Institut für Funktionsmaterialien und Biofabrikation
Refine
Has Fulltext
- yes (13)
Is part of the Bibliography
- yes (13)
Year of publication
- 2021 (13) (remove)
Document Type
- Journal article (9)
- Doctoral Thesis (4)
Keywords
- biofabrication (2)
- 3D-Druck (1)
- Artificial photosynthesis (1)
- Bassanit (1)
- Biomaterial (1)
- Electrochemistry (1)
- Elektrokinetik (1)
- Elektrophorese (1)
- Elektrostatisches Feld (1)
- Fotokatalyse (1)
Institute
Sonstige beteiligte Institutionen
Additive manufacturing or 3D printing as an umbrella term for various materials processing methods has distinct advantages over many other processing methods, including the ability to generate highly complex shapes and designs. However, the performance of any produced part not only depends on the material used and its shape, but is also critically dependent on its surface properties. Important features, such as wetting or fouling, critically depend mainly on the immediate surface energy. To gain control over the surface chemistry post-processing modifications are generally necessary, since it′s not a feature of additive manufacturing. Here, we report on the use of initiator and catalyst-free photografting and photopolymerization for the hydrophilic modification of microfiber scaffolds obtained from hydrophobic medical-grade poly(ε-caprolactone) via melt-electrowriting. Contact angle measurements and Raman spectroscopy confirms the formation of a more hydrophilic coating of poly(2-hydroxyethyl methacrylate). Apart from surface modification, we also observe bulk polymerization, which is expected for this method, and currently limits the controllability of this procedure.
As one kind of “smart” material, thermogelling polymers find applications in biofabrication, drug delivery and regenerative medicine. In this work, we report a thermosensitive poly(2-oxazoline)/poly(2-oxazine) based diblock copolymer comprising thermosensitive/moderately hydrophobic poly(2-N-propyl-2-oxazine) (pPrOzi) and thermosensitive/moderately hydrophilic poly(2-ethyl-2-oxazoline) (pEtOx). Hydrogels were only formed when block length exceeded certain length (≈100 repeat units). The tube inversion and rheological tests showed that the material has then a reversible sol-gel transition above 25 wt.% concentration. Rheological tests further revealed a gel strength around 3 kPa, high shear thinning property and rapid shear recovery after stress, which are highly desirable properties for extrusion based three-dimensional (3D) (bio) printing. Attributed to the rheology profile, well resolved printability and high stackability (with added laponite) was also possible. (Cryo) scanning electron microscopy exhibited a highly porous, interconnected, 3D network. The sol-state at lower temperatures (in ice bath) facilitated the homogeneous distribution of (fluorescently labelled) human adipose derived stem cells (hADSCs) in the hydrogel matrix. Post-printing live/dead assays revealed that the hADSCs encapsulated within the hydrogel remained viable (≈97%). This thermoreversible and (bio) printable hydrogel demonstrated promising properties for use in tissue engineering applications.
Adrenocortical carcinoma (ACC) is a malignant tumor originating from the adrenal gland cortex with a heterogeneous but overall dismal prognosis in advanced stages. For more than 50 years, mitotane has remained a cornerstone for the treatment of ACC as adjuvant and palliative therapy. It has a very poor aqueous solubility of 0.1 mg/l and high partition coefficient in octanol/water (log P) value of 6. The commercially available dosage form is 500 mg tablets (Lysodren®). Even at doses up to 6 g/day (12 tablets in divided doses) for several months, > 50% patients do not achieve therapeutic plasma concentration > 14 mg/l due to poor water solubility, large volume of distribution and inter/intra-individual variability in bioavailability. This article aims to give a concise update of the clinical challenges associated with the administration of high-dose mitotane oral therapy which encompass the issues of poor bioavailability, difficult-to-predict pharmacokinetics and associated adverse events. Moreover, we present recent efforts to improve mitotane formulations. Their success has been limited, and we therefore propose an injectable mitotane formulation instead of oral administration, which could bypass many of the main issues associated with high-dose oral mitotane therapy. A parenteral administration of mitotane could not only help to alleviate the adverse effects but also circumvent the variable oral absorption, give better control over therapeutic plasma mitotane concentration and potentially shorten the time to achieve therapeutic drug plasma concentrations considerably.
Mitotane as tablet form is currently the standard treatment for adrenocortical carcinoma. It has been used for 5 decades but suffers from highly variable responses in patients, subsequent adverse effects and overall lower response rate. This can be fundamentally linked to the exceedingly poor water solubility of mitotane itself. In terms of enhancing water solubility, a few research groups have attempted to develop better formulations of mitotane to overcome the issues associated with tablet dosage form. However, the success rate was limited, and these formulations did not make it into the clinics. In this article, we have comprehensively reviewed the properties of these formulations and discuss the reasons for their limited utility. Furthermore, we discuss a recently developed mitotane nanoformulation that led us to propose a novel approach to mitotane therapy, where intravenous delivery supplements the standard oral administration. With this article, we combine the current state of knowledge as a single piece of information about the various problems associated with the use of mitotane tablets, and herein we postulate the development of a new injectable mitotane formulation, which can potentially circumvent the major problems associated to mitotane's poor water solubility.
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.
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.
Oxidative precipitation is a facile synthesis method to obtain ferromagnetic iron oxide nanoparticles from ferrous salts—with unexplored potential. The concentration of base and oxidant alone strongly affects the particle's structure and thus their magnetic properties despite the same material, magnetite (Fe\(_{3}\)O\(_{4}\)), is obtained when precipitated with potassium hydroxide (KOH) from ferrous sulfate (FeSO\(_{4}\)) and treated with potassium nitrate (KNO\(_{3}\)) at appropriate temperature. Depending on the potassium hydroxide and potassium nitrate concentrations, it is possible to obtain a series of different types of either single crystals or mesocrystals. The time‐dependent mesocrystal evolution can be revealed via electron microscopy and provides insights into the process of oriented attachment, yielding faceted particles, showing a facet‐dependent reactivity. It is found that it is the nitrate and hydroxide concentration that influences the ligand exchange process and thus the crystallization pathways. The presence of sulfate ions contributes to the mesocrystal evolution as well, as sulfate apparently hinders further crystal fusion, as revealed via infrared spectroscopy. Finally, it is found that nitrite, as one possible and ecologically highly relevant reduction product occurring in nature in context with iron, only evolves if the reaction is quantitative.
In this study, we investigate the impact of N-methylation on the electronic and photophysical properties of both homoleptic and heteroleptic Ru(II) bis-terpyridine complexes based on the recently reported ligand 4’-(4-bromophenyl)-4,4’’’: 4’’,4’’’’-dipyr-idinyl-2,2’ : 6’,2’’-terpyridine (Bipytpy), with pyridine substituents in the 4- and 4’’-position. The first reduction of the methylated complexes takes place at the pyridinium site and is observed as multi-electron process. Following N-methylation, the complexes exhibit higher luminescence quantum yields and longer excited-state lifetimes. Interestingly, the photophysical properties of the heteroleptic and homoleptic complexes are rather similar. TD-DFT calculations support the experimental results. Furthermore, the complexes are tested as photosensitizers for photocatalytic hydrogen production, as the parent complex 1[Ru(Bipytpy)(Tolyltpy)](PF \(_6\))\(_2\) (Tolyltpy: 4’-tolyl-2,2’: 6’,2’’-terpyri-dine) was recently shown to be active and highly stable underphotocatalytic conditions. However, the methylated complexes reported herein are inactive as photosensitizers under the chosen conditions, presumably due to loss of the methyl groups, converting them to the non-methylated parent complexes.
This thesis investigates different ligand designs for Ru(II) complexes and the activity of the complexes as photosensitizer (PS) in photocatalytic hydrogen evolution. The catalytic system typically contains a catalyst, a sacrificial electron donor (SED) and a PS, which needs to exhibit strong absorption and luminescence, as well as reversible redox behavior. Electron-withdrawing pyridine substituents on the terpyridine metal ion receptor result in an increase of excited-state lifetime and quantum yield (Φ = 74*10-5; τ = 3.8 ns) and lead to complex III-C1 exhibiting activity as PS. While the turn-over frequency (TOFmax) and turn-over number (TON) are relatively low (TOFmax = 57 mmolH2 molPS-1 min-1; TON(44 h) = 134 mmolH2 molPS-1), the catalytic system is long-lived, losing only 20% of its activity over the course of 12 days. Interestingly, the heteroleptic design in III-C1 proves to be beneficial for the performance as PS, despite III-C1 having comparable photophysical and electrochemical properties as the homoleptic complex IV-C2 (TOFmax = 35 mmolH2 molPS-1 min-1; TON(24 h) = 14 mmolH2 molPS-1). Reductive quenching of the excited PS by the SED is identified as rate-limiting step in both cases.
Hence, the ligands are designed to be more electron-accepting either via N-methylation of the peripheral pyridine substituents or introduction of a pyrimidine ring in the metal ion receptor, leading to increased excited-state lifetimes (τ = 9–40 ns) and luminescence quantum yields (Φ = 40–400*10-5). However, the more electron-accepting character of the ligands also results in anodically shifted reduction potentials, leading to a lack of driving force for the electron transfer from the reduced PS to the catalyst. Hence, this electron transfer step is found to be a limiting factor to the overall performance of the PS. While higher TOFmax in hydrogen evolution experiments are observed for pyrimidine-containing PS (TOFmax = 300–715 mmolH2 molPS-1 min-1), the longevity for these systems is reduced with half-life times of 2–6 h.
Expansion of the pyrimidine-containing ligands to dinuclear complexes yields a stronger absorptivity (ε = 100–135*103 L mol-1 cm-1), increased luminescence (τ = 90–125 ns, Φ = 210–350*10-5) and can also result in higher TOFmax given sufficient driving force for electron transfer to the catalyst (TOFmax = 1500 mmolH2 molPS-1 min-1). When comparing complexes with similar driving forces, stronger luminescence is reflected in a higher TOFmax. Besides thermodynamic considerations, kinetic effects and electron transfer efficiency are assumed to impact the observed activity in hydrogen evolution. In summary, this work shows that targeted ligand design can make the previously disregarded group of Ru(II) complexes with tridentate ligands attractive candidates for use as PS in photocatalytic hydrogen evolution.
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.
In dieser Arbeit konnte ein weiterer und möglicherweise entscheidender Schritt zur Aufklärung des Kriechmechanismus von Gips gemacht und darauf aufbauend Kriterien, Wege und Strategien aufgezeigt werden, um neue Antikriechmittelsubstanzen zu identifizieren oder vorhandene Kriechmittel gezielt zu verbessern. Die Gültigkeit und Praxistauglichkeit der Kriterien wurde exemplarisch nachgewiesen.
Die Basis der Untersuchungen wurde gelegt mit der Errichtung standardisierter Messaufbauten und Verfahren sowie Parameterauswahl für eine beschleunigte und reproduzierbare Darstellung des Kriechphänomens, wobei zunächst im Abgleich sichergestellt wurde, dass das beschleunigte Phänomen mit dem langsam über einen Zeitraum von Jahren erzeugten Phänomen deckungsgleich ist. Darauf aufbauend wurden innovative Untersuchungsmethoden entwickelt, um das Kriechverhalten zu charakterisieren und qualitativ sowie quantitativ zu analysieren. Hierzu wurde zunächst ein Aufbau und eine Messroutine entwickelt und eingeführt, um morphologische Veränderungen während des Kriechvorgangs im Rasterelektronenmikroskop nachzuverfolgen. Im Weiteren wurden Versuchsaufbauten für statische 3-Punkt-Biegeversuche in verschiedenen Lösungen realisiert und diese ergebnisabhängig optimiert. Hierdurch konnte der Einfluss der Löslichkeit von Gips in den entsprechenden Medien auf das Kriechverhalten untersuchen werden. Mittels Laserscanning-Mikroskop wurden wiederum diese Ergebnisse untermauert. Als vorherrschender Kriechmechanismus von Gips wurde damit das Abgleiten einzelner Gipskristalle bedingt durch einen Lösungs-Abscheide-Mechanismus an Orten hoher mechanischer Belastung identifiziert und bestätigt.