@phdthesis{Bakirci2024,
  author    = {Bakirci, Ezgi},
  title     = {Development of \(In\) \(vitro\) Models for Tissue Engineering Applications Using a High-Resolution 3D Printing Technology},
  doi       = {10.25972/OPUS-25164},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-251645},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {In vitro models mimic the tissue-specific anatomy and play essential roles in personalized medicine and disease treatments. As a sophisticated manufacturing technology, 3D printing overcomes the limitations of traditional technologies and provides an excellent potential for developing in vitro models to mimic native tissue. This thesis aims to investigate the potential of a high-resolution 3D printing technology, melt electrowriting (MEW), for fabricating in vitro models. MEW has a distinct capacity for depositing micron size fibers with a defined design. In this thesis, three approaches were used, including 1) extending the MEW polymer library for different biomedical applications, 2) developing in vitro models for evaluation of cell growth and migration toward the different matrices, and 3) studying the effect of scaffold designs and biochemical cues of microenvironments on cells. First, we introduce the MEW processability of (AB)n and (ABAC)n segmented copolymers, which have thermally reversible network formulation based on physical crosslinks. Bisurea segments are combined with hydrophobic poly(dimethylsiloxane) (PDMS) or hydrophilic poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) (PPO-PEG-PPO) segments to form the (AB)n segmented copolymers. (ABAC)n segmented copolymers contain all three segments: in addition to bisurea, both hydrophobic and hydrophilic segments are available in the same polymer chain, resulting in tunable mechanical and biological behaviors. MEW copolymers either support cells attachment or dissolve without cytotoxic side effects when in contact with the polymers at lower concentrations, indicating that this copolymer class has potential in biological applications. The unique biological and surface properties, transparency, adjustable hydrophilicity of these copolymers could be beneficial in several in vitro models. The second manuscript addresses the design and development of a melt electrowritten competitive 3D radial migration device. The approach differs from most of the previous literature, as MEW is not used here to produce cell invasive scaffolds but to fabricate an in vitro device. The device is utilized to systematically determine the matrix which promotes cell migration and growth of glioblastoma cells. The glioblastoma cell migration is tested on four different Matrigel concentrations using a melt electrowritten radial device. The glioblastoma U87 cell growth and migration increase at Matrigel concentrations 6 and 8 mg mL-1 In the development of this radial device, the accuracy, and precision of melt electrowritten circular shapes were investigated. The results show that the printing speed and design diameter are essential parameters for the accuracy of printed constructs. It is the first instance where MEW is used for the production of in vitro devices. The influence of biochemical cues and scaffold designs on astrocytes and glioblastoma is investigated in the last manuscript. A fiber comprising the box and triangle-shaped pores within MEW scaffolds are modified with biochemical cues, including RGD and IKVAV peptides using a reactive NCO-sP(EO-stat-PO) macromer. The results show that astrocytes and glioblastoma cells exhibit different phenotypes on scaffold designs and peptide-coated scaffolds.},
  subject      = {3D-Druck},
  language  = {en}
}
@phdthesis{Hauptstein2022,
  author    = {Hauptstein, Julia},
  title     = {Hyaluronic Acid-based Multifunctional Bioinks for 3D Bioprinting of Mesenchymal Stromal Cells for Cartilage Regeneration},
  doi       = {10.25972/OPUS-26068},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260681},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Articular cartilage is a highly specialized tissue which provides a lubricated gliding surface in joints and thereby enables low-friction movement. If damaged once it has a very low intrinsic healing capacity and there is still no treatment in the clinic which can restore healthy cartilage tissue. 3D biofabrication presents a promising perspective in the field by combining healthy cells and bioactive ink materials. Thereby, the composition of the applied bioink is crucial for defect restoration, as it needs to have the physical properties for the fabrication process and also suitable chemical cues to provide a supportive environment for embedded cells. In the last years, ink compositions with high polymer contents and crosslink densities were frequently used to provide 3D printability and construct stability. But these dense polymeric networks were often associated with restricted bioactivity and impaired cell processes like differentiation and the distribution of newly produced extracellular matrix (ECM), which is especially important in the field of cartilage engineering. Therefore, the aim of this thesis was the development of hyaluronic acid (HA)-based bioinks with a reduced polymer content which are 3D printable and additionally facilitate chondrogenic differentiation of mesenchymal stromal cells (MSCs) and the homogeneous distribution of newly produced ECM. Starting from not-printable hydrogels with high polymer contents and restricted bioactivity, distinct stepwise improvements were achieved regarding stand-alone 3D printability as well as MSC differentiation and homogeneous ECM distribution. All newly developed inks in this thesis made a valuable contribution in the field of cartilage regeneration and represent promising approaches for potential clinical applications. The underlying mechanisms and established ink design criteria can further be applied to other biofabricated tissues, emphasizing their importance also in a more general research setting.},
  subject      = {Hyalurons{\"a}ure},
  language  = {en}
}
@phdthesis{Juengst2019,
  author    = {J{\"u}ngst, Tomasz},
  title     = {Establishing and Improving Methods for Biofabrication},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173444},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Die Biofabrikation ist ein junges und sehr dynamisches Forschungsgebiet mit viel Potential. Dieses Potential spiegelt sich unter anderem in den ambitionierten Zielen wieder, die man sich hier gesetzt hat. Wissenschaftler in diesem Gebiet wollen eines Tages beispielsweise funktionale menschliche Gewebe nachbilden, die aus patienteneigenen Zellen bestehen. Diese Gewebe sollen entweder f{\"u}r die Testung neuer Arzneimittel und Therapien oder sogar als Implantate einsetzt werden. Der Schl{\"u}ssel zum Erfolg soll hier die Verwendung automatisierter Prozesse in Verbindung mit innovativen Materialien sein, die es erm{\"o}glichen, die Hierarchie und Funktion des zu ersetzenden nat{\"u}rlichen Gewebes nachbilden. Obwohl in den letzten Jahren große Fortschritte gemacht worden sind, gibt es immer noch H{\"u}rden, die {\"u}berwunden werden m{\"u}ssen. Ziel dieser Arbeit war es deshalb, die derzeit eingeschr{\"a}nkte Auswahl kompatibler Materialien f{\"u}r die Biofabrikation zu erweitern und bereits etablierte Verfahren wie den extrusionsbasierten Biodruck noch besser verstehen zu lernen. Auch neue Verfahren, wie etwa das Melt Electrospinning Writing (MEW) sollten etabliert werden. In Kapitel 3 dieser Arbeit wurde das MEW dazu verwendet, tubul{\"a}re Strukturen zu fertigen, die sich aus Polymerfasern mit einem durchschnittlichen Durchmesser von nur etwa 12 μm zusammensetzen. Die mit Hilfe von Druckluft in Verbindung mit einer hohen elektrischen Spannung aus einer Nadelspitze austretende Polymerschmelze wurde hierbei auf zylinderf{\"o}rmigen Kollektoren mit Durchmessern zwischen 0.5 und 4.8mm gesammelt. Auf diese Weise wurden r{\"o}hrenf{\"o}rmige Faserkonstrukte generiert. Das Hauptaugenmerk lag auf dem Einfluss des Durchmessers, der Rotations- und Translationsbewegung des Kollektors auf die Morphologie der Faserkonstrukte. Hierzu wurden die Fasern erst auf unbewegten Kollektoren mit unterschiedlichen Durchmessern gesammelt und die entstehenden Muster analysiert. Es zeigte sich, dass das Fasermuster mit zunehmendem Durchmesser des Kollektors mehr den symmetrischen Konstrukten mit runder Grundfl{\"a}che glich, die auch von flachen Kollektoren bekannt sind. Je kleiner der Kollektordurchmesser wurde, desto ovaler wurde die Grundfl{\"a}che der Muster, was den Einfluss der Kr{\"u}mmung deutlich machte. In weiteren Experimenten wurden die zylindrischen Kollektoren mit Geschwindigkeiten von 4,2 bis 42 Umdrehungen pro Minute um ihre L{\"a}ngsachse gedreht. Die von flachen Kollektoren bekannten {\"U}berg{\"a}nge der Fasermorphologie konnten auch f{\"u}r runde Kollektoren best{\"a}tigt werden. So {\"a}nderte sich die Morphologie mit zunehmender Geschwindigkeit der Oberfl{\"a}che von einer achterf{\"o}rmigen Gestalt {\"u}ber eine sinusf{\"o}rmige Ausrichtung der Fasern hin zu einer geraden Linie. Der Einfluss des Kollektordurchmessers wurde auch hier deutlich, da sich etwa die Amplitude der bei Rotationsgeschwindigkeiten im Bereich sinusf{\"o}rmiger Ausrichtung abgelegten Fasern mit abnehmendem Radius erh{\"o}hte. Im n{\"a}chsten Schritt wurde neben der Rotation der Kollektoren auch eine Translation induziert. Durch geeignete Kombination von Rotation und Translation konnten Konstrukte mit definiertem Wickelwinkel hergestellt werden. Es zeigte sich, dass die Wiedergabe des vorher kalkulierten Winkels unter Verwendung von Oberfl{\"a}chengeschwindigkeiten, die nahe am {\"U}bergang zur geraden Faserausrichtung waren, am besten war. Im Rahmen dieser Arbeit konnten Winkel zwischen 5 und 60° mit hoher Pr{\"a}zision wiedergegeben werden. Im Falle von sich wiederholenden Mustern konnte auch in Bezug auf die Stapelbarkeit der Fasern aufeinander eine hohe Pr{\"a}zision erreicht werden. Kapitel 4 dieser Arbeit befasste sich mit dem extrusionsbasierten 3D-Druck. Das etabliere Verfahren wurde auf eine bisher wenig untersuchte Materialzusammensetzung von Nanopartikeln-beladenen Hydrogeltinten ausgeweitet. Die Tinte bestand aus einer Kombination von funktionalisierten Polyglyzidolen und einer unmodifizierten langkettingen Hyalurons{\"a}ure. Dieser wurden mesopor{\"o}se Silika-Nanopartikel mit unterschiedlicher Ladung zugesetzt und deren Freisetzung aus gedruckten Konstrukten mit einstellbarer Geometrien untersucht. Da die Hyalurons{\"a}ure selbst negativ geladen ist, wurde erwartet und auch gezeigt, dass aminofunktionalisierte Partikel mit positiver Ladung langsamer freigesetzt werden als carboxylfunktionalisierte Partikel mit negativer Ladung. Interessanterweise {\"a}nderten die Partikel nicht die rheologischen Eigenschaften der Tinte und es konnten Hydrogele, die mit positiv geladenen Partikeln beladen waren, bei den gleichen Druckparametern verdruckt werden, wie Hydrogele, die mit negativ geladenen Partikeln beladen waren. Die guten Druckeigenschaften der Tinten erm{\"o}glichten die pr{\"a}zise Fertigung von Konstrukten mit einer Gr{\"o}ße von 12x12x3mm^3, also von Konstrukten mit bis zu 16 aufeinanderfolgenden Lagen. Die Strangdurchmesser betrugen hierbei 627±31μm und die Verteilung der Partikel innerhalb der Str{\"a}nge war sehr homogen. Zudem konnten auch Strukturen gedruckt werden, bei denen beide Tintenarten, mit positiven und mit negativen Partikeln beladene Hydrogele, in einem Konstrukt kombiniert wurden. Hierbei zeigte sich, dass die Freisetzung der Partikel, die {\"u}ber 6 Wochen hinweg untersucht wurde, auch stark von der Geometrie der zwei-Komponenten-Konstrukte abhing. Insbesondere die Auswirkung des direkten Kontakts zwischen den Komponenten innerhalb eines Konstruktes war hier sehr deutlich. Wurden die Str{\"a}nge {\"u}ber Kreuz aufeinander abgelegt und hatten direkten Kontakt an den Kreuzungspunkten, konnte beobachtet werden, dass die positiv geladenen Partikel aus ihrem System in das mit den negativ geladenen Partikeln wanderten. Wurden die Str{\"a}nge ohne direkten Kontakt parallel nebeneinander abgelegt, wurden die positiv geladenen Partikel in umgebendes Medium freigesetzt, konnten aber selbst nach 6 Wochen nicht in den Str{\"a}ngen mit den negativ geladenen Partikeln nachgewiesen werden. Dies verdeutlicht, dass Geometrie und Ladung der Partikel einen Einfluss auf die Freisetzung der Partikel hatten und sich die Freisetzung der Partikel durch eine geschickte Kombination beider Parameter steuern l{\"a}sst. In Kapitel 5 dieser Arbeit wurde eine neue Materialklasse als Biotinte f{\"u}r den extrusionsbasierten Biodruck untersucht. Bei dem Material handelte es sich um Hydrogele auf Basis rekombinanter Spinnenseidenproteine. Diese konnten ab einer Proteinkonzentration von 3 \%Gew./Vol. ohne die Verwendung von Verdickungsmittel oder anderen Additiven und auch ohne eine nachtr{\"a}gliche Vernetzung verdruckt werden. Sowohl Hydrogele auf Basis des rekombinanten Proteins eADF4(C16) als auch eine mit einer RGD-Sequenz versehene Modifikation (eADF4(C16)-RGD) konnten mit einer hohen Formtreue verdruckt werden. Die RGD-Sequenz zeigte einen positiven Effekt auf das Anhaften von humanen Fibroblasten, die auf gedruckte Konstrukte ausges{\"a}t wurden. Zudem konnten mit Hilfe der Hydrogele auch zellbeladene Konstrukte gefertigt werden. Hierzu wurden die Hydrogele mit einer Zellsuspension so vermengt, dass eine finale Konzentration von 1,2 Millionen Zellen/ml erreicht wurde. Die beladenen Gele wurden verdruckt und es konnte eine {\"U}berlebensrate von 70,1±7,6\% nachgewiesen werden. Das in diesem Kapitel etablierte Materialsystem erm{\"o}glichte zum ersten Mal das Verdrucken lebender Zellen in einer neuen Klasse von Tinten, die weder die Beimengung von Verdickungsmittel noch einen zus{\"a}tzlichen Nachh{\"a}rtungsschritt f{\"u}r die Herstellung zellbeladener stabiler Konstrukte ben{\"o}tigt.},
  subject      = {3D-Druck},
  language  = {en}
}
@phdthesis{Kade2023,
  author    = {Kade, Juliane Carolin},
  title     = {Expanding the Processability of Polymers for a High-Resolution 3D Printing Technology},
  doi       = {10.25972/OPUS-27005},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270057},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {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.},
  subject      = {Polymere},
  language  = {en}
}
@phdthesis{Lorson2019,
  author    = {Lorson, Thomas},
  title     = {Novel Poly(2-oxazoline) Based Bioinks},
  doi       = {10.25972/OPUS-18051},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180514},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Motivated by the great potential which is offered by the combination of additive manufacturing and tissue engineering, a novel polymeric bioink platform based on poly(2 oxazoline)s was developed which might help to further advance the young and upcoming field of biofabrication. In the present thesis, the synthesis as well as the characteristics of several diblock copolymers consisting of POx and POzi have been investigated with a special focus on their suitability as bioinks. In general, the copolymerization of 2-oxazolines and 2-oxazines bearing different alkyl side chains was demonstrated to yield polymers in good agreement with the degree of polymerization aimed for and moderate to low dispersities. For every diblock copolymer synthesized during the present study, a more or less pronounced dependency of the dynamic viscosity on temperature could be demonstrated. Diblock copolymers comprising a hydrophilic PMeOx block and a thermoresponsive PnPrOzi block showed temperature induced gelation above a degree of polymerization of 50 and a polymer concentration of 20 wt\%. Such a behavior has never been described before for copolymers solely consisting of poly(cyclic imino ether)s. Physically cross linked hydrogels based on POx b POzi copolymers exhibit reverse thermal gelation properties like described for solutions of PNiPAAm and Pluronic F127. However, by applying SANS, DLS, and SLS it could be demonstrated that the underlying gel formation mechanism is different for POx b POzi based hydrogels. It appears that polymersomes with low polydispersity are formed already at very low polymer concentrations of 6 mg/L. Increasing the polymer concentration resulted in the formation of a bicontinuous sponge like structure which might be formed due to the merger of several vesicles. For longer polymer chains a phase transition into a gyroid structure was postulated and corresponds well with the observed rheological data. Stable hydrogels with an unusually high mechanical strength (G' ~ 4 kPa) have been formed above TGel which could be adjusted over a range of 20 °C by changing the degree of polymerization if maintaining the symmetric polymer architecture. Variations of the chain ends revealed only a minor influence on TGel whereas the influence of the solvent should not be neglected as shown by a comparison of cell culture medium and MilliQ water. Rotationally as well as oscillatory rheological measurements revealed a high suitability for printing as POx b POzi based hydrogels exhibit strong shear thinning behavior in combination with outstanding recovery properties after high shear stress. Cell viability assays (WST-1) of PMeOx b PnPrOzi copolymers against NIH 3T3 fibroblasts and HaCat cells indicated that the polymers were well tolerated by the cells as no dose-dependent cytotoxicity could be observed after 24 h at non-gelling concentrations up to 100 g/L. In summary, copolymers consisting of POx and POzi significantly increased the accessible range of properties of POx based materials. In particular thermogelation of aqueous solutions of diblock copolymers comprising PMeOx and PnPrOzi was never described before for any copolymer consisting solely of POx or POzi. In combination with other characteristics, e.g. very good cytocompatibility at high polymer concentrations and comparably high mechanical strength, the formed hydrogels could be successfully used for 3D bioprinting. Although the results appear promising and the developed hydrogel is a serious bioink candidate, competition is tough and it remains an open question which system or systems will be used in the future.},
  subject      = {Polymere},
  language  = {en}
}
@phdthesis{Nadernezhad2024,
  author    = {Nadernezhad, Ali},
  title     = {Engineering approaches in biofabrication of vascularized structures},
  doi       = {10.25972/OPUS-34589},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-345892},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Biofabrication technologies must address numerous parameters and conditions to reconstruct tissue complexity in vitro. A critical challenge is vascularization, especially for large constructs exceeding diffusion limits. This requires the creation of artificial vascular structures, a task demanding the convergence and integration of multiple engineering approaches. This doctoral dissertation aims to achieve two primary objectives: firstly, to implement and refine engineering methods for creating artificial microvascular structures using Melt Electrowriting (MEW)-assisted sacrificial templating, and secondly, to deepen the understanding of the critical factors influencing the printability of bioink formulations in 3D extrusion bioprinting. In the first part of this dissertation, two innovative sacrificial templating techniques using MEW are explored. Utilizing a carbohydrate glass as a fugitive material, a pioneering advancement in the processing of sugars with MEW with a resolution under 100 microns was made. Furthermore, by introducing the "print-and-fuse" strategy as a groundbreaking method, biomimetic branching microchannels embedded in hydrogel matrices were fabricated, which can then be endothelialized to mirror in vivo vascular conditions. The second part of the dissertation explores extrusion bioprinting. By introducing a simple binary bioink formulation, the correlation between physical properties and printability was showcased. In the next step, employing state-of-the-art machine-learning approaches revealed a deeper understanding of the correlations between bioink properties and printability in an extended library of hydrogel formulations. This dissertation offers in-depth insights into two key biofabrication technologies. Future work could merge these into hybrid methods for the fabrication of vascularized constructs, combining MEW's precision with fine-tuned bioink properties in automated extrusion bioprinting.},
  subject      = {3D-Druck},
  language  = {en}
}
@phdthesis{Nahm2021,
  author    = {Nahm, Daniel},
  title     = {Poly(2-oxazine) Based Biomaterial Inks for the Additive Manufacturing of Microperiodic Hydrogel Scaffolds},
  doi       = {10.25972/OPUS-24598},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245987},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {The aim of this thesis was the preparation of a biomaterial ink for the fabrication of chemically crosslinked hydrogel scaffolds with low micron sized features using melt electrowriting (MEW). By developing a functional polymeric material based on 2-alkyl-2-oxazine (Ozi) and 2-alkyl-2-oxazoline (Ox) homo- and copolymers in combination with Diels-Alder (DA)-based dynamic covalent chemistry, it was possible to achieve this goal. This marks an important step for the additive manufacturing technique melt electrowriting (MEW), as soft and hydrophilic structures become available for the first time. The use of dynamic covalent chemistry is a very elegant and efficient method for consolidating covalent crosslinking with melt processing. It was shown that the high chemical versatility of the Ox and Ozi chemistry offers great potential to control the processing parameters. The established platform offers straight forward potential for modification with biological cues and fluorescent markers. This is essential for advanced biological applications. The physical properties of the material are readily controlled and the potential for 4D-printing was highlighted as well. The developed hydrogel architectures are excellent candidates for 3D cell culture applications. In particular, the low internal strength of some of the scaffolds in combination with the tendency of such constructs to collapse into thin strings could be interesting for the cultivation of muscle or nerve cells. In this context it was also possible to show that MEW printed hydrogel scaffolds can withstand the aspiration and ejection through a cannula. This allows the application as scaffolds for the minimally invasive delivery of implants or functional tissue equivalent structures to various locations in the human body.},
  subject      = {Polymere},
  language  = {en}
}
@phdthesis{Ryma2022,
  author    = {Ryma, Matthias},
  title     = {Exploiting the Thermoresponsive Properties of Poly(2-oxazoline)s for Biofabrication},
  doi       = {10.25972/OPUS-24746},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-247462},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {In this thesis, non-modified POx, namely PnPrOx and PcycloPrOx, with an LCST in the physiological range between 20 and 37°C have been utilized as materials for three different biofabrication approaches. Their thermoresponsive behavior and processability were exploited to establish an easy-to-apply coating for cell sheet engineering, a novel method to create biomimetic scaffolds based on aligned fibrils via Melt Electrowriting (MEW) and the application of melt electrowritten sacrificial scaffolds for microchannel creation for hydrogels. Chapter 3 describes the establishment of a thermoresponsive coating for tissue culture plates. Here, PnPrOx was simply dissolved in water and dried in well plates and petri dishes in an oven. PnPrOx adsorbed to the surface, and the addition of warm media generated a cell culture compatible coating. It was shown that different cell types were able to attach and proliferate. After confluency, temperature reduction led to the detachment of cell sheets. Compared to standard procedures for surface coating, the thermoresponsive polymer is not bound covalently to the surface and therefore does not require specialized equipment and chemical knowledge. However, it should be noted that the detachment of the cell layer requires the dissolution of the PnPrOx-coating, leading to possible polymer contamination. Although it is only a small amount of polymer dissolved in the media, the detached cell sheets need to be washed by media exchange for further processing if required. ...},
  subject      = {Thermoresponsive Polymere},
  language  = {en}
}
@phdthesis{SchaefergebStichler2019,
  author    = {Sch{\"a}fer [geb. Stichler], Simone},
  title     = {Thiol-ene Cross-linked Poly(glycidol) / Hyaluronic Acid Based Hydrogels for 3D Bioprinting},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-174713},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {The aim of the work was the development of thiol-ene cross-linked hydrogels based on functionalized poly(glycidol)s (PG) and hyaluronic acid (HA) for extrusion based 3D bioprinting. Additionally, the functionalization of the synthesized PG with peptides and the suitability of these polymers for physically cross-linked gels were investigated, in a proof of principle study in order to demonstrate the versatile use of PG polymers in hydrogel development. First, the precursor polymers of the different hydrogel systems were synthesized. For thiol-ene cross-linked hydogels, linear allyl-functionalized PG (P(AGE-co-G)) and three different thiol-(SH-)functionalized polymers, ester-containing PG-SH (PG SHec), ester-free PG-SH (PG-SHef) and HA-SH were synthesized and analysed, The degree of functionalization of these polymers was adjustable. For physically cross-linked hydrogels, peptide-functionalized PG (P(peptide-co-G)), was synthesized through polymer analogue thiol-ene modification of P(AGE-co-G). Subsequently, thiol-ene cross-linked hydrogels were prepared with the synthesized thiol- and allyl-functionalized polymers. Depending on the origin of the used polymers, two different systems were obtained: on the one hand synthetic hydrogels consisting of PG-SHec/ef and P(AGE-co-G) and on the other hand hybrid gels, consisting of HA-SH and P(AGE-co-G). In synthetic gels, the degradability of the gels was determined by the applied PG-SH. The use of PG-SHec resulted in hydrolytically degradable hydrogels, whereas the cross-linking with PG-SHef resulted in non-degradable gels. The physical properties of these different hydrogel systems were determined by swelling, mechanical and diffusion studies and subsequently compared among each other. In swelling studies the differences of degradable and non-degradable synthetic hydrogels as well as the differences of synthetic compared to hybrid hydrogels were demonstrated. Next, the stiffness and the swelling ratios (SR) of the established hydrogel systems were examined in dependency of different parameters, such as incubation time, polymer concentration and UV irradiation. In general, these measurements revealed the same trends for synthetic and hybrid hydrogels: an increased polymer concentration as well as prolonged UV irradiation led to an increased network density. Moreover, it was demonstrated that the incorporation of additional non-bound HMW HA hampered the hydrogel cross-linking resulting in gels with decreased stiffness and increased SR. This effect was strongly dependent on the amount of additional HMW HA. The diffusion of different molecular weight fluorescein isothiocyanate-dextran (FITC-dextran) through hybrid hydrogels (with/without HMW HA) gave information about the mesh size of these gels. The smallest FITC-dextran (4 kDa) completely diffused through both hydrogel systems within the first week, whereas only 55 \% of 40 kDa and 5-10 \% HMW FITC-dextrans (500 kDa and 2 MDa) could diffuse through the networks. The applicability of synthetic and hybrid hydrogels for cartilage regeneration purpose was investigated through by biological examinations. It was proven that both gels support the survival of embedded human mesenchymal stromal cells (hMSCs) (21/28 d in vitro culture), however, the chondrogenic differentiation was significantly improved in hybrid hydrogels compared to synthetic gels. The addition of non-bound HMW HA resulted in a slightly less distinct chondrogenesis. Lastly the printability of the established hydrogel systems was examined. Therefore, the viscoelastic properties of the hydrogel solutions were adjusted by incorporation of non-bound HMW HA. Both systems could be successfully printed with high resolution and high shape fidelity. The introduction of the double printing approach with reinforcing PCL allowed printing of hydrogel solutions with lower viscosities. As a consequence, the amount of additional HMW HA necessary for printing could be reduced allowing successful printing of hybrid hydrogel solutions with embedded cells. It was demonstrated that the integrated cells survived the printing process with high viability measured after 21 d. Moreover, by this reinforcing technique, robust hydrogel-containing constructs were fabricated. In addition to thiol-ene cross-linked hydrogels, hydrogel cross-linking via ionic interactions was investigated with a hybrid hydrogel based on HMW HA and peptide-functionalized PG. Rheological measurements revealed an increase in the viscosity of a 2 wt.\% HMW HA solution by the addition of peptide-functionalized PG. The increase in viscosity could be attributed to the ionic interactions between the positively charge PG and the negatively charge HMW HA. In conclusion, throughout this thesis thiol-ene chemistry and PG were introduced as promising cross-linking reaction and polymer precursor for the field of biofabrication. Furthermore, the differences of hybrid and synthetic hydrogels as well as chemically and physically cross-linked hydrogels were demonstrated. Moreover, the double printing approach was demonstrated to be a promising tool for the fabrication of robust hydrogel-containing constructs. It opens the possibility of printing hydrogels that were not printable yet, due to too low viscosities.},
  subject      = {Hyalurons{\"a}ure},
  language  = {en}
}