Development of chitosan based hydrogels as bio-inks for rapid prototyping technologies

Abstract

The ongoing demand of organs is growing significantly in the last years. There are a lot of people who need a transplant and they are in the waiting list because there are not enough donors to supply all the people. For that reason, fields as Tissue Engineering are studying new ways to create or restore tissues and organs. Among them, 3D bioprinting is emerging more popular and it consists in creating 3D tissue constructs with bioink, the material used to print, and pre-designed structures previously designed with computer-aided design. Bioink is a combination of biomaterials and living cells. This project focuses its attention in finding a thermo-sensitive hydrogel, stable liquid solutions at refrigerated temperature that turn into gel upon an increase of temperature. They are composed of chitosan and a polyol-phosphate salt and they must serve as a bioink. Then, with the possible candidates as bioinks, studies of rheology and printability are performed. Three candidates are the best ones to be used as bioinks for their low gelation time, the time in which the solution/gel transition occurs, and their pH similar to the physiological one. Further studies, as degradation tests, allow the selection of two of them as the best candidates. Rheology studies help to understand the flow behaviour of the solutions and the viscoelastic properties of the solutions by measuring the storage modulus, which represents the elastic behaviour of the material, and the loss modulus, which represents the viscous behaviour. Then, an exhaustive study on printability gives the best combinations of parameters that affect the final printed structures that are printed with the two candidates as bioink. These parameters are the state of the ink, the diameter of the nozzle, the addition or no addition of PBS solution to the printbed and the temperatures at which the syringe and the printbed must be. Good results on bioprintring are achieved proving that the two thermo-sensitive solutions composed of chitosan and a polyol-phosphate salt are good candidates as bioinks.