@phdthesis{Gensler2023,
  author    = {Gensler, Marius E.},
  title     = {Simultaneous printing of tissue and customized bioreactor},
  doi       = {10.25972/OPUS-28019},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280190},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {Additive manufacturing processes such as 3D printing are booming in the industry due to their high degree of freedom in terms of geometric shapes and available materials. Focusing on patient-specific medicine, 3D printing has also proven useful in the Life Sciences, where it exploits the shape fidelity for individualized tissues in the field of bioprinting. In parallel, the current systems of bioreactor technology have adapted to the new manufacturing technology as well and 3D-printed bioreactors are increasingly being developed. For the first time, this work combines the manufacturing of the tissue and a tailored bioreactor, significantly streamlining the overall process and optimally merging the two processes. This way the production of the tissues can be individualized by customizing the reactor to the tissue and the patient-specific wound geometry. For this reason, a common basis and guideline for the cross-device and cross-material use of 3D printers was created initially. Their applicability was demonstrated by the iterative development of a perfusable bioreactor system, made from polydimethylsiloxane (PDMS) and a lignin-based filament, into which a biological tissue of flexible shape can be bioprinted. Cost-effective bioink-replacements and in silico computational fluid dynamics simulations were used for material sustainability and shape development. Also, nutrient distribution and shear stress could be predicted in this way pre-experimentally. As a proof of functionality and adaptability of the reactor, tissues made from a nanocellulose-based Cellink® Bioink, as well as an alginate-based ink mixed with Me-PMeOx100-b-PnPrOzi100-EIP (POx) (Alginate-POx bioink) were successfully cultured dynamically in the bioreactor together with C2C12 cell line. Tissue maturation was further demonstrated using hMSC which were successfully induced to adipocyte differentiation. For further standardization, a mobile electrical device for automated media exchange was developed, improving handling in the laboratory and thus reduces the probability of contamination.},
  subject      = {3 D bioprinting},
  language  = {en}
}
@phdthesis{Beudert2024,
  author    = {Beudert, Matthias},
  title     = {Bioinspired Modification and Functionalization of Hydrogels for Applications in Biomedicine},
  doi       = {10.25972/OPUS-32288},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-322887},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Over the years, hydrogels have been developed and used for a huge variety of different applications ranging from drug delivery devices to medical products. In this thesis, a poly(2-methyl-2-oxazoline) (POx) / poly(2-n-propyl-2-oxazine) (POzi) bioink was modified and analyzed for the use in biofabrication and targeted drug delivery. In addition, the protein fibrinogen (Fbg) was genetically modified for an increased stability towards plasmin degradation for its use as wound sealant. In Chapter 1, a thermogelling, printable POx/POzi-based hydrogel was modified with furan and maleimide moieties in the hydrophilic polymer backbone facilitating post-printing maturation of the constructs via Diels-Alder chemistry. The modification enabled long-term stability of the hydrogel scaffolds in aqueous solutions which is necessary for applications in biofabrication or tissue engineering. Furthermore, we incorporated RGD-peptides into the hydrogel which led to cell adhesion and elongated morphology of fibroblast cells seeded on top of the scaffolds. Additional printing experiments demonstrate that the presented POx/POzi system is a promising platform for the use as a bioink in biofabrication. Chapter 2 highlights the versatility of the POx/POzi hydrogels by adapting the system to a use in targeted drug delivery. We used a bioinspired approach for a bioorthogonal conjugation of insulin-like growth factor I (IGF-I) to the polymer using an omega-chain-end dibenzocyclooctyne (DBCO) modification and a matrix metalloprotease-sensitive peptide linker. This approach enabled a bioresponsive release of IGF-I from hydrogels as well as spatial control over the protein distribution in 3D printed constructs which makes the system a candidate for the use in personalized medicine. Chapter 3 gives a general overview over the necessity of wound sealants and the current generations of fibrin sealants on the market including advantages and challenges. Furthermore, it highlights trends and potential new strategies to tackle current problems and broadens the toolbox for future generations of fibrin sealants. Chapter 4 applies the concepts of recombinant protein expression and molecular engineering to a novel generation of fibrin sealants. In a proof-of-concept study, we developed a new recombinant fibrinogen (rFbg) expression protocol and a Fbg mutant that is less susceptible to plasmin degradation. Targeted lysine of plasmin cleavage sites in Fbg were exchanged with alanine or histidine in different parts of the molecule. The protein was recombinantly produced and restricted plasmin digest was analyzed using high resolution mass spectrometry. In addition to that, we developed a novel time resolved screening protocol for the detection of new potential plasmin cleavage sites for further amino acid exchanges in the fibrin sealant.},
  subject      = {Hydrogel},
  language  = {en}
}