main constituents of the vascular system, which is the basis to produce thicker tissues and organs such as the heart, liver, kidneys, and others. Based on this need and recent advances in the field of additive manufacturing, such as 4D printing, it was defined as the objective of this work to 4D print a hydrogel responsible for thermal stimuli capable of generating vascular-like conduits that mimic human blood vessels. For this purpose, a photocurable hydrogel composition based on N – Isopropylacrylamide (NIPAM) will be developed. NIPAM is a polymer that responds to temperature stimulus in the range of 32 ˚C, has a well-defined structure and known properties. The hydrogel will be manufactured by digital light processing. It will be printed flat sheets that will fold into cylinders such as vascular-like conduits after thermal stimulation. The obtained structures will be subjected to analyzes of its folding and swelling behaviors, the identification of the trigger temperature that leads to the folding behavior, which is dependent on the hydrogel processing parameters, the swelling ratio of the hydrogel, its ability to be sutured and a tensile test to verify if it can withstand blood flow. It is expected that from the stacking of successive hydrogel sheets colonized with different cell types to obtain a faithful reconstruction of the several different layers that compose a blood vessel. It is also expected that the vasodilation behavior can be partially recreated by the responsive behavior of NIPAM, as well as the determination of the composition and processing parameters leads to the approximation of the mechanical properties necessary for the use of the hydrogels as vascular-like conduits.