INKJET PRINTING OF MICROVASCULAR TISSUE CONSTRUCTS

UoM administered thesis: Phd

  • Authors:
  • Fei Zheng

Abstract

This thesis presents a study of the fabrication of microvascular networks within a hydrogel matrix using piezoelectric drop-on-demand (DOD) and electrohydrodynamic (EHD) inkjet printing techniques. Gelatin methacryloyl (GelMA) with over 96 % methacrylation degree was prepared as a photo-crosslinkable hydrogel matrix. A cytocompatible gelatin-derived surfactant (GelSurf) was combined with a GelMA aqueous solution. This formulation exhibited satisfactory printability, allowing stable multilayer DOD inkjet printing achieving a feature line width of 88 um. The cytocompatibility of this GelMA-based ink was demonstrated by seeding with NIN/3T3 fibroblasts and human umbilical vein endothelial cells (HUVECs), showing > 95% cell viability over a 7-day culture. Pluronic F127 (PF 127) aqueous solutions were used as a sacrificial material to form vascular channels in hydrogel and polydimethylsiloxane (PDMS) matrices. These show excellent printability with both DOD and EHD inkjet printing, yielding the smallest feature line widths of 32.5 um and 5.2 um respectively. 3D surface analysis and SEM characterisation were performed with the EHD inkjet printed samples to investigate the relationships amongst line width, line height and the number of printing repetitions. Microvascular networks with complex hierarchical geometries were created by casting GelMA hydrogel over the EHD inkjet printed PF 127 fugitive templates. Human dermal fibroblasts (HDFs) were encapsulated within the hydrogel matrix accompanied with the post-seeded HUVECs for the endothelization of the microchannels. The microvascular tissue constructs could be maintained by perfused media over 21 days in culture, exhibiting superior cell viability over the unpatterned matrix controls (92% vs 13%). With the 3D co-culture of HDFs and HUVECs, the perfused microchannels were covered by a confluent endothelium monolayer whilst a surrounding support tissue was formed by the populated fibroblasts. With the use of PDMS silicone, the multilayer EHD inkjet printed structures further presented a capability of fabricating microfluidic chips, which offers a comparable spatial resolution and a simpler manufacturing process in comparison with conventional lithographic methods.

Details

Original languageEnglish
Awarding Institution
Supervisors/Advisors
Award date1 Aug 2020