@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{Luebtow2020,
  author    = {L{\"u}btow, Michael M.},
  title     = {Structure-property relationships in poly(2-oxazoline)/poly(2-oxazine) based drug formulations},
  doi       = {10.25972/OPUS-19338},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193387},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {According to estimates, more than 40\% of all new chemical entities developed in pharmaceutical industry are practically insoluble in water. Naturally, the demand for excipients which increase the water solubility and thus, the bioavailability of such hydrophobic drugs is enormous. Poly(2-oxazoline)s (POx) are currently intensively discussed as highly versatile class of biomaterials. Although selected POx based micellar drug formulations exhibit extraordinarily high drug loadings > 50 wt.\% enabling high anti-tumor efficacies in vivo, the formulation of other hydrophobic compounds has failed. This casts doubt on the general understanding in which a hydrophobic active pharmaceutical ingredient is dissolved rather unspecifically in the hydrophobic core of the micelles following the fundamental concept of "like dissolves like". Therefore, a closer look at the interactions between all components within a formulation becomes increasingly important. To do so, a large vehicle platform was synthesized, loaded with various hydrophobic drugs of different structure, and the formulations subsequently characterized with conventional and less conventional techniques. The obtained in-depth insights helped to develop a more thorough understanding about the interaction of polymer and incorporated API finally revealing morphologies deviating from a classical core/shell structure. During these studies, the scarcely investigated polymer class of poly(2-oxazine)s (POzi) was found as promising drug-delivery vehicle for hydrophobic drugs. Apart from this fundamental research, the anti-tumor efficacy of the two APIs curcumin and atorvastatin has been studied in more detail. To increase the scope of POx and POzi based formulations designed for intravenous administration, a curcumin loaded hydrogel was developed as injectable drug-depot.},
  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{Fetsch2014,
  author    = {Fetsch, Corinna},
  title     = {Polypeptoide - Synthese und Charakterisierung},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-109157},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Die vorliegende Arbeit befasste sich mit der bisher relativ unbekannten Polymerklasse der Polypeptoide, die hinsichtlich ihrer Verwendung als Biomaterial n{\"a}her untersucht werden sollte. Hierbei war die Untersuchung des Polymerisationssystems ein wesentlicher Schwerpunkt. Dies beinhaltete zum einen die Synthesen verschiedener Monomere sowie deren Polymerisationskinetiken und zum anderen Studien {\"u}ber die Stabilit{\"a}t des aktiven Kettenendes. Um mehr {\"u}ber die Polypeptoide zu erfahren, wurden die erhaltenen Homopolymere nach der Strukturanalyse hinsichtlich ihrer physikochemischen Eigen-schaften untersucht. Im Anschluss erfolgte die Synthese von (amphiphilen) Blockco-polypeptoiden, die sich in w{\"a}ssrigen L{\"o}sungen zu definierten Morphologien zusammen-lagern. Die resultierenden Morphologien, sowohl mizellare als auch vesikul{\"a}re Strukturen, wurden mit verschiedenen Methoden, wie z. B. der Pyren-Fluoreszenz-Spektroskpie und der dynamischen Lichtstreuung, untersucht. Erste Erkenntnisse {\"u}ber die Biokompatibilit{\"a}t der Polypeptoide sollte die Bestimmung der Zellviabilit{\"a}t in verschiedenen Polymerl{\"o}sungen liefern. Die verschiedenen Studien {\"u}ber die Polypeptoide zeigten, dass diese Polymerklasse {\"u}ber eine besonders lebende Polymerisation synthetisiert werden kann. Dabei resultieren Produkte, die sich durch eine Poisson-Verteilung und eine hohe Endgruppengenauigkeit auszeichnen. Zus{\"a}tzlich bestehen Polypeptoide aus einem abbaubaren R{\"u}ckgrat und, im Vergleich zu den Polypeptiden, besitzen sie eine erh{\"o}hte proteolytische Stabilit{\"a}t. Amphiphile Blockcopolypeptoide sind zudem in der Lage, sich in L{\"o}sung zu verschiedenen Morphologien anzuordnen. Durch die Variierung der Seitenkette und des f kann sowohl die Selbstorganisation als auch das Mikroumfeld der Aggregate abgestimmt werden. Dar{\"u}ber hinaus k{\"o}nnen die amphiphile Blockcopolymere, die sich zu Mizellen anordnen, hydrophobe Substanzen solubilisieren. Polypeptoide liefern all die n{\"o}tige chemische Vielseitigkeit und potentielle Biokompatibilit{\"a}t, um bestehende sowie neuartige Probleme in biomedizinischen Anwendungen zu bew{\"a}ltigen. Zuk{\"u}nftige in vivo und in vitro Test werden das Potential, aber auch die Grenzen dieser neuen Polymerklasse als Biomaterial zeigen.},
  subject      = {Polymerisation},
  language  = {de}
}