TY - THES A1 - Ryma, Matthias T1 - Exploiting the Thermoresponsive Properties of Poly(2-oxazoline)s for Biofabrication T1 - Anwendung der Thermoresponsivität von Poly(2-oxazolin) für die Biofabrikation N2 - In this thesis, non-modified POx, namely PnPrOx and PcycloPrOx, with an LCST in the physiological range between 20 and 37°C have been utilized as materials for three different biofabrication approaches. Their thermoresponsive behavior and processability were exploited to establish an easy-to-apply coating for cell sheet engineering, a novel method to create biomimetic scaffolds based on aligned fibrils via Melt Electrowriting (MEW) and the application of melt electrowritten sacrificial scaffolds for microchannel creation for hydrogels. Chapter 3 describes the establishment of a thermoresponsive coating for tissue culture plates. Here, PnPrOx was simply dissolved in water and dried in well plates and petri dishes in an oven. PnPrOx adsorbed to the surface, and the addition of warm media generated a cell culture compatible coating. It was shown that different cell types were able to attach and proliferate. After confluency, temperature reduction led to the detachment of cell sheets. Compared to standard procedures for surface coating, the thermoresponsive polymer is not bound covalently to the surface and therefore does not require specialized equipment and chemical knowledge. However, it should be noted that the detachment of the cell layer requires the dissolution of the PnPrOx-coating, leading to possible polymer contamination. Although it is only a small amount of polymer dissolved in the media, the detached cell sheets need to be washed by media exchange for further processing if required. ... N2 - In dieser Dissertation wurden die unmodifizierten Poly(2-oxazoline) PnPrOx und PcycloProx, welche eine LCST im physiologischen Bereich zwischen 20 und 37°C aufweisen, für drei verschiedene Biofabrikationsansätze verwendet. Deren Thermoresponsivität und Prozessierbarkeit wurde genutzt, um ein simples Beschichten von Oberflächen für Cell Sheet Engineering, eine neue Methode zur Herstellung biomimetischer Gerüststrukturen basierend auf der Generierung von Fibrillenbündeln via Melt Electrowriting und die Anwendung als Opferstrukturen zur Generierung von Mikrokanälen in Hydrogelen zu etablieren. KW - Thermoresponsive Polymere KW - Dihydrooxazole KW - 3D-Druck KW - Melt Electrowriting KW - Biofabrikation KW - Poly(2-oxazoline) KW - Cell Sheet Engineering KW - Vaskularisation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-247462 ER - TY - JOUR A1 - Ryma, Matthias A1 - Genç, Hatice A1 - Nadernezhad, Ali A1 - Paulus, Ilona A1 - Schneidereit, Dominik A1 - Friedrich, Oliver A1 - Andelovic, Kristina A1 - Lyer, Stefan A1 - Alexiou, Christoph A1 - Cicha, Iwona A1 - Groll, Jürgen T1 - A Print-and-Fuse Strategy for Sacrificial Filaments Enables Biomimetically Structured Perfusable Microvascular Networks with Functional Endothelium Inside 3D Hydrogels JF - Advanced Materials N2 - A facile and flexible approach for the integration of biomimetically branched microvasculature within bulk hydrogels is presented. For this, sacrificial scaffolds of thermoresponsive poly(2-cyclopropyl-2-oxazoline) (PcycloPrOx) are created using melt electrowriting (MEW) in an optimized and predictable way and subsequently placed into a customized bioreactor system, which is then filled with a hydrogel precursor solution. The aqueous environment above the lower critical solution temperature (LCST) of PcycloPrOx at 25 °C swells the polymer without dissolving it, resulting in fusion of filaments that are deposited onto each other (print-and-fuse approach). Accordingly, an adequate printing pathway design results in generating physiological-like branchings and channel volumes that approximate Murray's law in the geometrical ratio between parent and daughter vessels. After gel formation, a temperature decrease below the LCST produces interconnected microchannels with distinct inlet and outlet regions. Initial placement of the sacrificial scaffolds in the bioreactors in a pre-defined manner directly yields perfusable structures via leakage-free fluid connections in a reproducible one-step procedure. Using this approach, rapid formation of a tight and biologically functional endothelial layer, as assessed not only through fluorescent dye diffusion, but also by tumor necrosis factor alpha (TNF-α) stimulation, is obtained within three days. KW - hydrogels KW - microvasculature KW - melt electrowriting Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318532 VL - 34 IS - 28 ER - TY - JOUR A1 - Nadernezhad, Ali A1 - Ryma, Matthias A1 - Genç, Hatice A1 - Cicha, Iwona A1 - Jüngst, Thomasz A1 - Groll, Jürgen T1 - Melt electrowriting of isomalt for high‐resolution templating of embedded microchannels JF - Advanced Material Technologies N2 - Fabrication of microchannels using 3D printing of sugars as fugitive material is explored in different fields, including microfluidics. However, establishing reproducible methods for the controlled production of sugar structures with sub-100 μm dimensions remains a challenge. This study pioneers the processing of sugars by melt electrowriting (MEW) enabling the fabrication of structures with so far unprecedented resolution from Isomalt. Based on a systematic variation of process parameters, fibers with diameters down to 20 μm can be fabricated. The flexibility in the adjustment of fiber diameter by on-demand alteration of MEW parameters enables generating constructs with perfusable channels within polydimethylsiloxane molds. These channels have a diameter that can be adjusted from 30 to 200 μm in a single design. Taken together, the experiments show that MEW strongly benefits from the thermal and physical stability of Isomalt, providing a robust platform for the fabrication of small-diameter embedded microchannel systems. KW - medicine KW - sugar glass printing KW - embedded templating KW - melt electrowriting KW - microfibers KW - microfluidics KW - sacrificial printing Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256401 VL - 6 IS - 8 ER - TY - JOUR A1 - Ryma, Matthias A1 - Tylek, Tina A1 - Liebscher, Julia A1 - Blum, Carina A1 - Fernandez, Robin A1 - Böhm, Christoph A1 - Kastenmüller, Wolfgang A1 - Gasteiger, Georg A1 - Groll, Jürgen T1 - Translation of collagen ultrastructure to biomaterial fabrication for material-independent but highly efficient topographic immunomodulation JF - Advanced materials N2 - Supplement-free induction of cellular differentiation and polarization solely through the topography of materials is an auspicious strategy but has so far significantly lagged behind the efficiency and intensity of media-supplementation-based protocols. Consistent with the idea that 3D structural motifs in the extracellular matrix possess immunomodulatory capacity as part of the natural healing process, it is found in this study that human-monocyte-derived macrophages show a strong M2a-like prohealing polarization when cultured on type I rat-tail collagen fibers but not on collagen I films. Therefore, it is hypothesized that highly aligned nanofibrils also of synthetic polymers, if packed into larger bundles in 3D topographical biomimetic similarity to native collagen I, would induce a localized macrophage polarization. For the automated fabrication of such bundles in a 3D printing manner, the strategy of “melt electrofibrillation” is pioneered by the integration of flow-directed polymer phase separation into melt electrowriting and subsequent selective dissolution of the matrix polymer postprocessing. This process yields nanofiber bundles with a remarkable structural similarity to native collagen I fibers, particularly for medical-grade poly(ε-caprolactone). These biomimetic fibrillar structures indeed induce a pronounced elongation of human-monocyte-derived macrophages and unprecedentedly trigger their M2-like polarization similar in efficacy as interleukin-4 treatment. KW - biofabrication KW - extracellular matrix KW - immunomodulation KW - macrophages KW - melt electrofibrillation KW - melt electrowriting Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256381 VL - 33 IS - 33 ER -