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- Biofabrication (2) (entfernen)
This thesis identifies how the printing conditions for a high-resolution additive manufacturing technique, melt electrowriting (MEW), needs to be adjusted to process electroactive polymers (EAPs) into microfibers. Using EAPs based on poly(vinylidene difluoride) (PVDF), their ability to be MEW-processed is studied and expands the list of processable materials for this technology.
Biofabrication is an advancing new research field that might, one day, lead to complex products like tissue replacements or tissue analogues for drug testing. Although great progress was made during the last years, there are still major hurdles like new types of materials and advanced processing techniques. The main focus of this thesis was to help overcoming this hurdles by challenging and improving existing fabrication processes like extrusion-based bioprinting but also by developing new techniques. Furthermore, this thesis assisted in designing and processing materials from novel building blocks like recombinant spider silk proteins or inks loaded with charged nanoparticles.
A novel 3D printing technique called Melt Electrospinning Writing (MEW) was used in Chapter 3 to create tubular constructs from thin polymer fibers (roughly 12 μm in diameter) by collecting the fibers onto rotating and translating cylinders. The main focus was put on the influence of the collector diameter and its rotation and translation on the morphology of the constructs generated by this approach. In a first step, the collector was not moving and the pattern generated by these settings was analyzed. It could be shown that the diameter of the stationary collectors had a big impact on the morphology of the constructs. The bigger the diameter of the mandrel (smallest collector diameters 0.5 mm, biggest 4.8 mm) got, the more the shape of the generated footprint converged into a circular one known from flat collectors. In a second set of experiments the mandrels were only rotated. Increasing the rotational velocity from 4.2 to 42.0 rpm transformed the morphology of the constructs from a figure-of-eight pattern to a sinusoidal and ultimately to a straight fiber morphology. It was possible to prove that the transformation of the pattern was comparable to what was known from increasing the speed using flat collectors and that at a critical speed, the so called critical translation speed, straight fibers would appear that were precisely stacking on top of each other. By combining rotation and translation of the mandrel, it was possible to print tubular constructs with defined winding angles. Using collections speeds close to the critical translation speed enabled higher control of fiber positioning and it was possible to generate precisely stacked constructs with winding angles between 5 and 60°.
In Chapter 4 a different approach was followed. It was based on extrusion-based bioprinting in combination with a hydrogel ink system. The ink was loaded with nanoparticles and the nanoparticle release was analyzed. In other words, two systems, a printable polyglycidol/hyaluronic acid ink and mesoporous silica nanoparticles (MSN), were combined to analyze charge driven release mechanism that could be fine-tuned using bioprinting. Thorough rheological evaluations proved that the charged nanoparticles, both negatively charged MSN-COOH and positively charged MSN-NH2, did not alter the shear thinning properties of the ink that revealed a negative base charge due to hyaluronic acid as one of its main components. Furthermore, it could be shown that the particles did also not have a negative effect on the recovery properties of the material after exposure to high shear. During printing, the observations made via rheological testing were supported by the fact that all materials could be printed at the same settings of the bioprinter. Using theses inks, it was possible to make constructs as big as 12x12x3 mm3 composed of 16 layers. The fiber diameters produced were about 627±31 μm and two-component constructs could be realized utilizing the two hydrogel print heads of the printer to fabricate one hybrid construct. The particle distribution within those constructs was homogeneous, both from a microscopic and a macroscopic point of view. Particle release from printed constructs was tracked over 6 weeks and revealed that the print geometry had an influence on the particle release. Printed in a geometry with direct contact between the strands containing different MSN, the positively charged particles quickly migrated into the strand previously containing only negatively charged MSN-COOH. The MSN-COOH seemed to be rather released into the surrounding liquid and also after 6 weeks no MSN-COOH signal could be detected in the strand previously only containing MSN-NH2. In case of a geometry without direct contact between the strands, the migration of the positively charged nanoparticles into the MSN-COOH containing strand was strongly delayed. This proved that the architecture of the printed construct can be used to fine-tune the particle release from nanoparticle containing printable hydrogel ink systems.
Chapter 5 discusses an approach using hydrogel inks based on recombinant spider silk proteins processed via extrusion-based bioprinting. The ink could be applied for printing at protein concentrations of 3 % w/v without the addition of thickeners or any post process crosslinking. Both, the recombinant protein eADF4(C16) and a modification introducing a RGD-sequence to the protein (eADF4(C16)-RGD), could be printed revealing a very good print fidelity. The RGD modification had positive effect on the adhesion of cells seeded onto printed constructs. Furthermore, human fibroblasts encapsulated in the ink at concentrations of 1.2 million cells per mL did not alter the print fidelity and did not interfere with the crosslinking mechanism of the ink. This enabled printing cell laden constructs with a cell survival rate of 70.1±7.6 %. Although the cell survival rate needs to be improved in further trials, the approach shown is one of the first leading towards the shift of the window of biofabrication because it is based on a new material that does not need potentially harmful post-process crosslinking and allows the direct encapsulation of cells staying viable throughout the print process.