Novel Advances in Bioprinting Based on the Mechanical Design and Optimization of Open-source Systems

  1. SODUPE ORTEGA, ENRIQUE
Supervised by:
  1. Alpha Verónica Pernía Espinoza Director
  2. Andrés Sanz García Director

Defence university: Universidad de La Rioja

Fecha de defensa: 29 March 2019

Committee:
  1. Julio Blanco Fernández Chair
  2. Manuel Martínez Torán Secretary
  3. David Cuartielles Committee member

Type: Thesis

Abstract

Three-dimensional (3D) bioprinting promises to be a practical solution for solving the increasing demand for organs and tissues. Several 3D bioprinters with different specifications are commercially available, but the impact on the field of tissue engineering (TE) is still limited, mainly due to the high costs and the unfamiliarity of researchers with this technology. As with the current bioprinters, for many years the access to 3D printers was very expensive and its use was restricted to a few companies and research centers. However, the appearance of open-source 3D printing projects such as Fab@Home or RepRap and commercial desktop 3D printers have permitted to democratize the access to this technology. These printing platforms can serve as a springboard to expand the potential of bioprinting technology to all the scientific community. In that sense, this thesis presents a set of bioprinting tools that include the generation of a fully open-source bioprinting platform and several extrusion-based printheads for the deposition of bioinks and scaffold materials. Moreover, using this open-source printing platform, it was possible to address specific problems for the generation of complex multi-material and cell-laden constructs with high cell-viability percentages. Addressing the complexity of organs and living tissues will require combining multiple building and sacrificial biomaterials and several cells types in a single biofabrication session. This is a significant challenge, and, to tackle that, we must focus on the complex relationships between the printing parameters and the print resolution. We proposed a standard methodology to quantify the print resolution of a bioprinter and establish a comparison framework between bioprinters. The calibration models utilized also permitted to identify which are the most important factors affecting printing accuracy. In this line, an automatic and non-expensive calibration system was also proposed, which can be utilized in bioprinters with multiple printheads. This system permits to obtain faster and more accurate alignment of the printheads, as the whole calibration process is done at once and without manual adjustments. We also performed a comprehensive study of all the parameters involved in the printing process (pressure, temperature, speed, nozzle size and morphology) and including different types of biomaterials. These experiments permitted to understand the influence of each parameter on the printing process and select the optimal configurations for each application. Overall, the contributions presented in this thesis posses the potential to expand bioprinting technology among the TE laboratories. Moreover, it enhances the collective knowledge of the bioprinting community with particular innovative proposals.