Putri, Nur Rofiqoh Eviana
(2024)
Additive manufacturing of microchannel scaffolds with improved biocompatibility and nutrient diffusion for tissue engineering.
PhD thesis, University of Nottingham.
Abstract
Scaffold architecture and properties to mimic the native tissue are the key challenges for successful tissue engineering. Improving scaffold architecture by incorporation of microchannels could enhance its nutrient and oxygen diffusion and provide an effective viable cell distribution, which leads to better tissue regeneration. Without vascularisation, the transport of nutrients and oxygen to the cells cannot be optimum, leading to cell death. Several techniques have been developed to fabricate microchannel scaffolds, but they are not able to mimic the complex architecture of the native tissue due to the inflexibility of controlling the structure. To solve those problems, additive manufacturing called three-dimensional (3D) printing offers the ability to fabricate complex microchannel scaffolds and mimic the native tissue in a single printing process. Either directly or indirectly using sacrificial ink, 3D printing has been widely developed and can be used for microchannel scaffold fabrication.
This work aims to fabricate microchannel scaffolds with improved biocompatibility and nutrient diffusion by exploring suitable composite biomaterials and different 3D printing techniques. A natural polymer of gelatin with excellent biocompatibility was combined with another synthetic polymer of poly-trimethylene carbonate (PTMC), and polyethylene glycol diacrylate (PEGDA) to improve its mechanical properties and printability for tissue engineering applications. In addition, the use of water-soluble 4-acryloyl morpholine (ACMO) as a fugitive ink in inkjet printing was used to print sacrificial channels without the use of toxic solvent during the fabrication process.
First, the utilization of digital light processing (DLP) for direct printing of microchannel scaffolds was explored. The nozzle-free technique and direct printing offer a facile process. The perfusable microchannel with the size of 400 µm was obtained using ink formulation of 10% (w/v) gelatin methacrylate (GelMA), 10% (w/v) diacrylated PTMC-polyethylene glycol (PEG)-PTMC, and 20% (w/v) PEGDA with 0.3% (w/v) tartrazine photo-absorber and 1% (w/v) lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) photo-initiator. The obtained scaffold showed controlled mechanical and swelling properties. Immortalized human mesenchymal stem cells (ihMSC) were seeded into the channels and showed cell attachment after 1 day of culture. Bioprinting of the microchannel scaffold using PEGDA and L929 cells was also explored by this method and showed the potential for homogeneous cell distribution.
Besides the direct formation of the microchannel scaffold, the indirect technique using sacrificial ink and inkjet 3D printing to form the microchannel was studied. A dual printhead LP50 inkjet 3D printer was used to print the GelMA/PTMC/PEGDA ink with SUP707 water-soluble ink. The dual printhead enabled two different inks to be printed more precisely and at the same time. By optimizing the printing settings and conditions, the SUP707 ink printed well with different line sizes up to 60 μm. However, it was challenging to print the GelMA-based ink due to the high viscosity of GelMA.
As an alternative, the Dimatix inkjet 3D printer, which has the printhead system with the heater close to the ink reservoir was utilized to print the GelMA ink. Ink formulation of 1.5% (w/v) GelMA, 10% (w/v) diacrylated PTMC-PEG-PTMC, and 20% (w/v) PEGDA was successfully printed at controlled oxygen level and relative humidity during printing. The fugitive ink of ACMO, which is soluble in water made it more biocompatible because the use of toxic solvents or extreme temperatures for removal can be avoided. After water immersion to remove the printed ACMO, the microchannel with the size of 74 µm was created with several complex microchannel designs. The characterization of the scaffold showed improved biocompatibility, mechanical and swelling properties, and perfusion ability.
The results of this thesis showed that the formation of Gelatin/PTMC/PEGDA composite scaffolds fabricated using 3D printing could improve the mechanical properties and printability of the materials. The chemical modification of PTMC and selection of a water-soluble ink could improve its biocompatibility illustrating its suitability as an ink formulation for biological applications. For microchannel scaffold fabrication, inkjet printing had a higher resolution than DLP printing. The ability to do multi-material printing and its high resolution make inkjet printing a suitable method to mimic the vasculature in scaffolds for tissue engineering applications.
| Item Type: |
Thesis (University of Nottingham only)
(PhD)
|
| Supervisors: |
Wildman, Ricky
Rose, Felicity |
| Keywords: |
Microchannel scaffolds; Biocompatibility; Nutrient diffusion; Composite biomaterials; 3D printing techniques; Tissue engineering |
| Subjects: |
R Medicine > R Medicine (General) |
| Faculties/Schools: |
UK Campuses > Faculty of Engineering > Department of Chemical and Environmental Engineering |
| Item ID: |
78692 |
| Depositing User: |
Putri, Nur
|
| Date Deposited: |
31 Dec 2024 04:40 |
| Last Modified: |
31 Dec 2024 04:40 |
| URI: |
https://eprints.nottingham.ac.uk/id/eprint/78692 |
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