3D printed hydrogels as components in magnetically responsive cell supports for tissue engineering

Extrusion-based printing is a technique used to fabricate three-dimensional (3D) structures in layer-by-layer deposition of material. This approach proves particularly advantageous for printing hydrogels as it can print wide range of viscosities by adjusting parameters such as: temperature, pressure and printing speed. This adaptability enables the precise creation of complex and intricate structures, making it a versatile choice for printing hydrogels. Hydrogels have received significant attention owing to their resemblance to the extra-cellular matrix (ECM), making them promising substrates for promoting cell growth and their responsiveness to external stimulus. Incorporation of magnetic nanoparticles within hydrogels introduces a new dimension to their functionality, enabling the modulation of their behaviours in the presence of external magnetic fields. This leads to the overall objective of the thesis which is to develop a 3D printable hydrogel as component of magnetically responsive cell support to trigger cell growth and differentiation in situ by manipulating external magnetic fields. The first part of the thesis is focused on developing composite hydrogels by bringing together the properties of two polymer types: one a physical micelle-based shear thinning and the other crosslinkable, in one system to obtain an extrusion compatible hydrogel. Formation of self-supporting hydrogels using Pluronic F127 and functionalized-PEG with varying concentration and molecular weight was tested. The arrangement of these polymers in a composite system was studied using Small Angle X-ray Scattering (SAXS). Subsequently analysis of responsiveness of the composite hydrogel to change in temperature and high shear rates was undertaken through rheological measurements. Finally, the printability of the composite hydrogels is assessed by varying printing parameters and obtaining a multi-layered complex printed structure. The outcomes led to an understanding that inclusion of PEG in the hydrogel induced a higher degree of structural organization, reflected in enhanced ordering seen across all composition, however at the same time providing a disruptive part to the included micelles. Sensitive balance of the two components played crucial part in the final properties of thus formed hydrogel. The second part of the thesis focuses on synthesizing, printing and crosslinking of biocompatible GelMA and Gelatin hydrogels. This was followed by incorporation of magnetic nanoparticles in GelMA and Gelatin hydrogels to achieve a ≥ 10 °C hyperthermic temperature jump upon alternating magnetic field. Also, to achieve long-tern stability of thus formed magnetic-hydrogels, crosslinkability of the hydrogels was tested. Additionally, responses of magnetic printed and crosslinked hydrogels were measured in situ in a live cell alternating magnetic field (LC-AMF) environment. Later, printing of magnetic and non-magnetic hydrogels in a single two component extrusion print from two nozzles and in a core-shell format, co-axial printing was performed. The challenges encountered during co-axial printing were evaluated by performing computational fluid dynamics (CFD) simulations. The rheological measurements alone do not directly indicate the optimal parameters for co-axial printing. Therefore, conducting computational fluid dynamics (CFD) simulations offers an efficient means to save time and materials. These simulations provide valuable insights into the forces exerted on hydrogels during the printing process, especially when various printing needle geometries and temperatures are used. Consequently, these simulations will also facilitate the selection of hydrogels suitable for co-axial printing.