@article{FleglerSchneiderPrieschletal.2016, author = {Flegler, Andreas and Schneider, Michael and Prieschl, Johannes and Stevens, Ralph and Vinnay, Thomas and Mandel, Karl}, title = {Continuous flow synthesis and cleaning of nano layered double hydroxides and the potential of the route to adjust round or platelet nanoparticle morphology}, series = {RSC Advances}, volume = {6}, journal = {RSC Advances}, number = {62}, doi = {10.1039/c6ra09553d}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-191305}, pages = {57236-57244}, year = {2016}, abstract = {Here, we report a continuous flow synthesis of nano LDH, comprising a continuous precipitation process using static mixers and followed by an immediate cleaning process via a semi-continuous centrifuge to obtain the final product in one-go. Via this synthesis setup, it is possible to independently vary the concentrations of the reactants during precipitation and at the same time ensure constant reaction conditions and an immediate "quenching" of the precipitate due to "on the flow"-washing. We found that this paves the way to adjust the synthesis parameters in a way that the final morphology of the nano-LDH particles can be controlled to be either round or platelet-like.}, language = {en} } @article{EmmertWitzelHeinrich2016, author = {Emmert, M. and Witzel, P. and Heinrich, D.}, title = {Challenges in tissue engineering - towards cell control inside artificial scaffolds}, series = {Soft Matter}, volume = {12}, journal = {Soft Matter}, number = {19}, doi = {10.1039/c5sm02844b}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-191341}, pages = {4287-4294}, year = {2016}, abstract = {Control of living cells is vital for the survival of organisms. Each cell inside an organism is exposed to diverse external mechano-chemical cues, all coordinated in a spatio-temporal pattern triggering individual cell functions. This complex interplay between external chemical cues and mechanical 3D environments is translated into intracellular signaling loops. Here, we describe how external mechano-chemical cues control cell functions, especially cell migration, and influence intracellular information transport. In particular, this work focuses on the quantitative analysis of (1) intracellular vesicle transport to understand intracellular state changes in response to external cues, (2) cellular sensing of external chemotactic cues, and (3) the cells' ability to migrate in 3D structured environments, artificially fabricated to mimic the 3D environment of tissue in the human body.}, language = {en} } @phdthesis{Bertlein2019, author = {Bertlein, Sarah}, title = {Hydrogels as Biofunctional Coatings and Thiol-Ene Clickable Bioinks for Biofabrication}, doi = {10.25972/OPUS-17422}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-174225}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Ziel dieser Arbeit war die Entwicklung von funktionalisierbaren Hydrogel Beschichtungen f{\"u}r Schmelz-elektrogeschriebene PCL Ger{\"u}ste und von Bio-druckbaren Hydrogelen f{\"u}r die Biofabrikation. Hydrogel Beschichtungen von Schmelz-elektrogeschriebenen Konstrukten erm{\"o}glichten die Kontrolle der Oberfl{\"a}chen-Hydrophilie und damit Zell-Material Interaktionsstudien in minimal Protein-adh{\"a}siven Umgebungen. Zu diesem Zweck wurde ein hydrophiles sternf{\"o}rmiges vernetzbares Polymer verwendet und eine Optimierung der Beschichtungsbedingungen durchgef{\"u}hrt. Außerdem boten neu entwickelte photosensitive Konstrukte eine Zeit- und pH-unabh{\"a}ngige Biofunktionalisierung. Bio-druckbare Hydrogele f{\"u}r die Biofabrikation basierten auf der Allyl-Funktionalisierung von Gelatine (GelAGE) und modifizierten Hyalurons{\"a}ure-Produkten, die das Hydrogel-Vernetzen mittels Thiol-En Click Chemie erm{\"o}glichen. Die Optimierung der GelAGE Hydrogel-Eigenschaften wurde durch eine detaillierte Analyse der Syntheseparameter, variierender En:SH Verh{\"a}ltnisse, unterschiedlicher Vernetzungsmolek{\"u}le und Photoinitiatoren erreicht. Die Homogenit{\"a}t der Thiol-En Netzwerke wurde mit denen der freien radikalischen Polymerisation verglichen und die Verwendbarkeit von GelAGE als Bio-Tinte f{\"u}r den Extrusions-basierten Bio-Druck wurde untersucht. Es wurde angenommen, dass reine Hyalurons{\"a}ure-basierte Bio-Tinten eine Beibehaltung der mechanischen und rheologischen Eigenschaften, der Zellviabilit{\"a}t und der Prozessierbarkeit erm{\"o}glichen trotz geringerem Polymer- und Thiol-Anteil der Hydrogele. Hydrogel-Beschichtungen: Hoch definierte PCL Ger{\"u}ste wurden mittels MEW hergestellt und anschließend mit sechs armigen sternf{\"o}rmigen vernetzbaren Polymeren (sP(EO-stat-PO)) beschichtet. Die Vernetzung wird durch die w{\"a}ssrig-induzierte Hydrolyse reaktiver Isocyanatgruppen (NCO) von sP(EO-stat-PO) bedingt. Diese Beschichtung erh{\"o}hte die Oberfl{\"a}chen-Hydrophilie und stellte eine Plattform f{\"u}r weitere Biofunktionalisierungen, in minimal Protein-adh{\"a}siven Umgebungen, dar. Nicht nur das Beschichtungsprotokoll wurde hinsichtlich der sP(EO-stat-PO) Konzentrationen und der Beschichtungsdauern optimiert, sondern auch Vorbehandlungen der Ger{\"u}ste wurden entwickelt. Diese waren essentiell um die finale Hydrophilie von sP(EO-stat-PO) beschichteten Ger{\"u}ste so zu erh{\"o}hen, dass unspezifische Protein-Adh{\"a}sionen vollst{\"a}ndig unterbunden wurden. Die sP(EO-stat-PO) Schichtdicke, von ungef{\"a}hr 100 nm, erm{\"o}glicht generell in vitro Studien nicht nur in Abh{\"a}ngigkeit der Ger{\"u}st-Biofunktionalisierung, sondern auch in Abh{\"a}ngigkeit der Ger{\"u}st-Architektur durchzuf{\"u}hren. Das Ausmaß der Hydrogel-Beschichtung wurde mittels einer indirekten Quantifizierung der NCO-Hydrolyse-Produkte ermittelt. Kenntnis {\"u}ber die NCO-Hydrolyse-Kinetik erm{\"o}glichte ein Gleichgewicht zwischen ausreichend beschichteten Ger{\"u}sten und der Pr{\"a}senz der NCO-Gruppen herzustellen, welche f{\"u}r die anschließenden Biofunktionalisierungen genutzt wurden. Diese Zeit- und pH-abh{\"a}ngige Biofunktionalisierung war jedoch nur f{\"u}r kleine Biomolek{\"u}le m{\"o}glich. Um diese Beschr{\"a}nkung zu umgehen und auch hochmolekulare Biomolek{\"u}le kovalent anzubinden, wurde ein anderer Reaktionsweg entwickelt. Dieser basierte auf der Photolyse von Diazirin-Gruppen und erm{\"o}glichte eine Zeit- und pH-unabh{\"a}ngige Biofunktionalisierung der Ger{\"u}ste mit Streptavidin und Kollagen Typ I. Die Fibrillen bildende Eigenschaft von Kollagen wurde genutzt um auf den Ger{\"u}sten verschiedene Kollagen-Konformationen zu erhalten und eine erste in vitro Studie best{\"a}tigte die Anwendbarkeit f{\"u}r Zell-Material Interaktionsstudien. Die hier entwickelten Ger{\"u}ste k{\"o}nnten verwendet werden um tiefere Einblicke in die Grundlagen der zellul{\"a}ren Wahrnehmung zu erhalten. Insbesondere die Komplexit{\"a}t mit der Zellen z.B. Kollagen wahrnehmen bleibt weiterhin kl{\"a}rungsbed{\"u}rftig. Hierf{\"u}r k{\"o}nnten diverse Hierarchien von Kollagen-{\"a}hnlichen Konformationen an die Ger{\"u}ste gebunden werden, z.B. Gelatine oder Kollagen-abgeleitete Peptidsequenzen. Dann k{\"o}nnte die Aktivierung der DDR-Rezeptoren in Abh{\"a}ngigkeit der Komplexit{\"a}t der angebundenen Substanzen bestimmt werden. Aufgrund der starken Streptavidin-Biotin Bindung k{\"o}nnten Streptavidin funktionalisierte Ger{\"u}ste eine vielseitige Plattform f{\"u}r die Immobilisierung von jeglichen biotinylierten Molek{\"u}len darstellen. Gelatine-basierte Bio-Tinten: Zuerst wurden die GelAGE-Produkte hinsichtlich der Molekulargewichts-Verteilung und der Integrit{\"a}t der Aminos{\"a}uren-Zusammensetzung synthetisiert. Eine detailliert Studie, mit variierenden molaren Edukt-Verh{\"a}ltnissen und Synthese-Zeitspannen, wurde durchgef{\"u}hrt und implizierte, dass der Gelatine Abbau am deutlichsten f{\"u}r stark alkalische Synthesebedingungen mit langen Reaktionszeiten war. Gelatine beinhaltet mehrere funktionalisierbare Gruppen und anhand diverser Model-Substanzen und Analysen wurde die vorrangige Amingruppen-Funktionalisierung ermittelt. Die Homogenit{\"a}t des GelAGE-Polymernetzwerkes, im Vergleich zu frei radikalisch polymerisierten GelMA-Hydrogelen, wurde best{\"a}tigt. Eine ausf{\"u}hrliche Analyse der Hydrogel-Zusammensetzungen mit variierenden funktionellen Gruppen Verh{\"a}ltnissen und UV- oder Vis-Licht induzierbaren Photoinitiatoren wurde durchgef{\"u}hrt. Die UV-Initiator Konzentration ist aufgrund der Zell-Toxizit{\"a}t und der potenziellen zellul{\"a}ren DNA-Besch{\"a}digung durch UV-Bestrahlung eingeschr{\"a}nkt. Das Zell-kompatiblere Vis-Initiator System hingegen erm{\"o}glichte, durch die kontrollierte Photoinitiator-Konzentration bei konstanten En:SH Verh{\"a}ltnissen und Polymeranteilen, die Einstellung der mechanischen Eigenschaften {\"u}ber eine große Spanne hinweg. Die Flexibilit{\"a}t der GelAGE Bio-Tinte f{\"u}r unterschiedliche additive Fertigungstechniken konnte, durch Ausnutzung des temperaturabh{\"a}ngigen Gelierungsverhaltens unterschiedlich stark degradierter GelAGE Produkte, f{\"u}r Stereolithographie und Extrusions-basiertem Druck bewiesen werden. Außerdem wurde die Viabilit{\"a}t zellbeladener GelAGE Konstrukte bewiesen, die mittels Extrusions-basiertem Bio-Druck erhalten wurden. Die Verwendung diverser multifunktioneller und makromolekularer Thiol-Vernetzungsmolek{\"u}le erm{\"o}glichte eine Verbesserung der mechanischen und rheologischen Eigenschaften und ebenso der Prozessierbarkeit. Verglichen mit dem kleinen bis-Thiol-funktionellen Vernetzungsmolek{\"u}l waren geringere Thiol-Vernetzer-Konzentrationen notwendig um bessere mechanische Festigkeiten und physikochemische Eigenschaften der Hydrogele zu erhalten. Der Extrusions-basierte Bio-Druck unterschiedlicher eingekapselter Zellen verdeutlichte die Notwendigkeit der individuellen Optimierung von Zell-beladenen Hydrogel-Formulierungen. Nicht nur die Zellviabilit{\"a}t von eingekapselten Zellen in Extrusions-basierten biogedruckten Konstrukten sollte bewertet werden, sondern auch andere Parameter wie die Zellmorphologie oder die Kollagen- oder Glykosaminoglykan-Produktion, da diese einige der essentiellen Voraussetzungen f{\"u}r die Verwendung in Knorpel Tissue Engineering Konzepten darstellen. Außerdem sollten diese Studien auf die stereolithographischen Ans{\"a}tze erweitert werden und letztlich w{\"a}re die Flexibilit{\"a}t und Zellkompatibilit{\"a}t der Formulierungen mit makromolekularen Vernetzern von Interesse. Makromolekulare Vernetzer erm{\"o}glichten die Reduktion des Polymeranteils und des Thiol-Gehalts und k{\"o}nnen, insbesondere in Kombination mit dem Zell-kompatibleren Vis-Initiator-System, voraussichtlich zu einer gesteigerten Zellkompatibilit{\"a}t beitragen, was zu kl{\"a}ren bleibt. Hyalurons{\"a}ure-basierte Bio-Tinten: Unterschiedliche Hyalurons{\"a}ure-Produkte (HA) wurden synthetisiert, sodass diese En- (HAPA) oder Thiol-Funktionalit{\"a}ten (LHASH) beinhalteten, um reine HA Thiol-En vernetzte Hydrogele zu erhalten. In Abh{\"a}ngigkeit des Molekulargewichts der HA-Produkte, der Polymeranteile und des En:SH Verh{\"a}ltnisses, konnte eine große Spanne an mechanischen Festigkeiten abgedeckt werden. Aufgrund der hohen Viskosit{\"a}t war allerdings im Falle von hochmolekularen HA (HHAPA) Produkt-L{\"o}sungen (HHAPA + LHASH) die Handhabbarkeit auf 5.0 wt.-\% beschr{\"a}nkt. Die Verwendung der gleichen HA Thiol-Komponenten (LHASH) erm{\"o}glichte Hybrid-Hydrogele, mit HA und GelAGE, mit reinen HA-Hydrogelen zu vergleichen. Obwohl der Polymeranteil von HHAPA + LHASH Hydrogelen signifikant geringer war, als im Vergleich zu Hybrid-Hydrogelen (GelAGE + LHASH), wurden f{\"u}r gleiche En:SH Verh{\"a}ltnisse {\"a}hnliche mechanische und physikochemische Eigenschaften reiner HA-Hydrogele bestimmt. Aufgrund der geringen Viskosit{\"a}t niedermolekularer HA L{\"o}sungen (LHAPA + LHASH) konnten diese nicht f{\"u}r den Extrusions-basierten Druck verwendet werden. Das nicht temperaturabh{\"a}ngige HHAPA + LHASH System hingegen konnte mit nur einem Viertel des Polymeranteils der Hybrid Formulierungen gedruckt werden. Im Vergleich zu der Hybrid Bio-Tinte wurde angenommen, dass das hoch viskose Verhalten von HHAPA + LHASH L{\"o}sungen, der geringere Polymeranteil, der geringere Druck f{\"u}r das Drucken und eine demzufolge geringere Scherspannung, maßgeblich zu der hohen Zellviabilit{\"a}t in Extrusions-basiert-biogedruckten Konstrukten beisteuerten. Die niedrigmolekulare HA Formulierung (LHAPA + LHASH) konnte zwar nicht f{\"u}r den Extrusions-basierten Druck verwendet werden, allerdings besitzt dieses System Potential f{\"u}r andere additive Fertigungstechniken wie z.B. der Stereolithographie. Um dieses System weiterzuentwickeln w{\"a}re, analog zu dem GelAGE System, eine detailliertere Studie zu den Funktionen eingekapselter Zellen hilfreich. Außerdem sollte die Initiierung dieses Systems mit dem Vis-Initiator untersucht werden.}, subject = {Biomaterial}, language = {en} } @phdthesis{Declerck2010, author = {Declerck, P{\´e}lagie}, title = {Synthesis and technological processing of hybrid organic-inorganic materials for photonic applications}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-56053}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2010}, abstract = {Im Rahmen dieser Doktorarbeit wurden neue UV-strukturierbare organisch-anorganische hybride Polymere f{\"u}r photonische Anwendungen mit einem hohem Brechungsindex und der M{\"o}glichkeit, sie durch Ein- bzw. Zwei-Photonen-Polymerisation zu strukturieren, entwickelt. Die Materialien wurden in Bezug auf ihre chemische Struktur, ihre optischen Eigenschaften, und ihrer F{\"a}higkeit, durch 1PP und 2PP strukturierbar zu sein, untersucht. Besonders mit 2PP konnte man mit diesen neuartigen hybriden Materialien 3D-Strukturen erzeugen. ie Hydrolyse und Polykondensationsreaktionen wurden mit · Organo-Alkoxysilanen und Titanalkoxiden, modifiziert mit und ohne komplexierende Liganden und · Organo-Alkoxysilanen, Titanalkoxiden und Organophosphors{\"a}ure als Precrusoren durchgef{\"u}hrt. Prim{\"a}res Ziel dieser Arbeit war es, den Brechungsindex von ORMOCER®en, die auf der Basis von Organo-Alkoxysilan-Precursoren ohne Heteroelemente synthetisiert werden, zu vergr{\"o}ßern. Die chemische Struktur der synthetisierten Materialien und somit mit ihr die Parameter, die den Brechungsindex beeinflussen, wurden eingehend untersucht. Insbesondere die Synthese-Parameter, wie das Einsetzen der Titanalkoxide und ihrer Konzentration, der Organo-Alkoxysilane, die Katalysator-Konzentration, die verwendeten L{\"o}sungsmittel und auch die Verfahrensparameter f{\"u}r eine sp{\"a}tere Strukturierung durch lithographische Verfahren, wie die UV-Bestrahlungsdosis, die Initiator-Konzentration und der Entwickler, wurden untersucht.}, subject = {Brechzahl}, language = {en} } @phdthesis{Goetzendoerfer2010, author = {G{\"o}tzend{\"o}rfer, Stefan}, title = {Synthesis of Copper-Based Transparent Conductive Oxides with Delafossite Structure via Sol-Gel Processing}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-51601}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2010}, abstract = {Starting off with solubility experiments of possible precursors, the present study reveals the whole development of a sol gel processing route for transparent p type semiconductive thin films with delafossite structure right to the fabrication of functional p-n junctions. The versatile sol formulation could successfully be modified for several oxide compositions, enabling the synthesis of CuAlO2, CuCrO2, CuMnO2, CuFeO2 and more. Although several differences in the sintering behaviour of powders and thin films could be observed, the powder experiments significantly contributed to the clearification of the intricate phase development during thermal annealing and also to optimization of the annealing sequence for thin film processing. Two different ternary systems turned out to be the most promising candidates for p-TCO application: Copper aluminum oxide for its high optical transmittance and copper chromium oxide for its low synthesis temperature, which allowed thin film deposition on low-cost borosilicate substrates. In order to combine the advantages of these two systems, the quaternary oxide composition CuAl1-xCrxO2 was investigated. With a higher optical transmittance than CuCrO2, a lower synthesis temperature than CuAlO2 and a lower resistivity than both parent systems, the optimum composition of the quaternary oxide is reached for x = 0.50. Compared to physical vapour deposition techniques, the undoped thin films presented here still need to make up some deficites in their optoelectronic performance. Although the best sol-gel samples are able to compete with RF sputtered samples or sampes deposited by PLD in transmittance, their resistivity is almost two orders of magnitude higher. The most probable reasons for this are the characteristic imperfections of sol-gel thin films like porosity and small crystallite size, which create barriers like grain boundaries and bottlenecks like barely connected particles. By additional effort such shortcomings can be repelled to a certain extend, but nevertheless the density of undoped sol-gel material always stays behind its pendants processed by physical vapour deposition.[246] Furthermore, such additional endeavour is likely to annihilate the advantage of sol-gel technique in processing costs. Extrinsic doping is a common method to decrease the resistivity of delafossite materials. Partially replacing the trivalent cations by divalent ones creates additional holes and thus generates additional charge carriers for p-type semiconductivity. This can improve the conductivity of delafossites by up to three orders of magnitude. Due to the compositorial flexibility of sol-gel processing, dopants could be introduced easily in this study by soluble precursors. However, improving the conductivity of CuAlO2 and CuAl0.5Cr0.5O2 via this method failed. Actually, this seems to be due to the fact that instead of being incorporated into the delafossite phase the dopant ions form intransparent phase impurities like spinels, which interfere with optical transmittance of the thin films. On the contrary, doping had a positive effect on the conductivity and the optical transmittance of copper chromium oxide, with magnesium being the most effective dopant. The resistivity could be decreased by more than three orders of magnitude, but in order to achieve this, much higher Mg concentrations than by other thin film deposition methods were necessary. This indicates a low doping efficiency in sol gel processed thin films, but also the ability of sol gel processing to incorporate more magnesium into the oxide than any other processing method. The extensive substitution of the chromium ions also increases the optical transmittance and allows sol gel processed thin films to draw level with thin films deposited by sputtering methods or PLD. Finally, the applicability of the delafossite thin films was proven by the asymmetric current voltage characteristics of heterojunctions between ITO and the delafossites. Shunting problems of the metallic contacts, on the other hand, reveal structural deficites of the delafossites, which should be the subject of further investigations.}, subject = {Transparent-leitendes Oxid}, language = {en} } @article{SchulzJakschSchubeletal.2014, author = {Schulz, Anita and Jaksch, Sebastian and Schubel, Rene and Wegener, Erik and Di, Zhenyu and Han, Yingchao and Meister, Annette and Kressler, J{\"o}rg and Kabanov, Alexander V. and Luxenhofer, Robert and Papadakis, Christine M. and Jordan, Rainer}, title = {Drug-Induced Morphology Switch in Drug Delivery Systems Based on Poly(2-oxazoline)s}, series = {ACS Nano}, volume = {8}, journal = {ACS Nano}, number = {3}, doi = {10.1021/nn406388t}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120766}, pages = {2686-96}, year = {2014}, abstract = {Defined aggregates of polymers such as polymeric micelles are of great importance in the development of pharmaceutical formulations. The amount of drug that can be formulated by a drug delivery system is an important issue, and most drug delivery systems suffer from their relatively low drug-loading capacity. However, as the loading capacities increase, i.e., promoted by good drug-polymer interactions, the drug may affect the morphology and stability of the micellar system. We investigated this effect in a prominent system with very high capacity for hydrophobic drugs and found extraordinary stability as well as a profound morphology change upon incorporation of paclitaxel into micelles of amphiphilic ABA poly(2-oxazoline) triblock copolymers. The hydrophilic blocks A comprised poly(2-methyl-2-oxazoline), while the middle blocks B were either just barely hydrophobic poly(2-n-butyl-2-oxazoline) or highly hydrophobic poly(2-n-nonyl-2-oxazoline). The aggregation behavior of both polymers and their formulations with varying paclitaxel contents were investigated by means of dynamic light scattering, atomic force microscopy, (cryogenic) transmission electron microscopy, and small-angle neutron scattering. While without drug, wormlike micelles were present, after incorporation of small amounts of drugs only spherical morphologies remained. Furthermore, the much more hydrophobic poly(2-n-nonyl-2-oxazoline)-containing triblock copolymer exhibited only half the capacity for paclitaxel than the poly(2-n-butyl-2-oxazoline)-containing copolymer along with a lower stability. In the latter, contents of paclitaxel of 8 wt \% or higher resulted in a raspberry-like micellar core.}, language = {en} } @phdthesis{Delporte2009, author = {Delporte, Marc}, title = {A phenomenological approach to the prediction of material behaviours during co-sintering}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-44235}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2009}, abstract = {This work deals with the sintering of multi-material composites. It aims at the establishment of an alternative to the existing complex models for sintering. The development of the associated experimental procedure is also included in this work. The developed material model must be able to predict (i) the sintering kinetics and (ii) the viscous moduli of a material. An experimental approach with free sintering and hot-forging measurements is favoured in this work. The prediction of the sintering kinetics is addressed with the construction of a map of sintering kinetics data: the Master Sintering Diagram (MSD). The MSD is based on a generalized equation for solid-state diffusion, thus is suitable for any thermal activated diffusion. The MSD allows the prediction of sintering kinetics for a large range of temperatures and external loads. A novel approach to the determination of the viscous moduli is developed in this work: the cyclic unloading method. It is a hot-forging measurement (sintering under uniaxial compression) where the applied load is released for short periods. The measurements are carried out with continuous heating, so that the viscous moduli are determined over large ranges of temperatures and densities. The advantage of this method is the measurement of the viscous moduli in anisotropic microstructures. The material model is validated in two steps. Firstly, the predictions of sintering kinetics with the MSD are compared with experimental results: changes of thermal profile and changes of load are predicted with a maximum deviation of 10\%. Secondly, the experimentally determined viscous moduli are used for the prediction of a bi-layer curvature using models for warpage from literature. The prediction is qualitatively good for a maximum deviation of 27\%. The study of a sintering glass-ceramic tape on a rigid substrate is presented. It shows that this co-sintering problem can be qualitatively investigated with requirement of the material model. The formation of anisotropy intrinsic to the hot-forging experiments is also reported in this work. It appears to be a important point to address in the future for a better understanding of the cosintering.}, subject = {Sintern}, language = {en} } @article{BorovaTokarevStahlhutetal.2020, author = {Borova, Solomiia and Tokarev, Victor and Stahlhut, Philipp and Luxenhofer, Robert}, title = {Crosslinking of hydrophilic polymers using polyperoxides}, series = {Colloid and Polymer Science}, volume = {298}, journal = {Colloid and Polymer Science}, doi = {10.1007/s00396-020-04738-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-238109}, pages = {1699-1713}, year = {2020}, abstract = {Hydrogels that can mimic mechanical properties and functions of biological tissue have attracted great interest in tissue engineering and biofabrication. In these fields, new materials and approaches to prepare hydrogels without using toxic starting materials or materials that decompose into toxic compounds remain to be sought after. Here, we report the crosslinking of commercial, unfunctionalized hydrophilic poly(2-ethyl-2-oxazoline) using peroxide copolymers in their melt. The influence of temperature, peroxide copolymer concentration, and duration of the crosslinking process has been investigated. The method allows to create hydrogels from unfunctionalized polymers in their melt and to control the mechanical properties of the resulting materials. The design of hydrogels with a suitable mechanical performance is of crucial importance in many existing and potential applications of soft materials, including medical applications.}, 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{Bockmeyer2007, author = {Bockmeyer, Matthias}, title = {Structure and Densification of Thin Films Prepared From Soluble Precursor Powders by Sol-Gel Processing}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-24577}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2007}, abstract = {The main focus of this work was to get a deeper understanding of the relationship between the structure of sol-gel films, their densification and their macroscopic cracking. First of all titania was chosen as model system. Therefore a synthesis route starting from the preparation of long-term stable amorphous redissoluble precursor powders based on acetylacetone as chelate ligand was utilized. The solubility and stability of the powders in various solvents can be determined by chemical synthesis and technological parameters. When dissolved in a solvent mixture of ethanol and 1,5-pentanediol, thin films can be easily prepared by dip-coating technique. Thereby the quality of the titania films enormously depends on the calcinations temperature and the solvent mixture is used. In order to investigate the influence of different solvents and solvent mixtures on the microstructure and densification of the precursors, the coating solutions were stripped off (sol powder) and analyzed as function of annealing temperature. It was pointed out that a high densification rate caused by the addition of 1,5-pentanediol, results in dense microstructure with trapped residual carbon. These impurities can retard the phase transformation of anatase to rutile. The analysis of so-called "film powders" scraped off multiple dip-coated substrates provides valuable information on the effect of air moisture and unidirectional densification during drying and aging on the structure of thin films. The high surface-to-volume ratio and access to air moisture determine the chemical composition of the as-prepared film, which controls shrinkage, crystallization and defect structure of the coatings. Further it was shown, that drying as a thin film results in the formation of closed pores and much denser microstructure than the respective sol powder. Without the addition of 1,5-pentanediol all -OEt moieties undergo hydrolysis reactions, which causes the formation of a rigid network. The presence of 1,5-pentanediol retards this hydrolysis reactions and provides some network plasticity. Generally the microstructure of thin films is comparatively close to the microstructure of the film powders. The addition of 1,5-pentandiol prevents hydrolysis and condensation reactions as like in the film powders. However even at 700 °C, thin films never transform to rutile, which was attributed to the tensile stresses in thin films. In thin films and in film powders as well a comparable amount of closed pores are formed during annealing. Further it was shown that most of the thin sol-gel films investigated form a dense crust on their tops during annealing. This explains why crack free films exhibit only closed pores. However, when cracks appear during thin film shrinkage in the coating, this crust is burst, which generates open porosity. The defect density in the coatings was determined by an automated analysis of surface images. The crack formation and quantity can be directly referred to tensile stresses in the coatings, which arise from hydrolysis and condensation during thin film drying and aging. Therefore when 1,5-pentanediol is added to the sol, thin film cracking was avoided, because hydrolysis and condensation reactions are retarded, which preserves a higher network flexibility. Furthermore the crack formation was significantly influenced by the atmospheric humidity that was used during the coating process, which was explained by different drying and condensation rates. Under certain chemical starting conditions water soluble precursor powders can be also obtained. In general the observations made with the water based coating solutions are mostly in agreement with the former results based on ethanol based coating solutions. For example the high surface-to-volume ratio of film powders compared to sol powders also significantly enhances film drying and densification. The addition of 1,5-pentanediol also clearly contributes to their densification behavior and phase evolution. As seen before in the case of ethanol based coatings, 1,5-pentanediol enhances the stability towards hydrolysis and condensation reactions and preserves some network plasticity. Therefore coatings prepared without the addition of 1,5-pentanediol already form cracks during film drying and aging because of tensile stresses. Thus, the addition of 1,5-pentanediol results in a reduction/prevention of crack formation. Nevertheless some differences were observed, i.e. the critical single coating film thickness of ethanol based coatings is nearly twice that of water based coatings. This was explained by the different surface tensions of the basis solvents, which during thin film drying causes significantly higher capillary forces and tensile stresses in water based coatings. When acetylacetone is replaced by triethanolamine as chelating ligand for titanium also re-dissolvable precursor powders can be synthesized. The film powders combine a high hydrolytic stability of the precursor with sufficient intermediate network flexibility. The different type of organics changes the drying and densification behavior: i.e. in contrast to film powders obtained from acetylacetone based precursor powders the structure of triethanolamine based film powders is unaffected by the thin film drying process. This high hydrolytic stability and plasticity of this precursor allows the preparation of defect free coatings up to single film thickness of 300 nm. However triethanolamine based thin films present at intermediary annealing temperatures a distinctively different microstructure compared to acetylacetone based films. The general validity of the conclusions was proved on the basis of zirconia coatings that were also prepared by the use of re-dissolvable precursor powders. In principle all conclusions concerning the interconnection of precursor chemistry, film formation, densification and structure were transferable to the respective zirconia coatings. Differences mainly arise only from differential material properties i.e. bulk density. Finally, it has been pointed out that the findings obtained on the densification behavior of thinsol-gel films are also a valuable tool for improved explanations of other important scientific questions concerning sol-gel films, i.e. scratch resistance of sol-gel coatings, fiber -bridging and - degradation of sol-gel coated fibers.}, subject = {Sol-Gel-Verfahren}, language = {en} } @article{LuxenhoferFetsch2013, author = {Luxenhofer, Robert and Fetsch, Corinna}, title = {Thermal Properties of Aliphatic Polypeptoids}, series = {Polymers}, journal = {Polymers}, doi = {10.3390/polym5010112}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96333}, year = {2013}, abstract = {A series of polypeptoid homopolymers bearing short (C1-C5) side chains of degrees of polymerization of 10-100 are studied with respect to thermal stability, glass transition and melting points. Thermogravimetric analysis of polypeptoids suggests stability to >200 °C. The study of the glass transition temperatures by differential scanning calorimetry revealed two dependencies. On the one hand an extension of the side chain by constant degree of polymerization decrease the glass transition temperatures (Tg) and on the other hand a raise of the degree of polymerization by constant side chain length leads to an increase of the Tg to a constant value. Melting points were observed for polypeptoids with a side chain comprising not less than three methyl carbon atoms. X-ray diffraction of polysarcosine and poly(N-ethylglycine) corroborates the observed lack of melting points and thus, their amorphous nature. Diffractograms of the other investigated polypeptoids imply that crystalline domains exist in the polymer powder.}, language = {en} } @phdthesis{Hu2022, author = {Hu, Chen}, title = {Novel hybrid hydrogels based on poly(2-oxazoline)}, doi = {10.25972/OPUS-27935}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-279354}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Motivated by the great potential offered by the combination of additive manufacturing technology and hydrogels, especially in the field of tissue engineering and regenerative medicine, a series of novel hybrid hydrogel inks were developed based on the recently described thermogelling poly(2-oxazoline)s-block-poly(2-oxazine)s diblock copolymers, which may help to expand the platform of available hydrogel inks for this transformative 3D printing technology (Fig. 5.1). In the present thesis, the first reported thermogelling polymer solely consisting of POx and POzi, i.e., the diblock copolymer PMeOx-b-PnPrOzi comprising a hydrophilic block (PMeOx) and a thermoresponsive block (PnPrOzi), was selected and used as a proof-of-concept for the preparation of three novel hybrid hydrogels. Therefore, three batches of the diblock copolymers with a DP of 100 were synthesized for the study of three different hybrid hydrogels with a special focus on their suitability as (bio)inks for extrusion-based 3D printing. The PMeOx-b-PnPrOzi diblock copolymer solution shows a temperature induced reversible gelation behavior above a critical polymer concentration of 20 wt\%, as described for the Pluronic F127 solution but with a unique gelation mechanism, working through the formation of a bicontinuous sponge-like structure from the physically crosslinked vesicles. Specially, its intrinsic shear thinning behavior and excellent recovery property with a certain yield point make it a promising ink candidate for extrusion-based printing technology. Increasing the polymer concentration is the most traditional approach to improve the printability of an ink material, and serve as the major strategy available to improve the printability of PMeOx-b-PnPrOzi systems prior to this work. From the analysis of rheological properties related to printability, it came a conclusion that increasing the copolymer concentration does improve the hydrogel strength and thus the printability. However, such improvement is very limited and usually leads to other problems such as more viscous systems and stringent requirements on the printers, which are not ideal for the printing process and applications especially in the cell-embedded biofabrication field. POx-b-POzi/clay Hybrid Hydrogel An alternative method proposed to improve the printability of this thermoresponsive hydrogel ink is through nanoclay (Laponite XLG) addition, i.e., the first hybrid hydrogel system of PMeOx-b-PnPrOzi/clay (also named shortly as POx-b-POzi/clay) in this thesis. To optimize the viscoelastic properties of the ink material, Laponite XLG acted as a reinforcement additive and a physically crosslinker was blended with the copolymers. Compared with the pristine copolymer solution of PMeOx-b-PnPrOzi, the hybrid PMeOx-b-PnPrOzi/clay solution well retained the temperature induced gelation performance of the copolymers. The obtained hybrid hydrogels exhibited a rapid in situ reversible thermogelation at a physiological relevant Tgel of around 15 ℃ and a rapid recovery of viscoelastic properties within a few seconds. More importantly, with the addition of only a small amount of 1.2 wt\% clay, it exhibited obviously enhanced shear thinning character (n = 0.02), yield stress (240 Pa) and mechanical strength (storage modulus over 5 kPa). With this novel hybrid hydrogel, real three-dimensional constructs with multiple layers and various geometries are generation with greatly enhanced shape fidelity and resolution. In this context, the thermogelling properties of the hybrid hydrogels over a copolymer concentration range of 10-20 wt\% and a clay concentration of 0-4 wt\% were systematically investigated, and from which a printable window was obtained from the laboratory as a reference. In fact, the printing performance of an ink is not only determined by the intrinsic physicochemical properties of the material, but is also influenced by the external printing environments as well as the printer parameter settings. All the printing experiments in this study were conducted under a relatively optimized conditions obtained from preliminary experiments. In future work, the relationship between material rheology properties, printer parameters and printing performance could be systematically explored. Such a fundamental study will help to develop models that allows the prediction and comparison of printing results from different researches based on the parameters available through rheology, which is very beneficial for further development of more advanced ink systems. Although the printability has been significantly improved by the addition of nanoclay Laponite XLG, the hybrid hydrogels and their printed constructs still suffer from some major limitations. For example, these materials are still thermoresponsive, which will cause the printed constructs to collapse when the environment temperature changes below their Tgel. In addition, the formed hydrogel constructs are mechanical too weak for load-bearing applications, and the allowed incubation time is very limited during media exchange/addition as it will lead to dissolution of the hydrogels due to dilution effects. Therefore, it is essential to establish a second (chemical or physical) crosslinking mechanism that allows further solidification of the gels after printing. It should be kept in mind that the second crosslinking step will eliminate the thermoresponsive behavior of the gels and thus the possibility of cell recovery. In this case, besides through the traditional approach of copolymer modification to realize further crosslinking, like one of the well-known post-polymerization modification approach Diels-Alder reaction,[430] designing of interpenetrating networks (IPN) hydrogels serves as one of the major strategy for advanced (bio)ink preparation.[311] Therefore, the second hybrid hydrogel system of PMeOx-b-PnPrOzi/PDMAA/clay (also named shortly as POx-b-POzi/PDMAA/clay) was developed in this thesis, which is a 3D printable and highly stretchable ternary organic-inorganic IPN hydrogel. POx-b-POzi/PDMAA/clay Hybrid Hydrogel The nanocomposite IPN hydrogel combines a thermoresponsive hydrogel with clay described above and in situ polymerized poly(N, N-dimethylacrylamide). Before in situ polymerization, the thermoresponsive hydrogel precursors exhibited thermogelling behavior (Tgel ~ 25 ℃, G' ~ 6 kPa) and shear thinning properties, making the system well-suited for extrusion-based 3D printing. After chemical curing of the 3D-printed constructs by free radical polymerization, the resulting IPN hydrogels show excellent mechanical strength with a high stretchability to a tensile strain at break exceeding 550\%. The hybrid hydrogel can sustain a high stretching deformation and recover quickly due to the energy dissipation from the non-covalent interactions. With this hybrid hydrogel, integrating with the advanced 3D-printing technique, various 3D constructs can be printed and cured successfully with high shape fidelity and geometric accuracy. In this context, we also investigated the possibility of acrylic acid (AA) and 2-hydroxyethylmethacrylate (HEMA) as alternative hydrogel precursors. However, the addition of these two monomers affected the thermogelation of POx-b-POzi in an unfavorable manner, as these monomers competed more effectively with water molecules, preventing the hydration of nPrOzi block at lower temperatures and therefore, the liquefaction of the gels. Furthermore, the influence of the printing process and direction on the mechanical properties of the hydrogel was investigated and compared with the corresponding bulk materials obtained from a mold. No significant effects from the additive manufacturing process were observed due to a homogeneously adhesion and merging between sequentially deposited layers. In the future, further studies on the specific performance differences among hydrogels fabricated at different printing directions/speeds would be of great interest to the community, as this allows for a more accurately control and better predict of the printed structures. This newly developed hybrid IPN hydrogel is expected to expand the material toolbox available for hydrogel-based 3D printing, and may be interesting for a wide range of applications including tissue engineering, drug delivery, soft robotics, and additive manufacturing in general. However, in this case, the low toxicity from the monomer DMAA and other small molecules residuals in the polymerized hydrogels made this hybrid hydrogel not ideal for bioprinting in the field of biofabrication. For this problem, cyto-/biocompatible monomers such as polyethylene glycol diacrylate (PEGDA) can be used as an alternative, while the overall properties of the hydrogels including mechanical properties should be re-evaluated accordingly. Moreover, the swelling behavior of the hydrogels should also be taken into account, as it may most likely affect the mechanical strength and geometry size of the printed scaffold, but is often be overlooked after printing. For example, regarding the specific hybrid hydrogel POx-b-POzi/PDMAA/clay in this work, an equilibrium swelling ratio of 1100\% was determined. The printed hydrogel cuboid experienced a volume increasing over 6-fold after equilibrium swelling in water, and became mechanical fragile due to the formation of a swollen hydrogel network absorbing large amount of water. POx-b-POzi/Alg/clay Hybrid Hydrogel In the final part of this dissertation, to enable the cell-loaded bioprinting and long-term cell culture, the third hybrid hydrogel system POx-b-POzi/Alg/clay was introduced by replacing the monomer DMAA to the natural polysaccharides alginate. Initially, detailed rheological characterization and mechanical tests were performed to evaluate their printability and mechanically properties. Subsequently, some simple patterns were printed with the optimized hydrogel precursor solutions for the preliminary filament fusion and collapse test before proceeding to more complex printings. The fibers showed a sufficient stability which allows the creation of large structures with a height of a few centimeters and a suspended filament up to centimeter. Accordingly, various 3D constructs including suspended filaments were printed successfully with high stackability and shape fidelity. The structure after extrusion was physical crosslinked easily by soaking in CaCl2 solution and, thereafter exhibited a good mechanical flexibility and long-term stability. Interestingly, the mechanical strength and geometry size of the generated scaffolds were well maintained over a culture period of weeks in water, which is of great importance for clinical applications. In addition, the post-printing ionic crosslinking of alginate could also be realized by other di/trivalent cations such as Fe3+ and Tb3+. Subsequently, the cell-laden printing with this hybrid hydrogel and post-printing crosslinking by Ca2+ ions highlighting its feasibility for 3D bioprinting. WST-1 assay of fibroblast suggested no-dose dependent cytocompatibility of the hydrogel precursor solution. The cell distribution was uniform throughout the printed construct, and proliferated with high cell viability during the 21 days culture. The presented hybrid approach, utilizing the beneficial properties of the POx-b-POzi base material, could be interesting for a wide range of bioprinting applications and potentially enabling also other biological bioinks such as collagen, hyaluronic acid, decellularized extracellular matrix or cellulose based bioinks. Although the results look promising and the developed hydrogel is an important bioink candidate, the long-term in vitro cell studies with different cell lines and clinical model establishment are still under investigation, which remains a long road but is of great importance before realizing real clinical application. Last but not least, the improvement to the printability of thermogelling POx/POzi-based copolymers by the clay Laponite XLG was also demonstrated in another thermogelling copolymer PEtOx-b-PnPrOzi. This suggests that the addition of clay may be a general strategy to improve the printability of such polymers. Despite these advances in this work which significantly extended the (bio)material platform of additive manufacturing technology, the competition is still fierce and more work should be done in the further to reveal the potential and limitations of this kind of new and promising candidate (bio)ink materials. It is also highly expected for further creative works based on the thermogelling POx/POzi polymers, such as crosslinking in Ca2+ solution containing monomer acrylamide to prepare printable and mechanically tough hydrogels, research on POx-based support bath material, and print of clinically more relevant sophisticated structures such as 3D microvascular networks omnidirectionally.}, subject = {Funktionsgel}, 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} } @article{HahnBeudertGutmannetal.2021, author = {Hahn, Lukas and Beudert, Matthias and Gutmann, Marcus and Keßler, Larissa and Stahlhut, Philipp and Fischer, Lena and Karakaya, Emine and Lorson, Thomas and Thievessen, Ingo and Detsch, Rainer and L{\"u}hmann, Tessa and Luxenhofer, Robert}, title = {From Thermogelling Hydrogels toward Functional Bioinks: Controlled Modification and Cytocompatible Crosslinking}, series = {Macromolecular Bioscience}, volume = {21}, journal = {Macromolecular Bioscience}, number = {10}, doi = {10.1002/mabi.202100122}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257542}, year = {2021}, abstract = {Hydrogels are key components in bioink formulations to ensure printability and stability in biofabrication. In this study, a well-known Diels-Alder two-step post-polymerization modification approach is introduced into thermogelling diblock copolymers, comprising poly(2-methyl-2-oxazoline) and thermoresponsive poly(2-n-propyl-2-oxazine). The diblock copolymers are partially hydrolyzed and subsequently modified by acid/amine coupling with furan and maleimide moieties. While the thermogelling and shear-thinning properties allow excellent printability, trigger-less cell-friendly Diels-Alder click-chemistry yields long-term shape-fidelity. The introduced platform enables easy incorporation of cell-binding moieties (RGD-peptide) for cellular interaction. The hydrogel is functionalized with RGD-peptides using thiol-maleimide chemistry and cell proliferation as well as morphology of fibroblasts seeded on top of the hydrogels confirm the cell adhesion facilitated by the peptides. Finally, bioink formulations are tested for biocompatibility by incorporating fibroblasts homogenously inside the polymer solution pre-printing. After the printing and crosslinking process good cytocompatibility is confirmed. The established bioink system combines a two-step approach by physical precursor gelation followed by an additional chemical stabilization, offering a broad versatility for further biomechanical adaptation or bioresponsive peptide modification.}, language = {en} } @article{StrasserSchrauthDembskietal.2017, author = {Straßer, Marion and Schrauth, Joachim H. X. and Dembski, Sofia and Haddad, Daniel and Ahrens, Bernd and Schweizer, Stefan and Christ, Bastian and Cubukova, Alevtina and Metzger, Marco and Walles, Heike and Jakob, Peter M. and Sextl, Gerhard}, title = {Calcium fluoride based multifunctional nanoparticles for multimodal imaging}, series = {Beilstein Journal of Nanotechnology}, volume = {8}, journal = {Beilstein Journal of Nanotechnology}, doi = {10.3762/bjnano.8.148}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170657}, pages = {1484-1493}, year = {2017}, abstract = {New multifunctional nanoparticles (NPs) that can be used as contrast agents (CA) in different imaging techniques, such as photoluminescence (PL) microscopy and magnetic resonance imaging (MRI), open new possibilities for medical imaging, e.g., in the fields of diagnostics or tissue characterization in regenerative medicine. The focus of this study is on the synthesis and characterization of CaF\(_{2}\):(Tb\(^{3+}\),Gd\(^{3+}\)) NPs. Fabricated in a wet-chemical procedure, the spherical NPs with a diameter of 5-10 nm show a crystalline structure. Simultaneous doping of the NPs with different lanthanide ions, leading to paramagnetism and fluorescence, makes them suitable for MR and PL imaging. Owing to the Gd\(^{3+}\) ions on the surface, the NPs reduce the MR T\(_{1}\) relaxation time constant as a function of their concentration. Thus, the NPs can be used as a MRI CA with a mean relaxivity of about r = 0.471 mL·mg\(^{-1}\)·s\(^{-1}\). Repeated MRI examinations of four different batches prove the reproducibility of the NP synthesis and determine the long-term stability of the CAs. No cytotoxicity of NP concentrations between 0.5 and 1 mg·mL\(^{-1}\) was observed after exposure to human dermal fibroblasts over 24 h. Overall this study shows, that the CaF\(_{2}\):(Tb\(^{3+}\),Gd\(^{3+}\)) NPs are suitable for medical imaging.}, language = {en} } @article{BelkaNickelKurth2019, author = {Belka, Janina and Nickel, Joachim and Kurth, Dirk G.}, title = {Growth on metallo-supramolecular coordination polyelectrolyte (MEPE) stimulates osteogenic differentiation of human osteosarcoma cells (MG63) and human bone marrow derived mesenchymal stem cells}, series = {Polymers}, volume = {11}, journal = {Polymers}, number = {7}, issn = {2073-4360}, doi = {10.3390/polym11071090}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197264}, pages = {1090}, year = {2019}, abstract = {Background: Culturing of cells is typically performed on standard tissue culture plates generating growth conditions, which in general do not reflect the native three-dimensional cellular environment. Recent investigations provide insights in parameters, which strongly affect the general cellular behavior triggering essential processes such as cell differentiation. The physical properties of the used material, such as stiffness, roughness, or topology, as well as the chemical composition of the cell-surface interface are shown to play a key role in the initiation of particular cellular responses. Methods: We extended our previous research, which identified thin films of metallo-supramolecular coordination polyelectrolytes (MEPEs) as substrate to trigger the differentiation of muscular precursor cells. Results: Here, we show that the same MEPEs similarly stimulate the osteogenic differentiation of pre-osteoblasts. Remarkably, MEPE modified surfaces also trigger the differentiation of primary bone derived mesenchymal stem cells (BMSCs) towards the osteogenic lineage. Conclusion: This result leads to the conclusion that these surfaces individually support the specification of cell differentiation toward lineages that correspond to the natural commitment of the particular cell types. We, therefore, propose that Fe-MEPEs may be used as scaffold for the treatment of defects at least in muscular or bone tissue.}, language = {en} } @article{PetschkeHelmStaab2019, author = {Petschke, Danny and Helm, Ricardo and Staab, Torsten E.M.}, title = {Data on pure tin by Positron Annihilation Lifetime Spectroscopy (PALS) acquired with a semi-analog/digital setup using DDRS4PALS}, series = {Data in Brief}, volume = {22}, journal = {Data in Brief}, doi = {10.1016/j.dib.2018.11.121}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177698}, pages = {16-29}, year = {2019}, abstract = {Positron annihilation lifetime spectroscopy (PALS) provides a powerful technique for non-destructive microstructure investigations in a broad field of material classes such as metals, semiconductors, polymers or porous glasses. Even though this method is well established for more than five decades, no proper standardization for the used setup configuration and subsequent data processing exists. Eventually, this could lead to an insufficiency of data reproducibility and avoidable deviations. Here we present experimentally obtained and simulated data of positron lifetime spectra at various statistics measured on pure tin (4N-Sn) by using a semi-analog/digital setup, where the digital section consists of the DRS4 evaluation board, "Design and performance of the 6 GHz waveform digitizing chip DRS4" [1]. The analog section consists of nuclear instrument modules (NIM), which externally trigger the DRS4 evaluation board to reduce the digitization and, thus, increase the acquisition efficiency. For the experimentally obtained lifetime spectra, 22Na sealed in Kapton foil served as a positron source, whereas 60Co was used for the acquisition of the prompt spectrum, i.e. the quasi instrument response function. Both types of measurements were carried out under the same conditions. All necessary data and information regarding the data acquisition and data reduction are provided to allow reproducibility by other research groups.}, language = {en} } @article{HahnLuxenhoferHeltenetal.2021, author = {Hahn, Lukas and Luxenhofer, Robert and Helten, Holger and Forster, Stefan and Fritze, Lars and Polzin, Lando and Keßler, Larissa}, title = {ABA Type Amphiphiles with Poly(2-benzhydryl-2-oxazine) Moieties: Synthesis, Characterization and Inverse Thermogelation}, series = {Macromolecular Chemistry and Physics}, volume = {222}, journal = {Macromolecular Chemistry and Physics}, number = {17}, doi = {10.1002/macp.202100114}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265124}, year = {2021}, abstract = {Thermoresponsive polymers are frequently involved in the development of materials for various applications. Here, polymers containing poly(2- benzhydryl-2-oxazine) (pBhOzi) repeating units are described for the first time. The homopolymer pBhOzi and an ABA type amphiphile comprising two flanking hydrophilic A blocks of poly(2-methyl-2-oxazoline) (pMeOx) and the hydrophobic aromatic pBhOzi central B block (pMeOx-b-pBhOzi-b-pMeOx) are synthesized and the latter is shown to exhibit inverse thermogelling properties at concentrations of 20 wt.\% in water. This behavior stands in contrast to a homologue ABA amphiphile consisting of a central poly(2-benzhydryl-2-oxazoline) block (pMeOx-b-pBhOx-b-pMeOx). No inverse thermogelling is observed with this polymer even at 25 wt.\%. For 25 wt.\% pMeOx-b-pBhOzi-b-pMeOx, a surprisingly high storage modulus of ≈22 kPa and high values for the yield and flow points of 480 Pa and 1.3 kPa are obtained. Exceeding the yield point, pronounced shear thinning is observed. Interestingly, only little difference between self-assemblies of pMeOx-b-pBhOzi-b-pMeOx and pMeOx-b-pBhOx-b-pMeOx is observed by dynamic light scattering while transmission electron microscopy images suggest that the micelles of pMeOx-b-pBhOzi-b-pMeOx interact through their hydrophilic coronas, which is probably decisive for the gel formation. Overall, this study introduces new building blocks for poly(2-oxazoline) and poly(2-oxazine)-based self-assemblies, but additional studies will be needed to unravel the exact mechanism.}, language = {en} } @article{LuebtowMarciniakSchmiedeletal.2019, author = {L{\"u}btow, Michael M. and Marciniak, Henning and Schmiedel, Alexander and Roos, Markus and Lambert, Christoph and Luxenhofer, Robert}, title = {Ultra-high to ultra-low drug loaded micelles: Probing host-guest interactions by fluorescence spectroscopy}, series = {Chemistry - A European Journal}, volume = {25}, journal = {Chemistry - A European Journal}, number = {54}, doi = {10.1002/chem.201902619}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206128}, pages = {12601-12610}, year = {2019}, abstract = {Polymer micelles are an attractive means to solubilize water insoluble compounds such as drugs. Drug loading, formulations stability and control over drug release are crucial factors for drug-loaded polymer micelles. The interactions between the polymeric host and the guest molecules are considered critical to control these factors but typically barely understood. Here, we compare two isomeric polymer micelles, one of which enables ultra-high curcumin loading exceeding 50 wt.\%, while the other allows a drug loading of only 25 wt.\%. In the low capacity micelles, steady-state fluorescence revealed a very unusual feature of curcumin fluorescence, a high energy emission at 510 nm. Time-resolved fluorescence upconversion showed that the fluorescence life time of the corresponding species is too short in the high-capacity micelles, preventing an observable emission in steady-state. Therefore, contrary to common perception, stronger interactions between host and guest can be detrimental to the drug loading in polymer micelles.}, subject = {Polymer-drug interaction}, language = {en} } @article{ZahoranovaLuxenhofer2021, author = {Zahoranov{\´a}, Anna and Luxenhofer, Robert}, title = {Poly(2-oxazoline)- and Poly(2-oxazine)-Based Self-Assemblies, Polyplexes, and Drug Nanoformulations—An Update}, series = {Advanced Healthcare Materials}, volume = {10}, journal = {Advanced Healthcare Materials}, number = {6}, doi = {10.1002/adhm.202001382}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225833}, year = {2021}, abstract = {For many decades, poly(2-oxazoline)s and poly(2-oxazine)s, two closely related families of polymers, have led the life of a rather obscure research topic with only a few research groups world-wide working with them. This has changed in the last five to ten years, presumably triggered significantly by very promising clinical trials of the first poly(2-oxazoline)-based drug conjugate. The huge chemical and structural toolbox poly(2-oxazoline)s and poly(2-oxazine)s has been extended very significantly in the last few years, but their potential still remains largely untapped. Here, specifically, the developments in macromolecular self-assemblies and non-covalent drug delivery systems such as polyplexes and drug nanoformulations based on poly(2-oxazoline)s and poly(2-oxazine)s are reviewed. This highly dynamic field benefits particularly from the extensive synthetic toolbox poly(2-oxazoline)s and poly(2-oxazine)s offer and also may have the largest potential for a further development. It is expected that the research dynamics will remain high in the next few years, particularly as more about the safety and therapeutic potential of poly(2-oxazoline)s and poly(2-oxazine)s is learned.}, language = {en} }