@article{MeiningerBlumSchameletal.2017, author = {Meininger, Susanne and Blum, Carina and Schamel, Martha and Barralet, Jake E. and Ignatius, Anita and Gbureck, Uwe}, title = {Phytic acid as alternative setting retarder enhanced biological performance of dicalcium phosphate cement in vitro}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {558}, doi = {10.1038/s41598-017-00731-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171047}, year = {2017}, abstract = {Dicalcium phosphate cement preparation requires the addition of setting retarders to meet clinical requirements regarding handling time and processability. Previous studies have focused on the influence of different setting modifiers on material properties such as mechanical performance or injectability, while ignoring their influence on biological cement properties as they are used in low concentrations in the cement pastes and the occurrence of most compounds in human tissues. Here, analyses of both material and biological behavior were carried out on samples with common setting retardants (citric acid, sodium pyrophosphate, sulfuric acid) and novel (phytic acid). Cytocompatibility was evaluated by in vitro tests with osteoblastic (hFOB 1.19) and osteoclastic (RAW 264.7) cells. We found cytocompatibility was better for sodium pyrophosphate and phytic acid with a three-fold cell metabolic activity by WST-1 test, whereas samples set with citric acid showed reduced cell number as well as cell activity. The compressive strength (CS) of cements formed with phytic acid (CS = 13 MPa) were nearly equal to those formed with citric acid (CS = 15 MPa) and approximately threefold higher than for other setting retardants. Due to a proven cytocompatibility and high mechanical strength, phytic acid seems to be a candidate replacement setting retardant for dicalcium phosphate cements.}, language = {en} } @article{LiebscherTessmarGroll2020, author = {Liebscher, Julia and Teßmar, Joerg Karl and Groll, J{\"u}rgen}, title = {In Situ Polymer Analogue Generation of Azlactone Functions at Poly(oxazoline)s for Peptide Conjugation}, series = {Macromolecular Chemistry and Physics}, volume = {221}, journal = {Macromolecular Chemistry and Physics}, number = {1}, doi = {10.1002/macp.201900500}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208147}, pages = {1900500}, year = {2020}, abstract = {The physical and chemical stability of peptides for biomedical applications can be greatly enhanced through the conjugation of polymers. A well-known but rather underemployed selective coupling functionality is the azlactone group, which readily reacts with a number of different nucleophiles without the need for activation and the formation of any by-products. For example, azlactone functional polymers are used to react with peptides and proteins, rich in amino and thiol groups, to form polymeric beads for affinity-based column chromatography. So far, side chain functional azlactone polymers have been mainly synthesized by radical polymerization using 2-vinyl-4,4-dimethyl azlactone together with different acrylate monomers. Here, a new azlactone precursor equipped with a functional thiol is presented, which can be attached to any vinyl functional polymer by thiol-ene chemistry. Subsequently, the formation of the reactive azlactone ring can be performed in situ at high conversion rate without the need for illumination. This approach is tested on an azlactone side functional poly(2-oxazoline) by coupling amine containing molecules including a model peptide and is proven via \(^1\)H NMR spectroscopy, IR spectroscopy, as well as HPLC measurements.}, language = {en} } @article{BoehmStahlhutWeichholdetal.2022, author = {B{\"o}hm, Christoph and Stahlhut, Philipp and Weichhold, Jan and Hrynevich, Andrei and Teßmar, J{\"o}rg and Dalton, Paul D.}, title = {The Multiweek Thermal Stability of Medical-Grade Poly(ε-caprolactone) During Melt Electrowriting}, series = {Small}, volume = {18}, journal = {Small}, number = {3}, doi = {10.1002/smll.202104193}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257741}, year = {2022}, abstract = {Melt electrowriting (MEW) is a high-resolution additive manufacturing technology that places unique constraints on the processing of thermally degradable polymers. With a single nozzle, MEW operates at low throughput and in this study, medical-grade poly(ε-caprolactone) (PCL) is heated for 25 d at three different temperatures (75, 85, and 95 °C), collecting daily samples. There is an initial increase in the fiber diameter and decrease in the jet speed over the first 5 d, then the MEW process remains stable for the 75 and 85 °C groups. When the collector speed is fixed to a value at least 10\% above the jet speed, the diameter remains constant for 25 d at 75 °C and only increases with time for 85 and 95 °C. Fiber fusion at increased layer height is observed for 85 and 95 °C, while the surface morphology of single fibers remain similar for all temperatures. The properties of the prints are assessed with no observable changes in the degree of crystallinity or the Young's modulus, while the yield strength decreases in later phases only for 95 °C. After the initial 5-d period, the MEW processing of PCL at 75 °C is extraordinarily stable with overall fiber diameters averaging 13.5 ± 1.0 µm over the entire 25-d period.}, language = {en} } @article{EidmannEwaldBoelchetal.2021, author = {Eidmann, Annette and Ewald, Andrea and Boelch, Sebastian P. and Rudert, Maximilian and Holzapfel, Boris M. and Stratos, Ioannis}, title = {In vitro evaluation of antibacterial efficacy of vancomycin-loaded suture tapes and cerclage wires}, series = {Journal of Materials Science: Materials in Medicine}, volume = {32}, journal = {Journal of Materials Science: Materials in Medicine}, number = {4}, doi = {10.1007/s10856-021-06513-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260089}, pages = {42}, year = {2021}, abstract = {Usage of implants containing antibiotic agents has been a common strategy to prevent implant related infections in orthopedic surgery. Unfortunately, most implants with microbial repellent properties are characterized by accessibility limitations during daily clinical practice. Aim of this in vitro study was to investigate whether suture tapes and cerclage wires, which were treated with vancomycin, show a sustainable antibacterial activity. For this purpose, we used 24 stainless steel wire cerclages and 24 ultra-high molecular weight polyethylene and polyester suture tape test bodies. The test bodies were incubated for 30 min. in 100 mg/ml vancomycin solution or equivalent volumes of 0.9\% NaCl. After measuring the initial solution uptake of the test bodies, antibacterial efficacy via agar diffusion test with Staphylococcus aureus and vancomycin elution tests were performed 1, 2, 3, and 6 days after incubation. Vancomycin-loaded tapes as well as vancomycin-loaded cerclage wires demonstrated increased bacterial growth inhibition when compared to NaCl-treated controls. Vancomycin-loaded tapes showed an additional twofold and eightfold increase of bacterial growth inhibition compared to vancomycin-loaded wires at day 1 and 2, respectively. Elution tests at day 1 revealed high levels of vancomycin concentration in vancomycin loaded tapes and wires. Additionally, the concentration in vancomycin loaded tapes was 14-fold higher when compared to vancomycin loaded wires. Incubating suture tapes and cerclage wires in vancomycin solution showed a good short-term antibacterial activity compared to controls. Considering the ease of vancomycin application on suture tapes or wires, our method could represent an attractive therapeutic strategy in biofilm prevention in orthopedic surgery.}, language = {en} } @article{NoHolzmeisterLuetal.2019, author = {No, Young Jung and Holzmeister, Ib and Lu, Zufu and Prajapati, Shubham and Shi, Jeffrey and Gbureck, Uwe and Zreiqat, Hala}, title = {Effect of Baghdadite Substitution on the Physicochemical Properties of Brushite Cements}, series = {Materials}, volume = {12}, journal = {Materials}, number = {10}, issn = {1996-1944}, doi = {10.3390/ma12101719}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196980}, year = {2019}, abstract = {Brushite cements have been clinically used for irregular bone defect filling applications, and various strategies have been previously reported to modify and improve their physicochemical properties such as strength and injectability. However, strategies to address other limitations of brushite cements such as low radiopacity or acidity without negatively impacting mechanical strength have not yet been reported. In this study, we report the effect of substituting the beta-tricalcium phosphate reactant in brushite cement with baghdadite (Ca\(_3\)ZrSi\(_2\)O\(_9\)), a bioactive zirconium-doped calcium silicate ceramic, at various concentrations (0, 5, 10, 20, 30, 50, and 100 wt\%) on the properties of the final brushite cement product. X-ray diffraction profiles indicate the dissolution of baghdadite during the cement reaction, without affecting the crystal structure of the precipitated brushite. EDX analysis shows that calcium is homogeneously distributed within the cement matrix, while zirconium and silicon form cluster-like aggregates with sizes ranging from few microns to more than 50 µm. X-ray images and µ-CT analysis indicate enhanced radiopacity with increased incorporation of baghdadite into brushite cement, with nearly a doubling of the aluminium equivalent thickness at 50 wt\% baghdadite substitution. At the same time, compressive strength of brushite cement increased from 12.9 ± 3.1 MPa to 21.1 ± 4.1 MPa with 10 wt\% baghdadite substitution. Culture medium conditioned with powdered brushite cement approached closer to physiological pH values when the cement is incorporated with increasing amounts of baghdadite (pH = 6.47 for pure brushite, pH = 7.02 for brushite with 20 wt\% baghdadite substitution). Baghdadite substitution also influenced the ionic content in the culture medium, and subsequently affected the proliferative activity of primary human osteoblasts in vitro. This study indicates that baghdadite is a beneficial additive to enhance the radiopacity, mechanical performance and cytocompatibility of brushite cement}, language = {en} } @article{BruecknerMeiningerGrolletal.2019, author = {Br{\"u}ckner, Theresa and Meininger, Markus and Groll, J{\"u}rgen and K{\"u}bler, Alexander C. and Gbureck, Uwe}, title = {Magnesium Phosphate Cement as Mineral Bone Adhesive}, series = {Materials}, volume = {12}, journal = {Materials}, number = {23}, issn = {1996-1944}, doi = {10.3390/ma12233819}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193052}, year = {2019}, abstract = {Mineral bone cements were actually not developed for their application as bone-bonding agents, but as bone void fillers. In particular, calcium phosphate cements (CPC) are considered to be unsuitable for that application, particularly under moist conditions. Here, we showed the ex vivo ability of different magnesium phosphate cements (MPC) to adhere on bovine cortical bone substrates. The cements were obtained from a mixture of farringtonite (Mg\(_3\)(PO\(_4\))\(_2\)) with different amounts of phytic acid (C\(_6\)H\(_{18}\)O\(_{24}\)P\(_6\), inositol hexaphosphate, IP6), whereas cement setting occurred by a chelation reaction between Mg\(^{2+}\) ions and IP6. We were able to show that cements with 25\% IP6 and a powder-to-liquid ratio (PLR) of 2.0 g/mL resulted in shear strengths of 0.81 ± 0.12 MPa on bone even after 7 d storage in aqueous conditions. The samples showed a mixed adhesive-cohesive failure with cement residues on the bone surface as indicated by scanning electron microscopy and energy-dispersive X-ray analysis. The presented material demonstrated appropriate bonding characteristics, which could enable a broadening of the mineral bone cements' application field to bone adhesives}, language = {en} } @article{WeisShanKuhlmannetal.2018, author = {Weis, Matthias and Shan, Junwen and Kuhlmann, Matthias and Jungst, Tomasz and Tessmar, J{\"o}rg and Groll, J{\"u}rgen}, title = {Evaluation of hydrogels based on oxidized hyaluronic acid for bioprinting}, series = {Gels}, volume = {4}, journal = {Gels}, number = {4}, issn = {2310-2861}, doi = {10.3390/gels4040082}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197600}, pages = {82}, year = {2018}, abstract = {In this study, we evaluate hydrogels based on oxidized hyaluronic acid, cross-linked with adipic acid dihydrazide, for their suitability as bioinks for 3D bioprinting. Aldehyde containing hyaluronic acid (AHA) is synthesized and cross-linked via Schiff Base chemistry with bifunctional adipic acid dihydrazide (ADH) to form a mechanically stable hydrogel with good printability. Mechanical and rheological properties of the printed and casted hydrogels are tunable depending on the concentrations of AHA and ADH cross-linkers.}, language = {en} } @article{BakirciFrankGumbeletal.2021, author = {Bakirci, Ezgi and Frank, Andreas and Gumbel, Simon and Otto, Paul F. and F{\"u}rsattel, Eva and Tessmer, Ingrid and Schmidt, Hans-Werner and Dalton, Paul D.}, title = {Melt Electrowriting of Amphiphilic Physically Crosslinked Segmented Copolymers}, series = {Macromolecular Chemistry and Physics}, volume = {222}, journal = {Macromolecular Chemistry and Physics}, number = {22}, doi = {10.1002/macp.202100259}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257572}, year = {2021}, abstract = {Various (AB)\(_{n}\) and (ABAC)\(_{n}\) segmented copolymers with hydrophilic and hydrophobic segments are processed via melt electrowriting (MEW). Two different (AB)\(_{n}\) segmented copolymers composed of bisurea segments and hydrophobic poly(dimethyl siloxane) (PDMS) or hydrophilic poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) (PPO-PEG-PPO) segments, while the amphiphilic (ABAC)\(_{n}\) segmented copolymers consist of bisurea segments in the combination of hydrophobic PDMS segments and hydrophilic PPO-PEG-PPO segments with different ratios, are explored. All copolymer compositions are processed using the same conditions, including nozzle temperature, applied voltage, and collector distance, while changes in applied pressure and collector speed altered the fiber diameter in the range of 7 and 60 µm. All copolymers showed excellent processability with MEW, well-controlled fiber stacking, and inter-layer bonding. Notably, the surfaces of all four copolymer fibers are very smooth when visualized using scanning electron microscopy. However, the fibers show different roughness demonstrated with atomic force microscopy. The non-cytotoxic copolymers increased L929 fibroblast attachment with increasing PDMS content while the different copolymer compositions result in a spectrum of physical properties.}, language = {en} } @article{KadeOttoLuxenhoferetal.2021, author = {Kade, Juliane C. and Otto, Paul F. and Luxenhofer, Robert and Dalton, Paul D.}, title = {Melt electrowriting of poly(vinylidene difluoride) using a heated collector}, series = {Polymers for Advanced Technologies}, volume = {32}, journal = {Polymers for Advanced Technologies}, number = {12}, issn = {1042-7147}, doi = {10.1002/pat.5463}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318493}, pages = {4951 -- 4955}, year = {2021}, abstract = {Previous research on the melt electrowriting (MEW) of poly(vinylidene difluoride) (PVDF) resulted in electroactive fibers, however, printing more than five layers is challenging. Here, we investigate the influence of a heated collector to adjust the solidification rate of the PVDF jet so that it adheres sufficiently to each layer. A collector temperature of 110°C is required to improve fiber processing, resulting in a total of 20 fiber layers. For higher temperatures and higher layers, an interesting phenomenon occurred, where the intersection points of the fibers coalesced into periodic spheres of diameter 206 ± 52 μm (26G, 150°C collector temperature, 2000 mm/min, 10 layers in x- and y-direction).The heated collector is an important component of a MEW printer that allows polymers with a high melting point to be processable with increased layers.}, language = {en} } @article{DoryabTaskinStahlhutetal.2021, author = {Doryab, Ali and Taskin, Mehmet Berat and Stahlhut, Philipp and Schr{\"o}ppel, Andreas and Orak, Sezer and Voss, Carola and Ahluwalia, Arti and Rehberg, Markus and Hilgendorff, Anne and St{\"o}ger, Tobias and Groll, J{\"u}rgen and Schmid, Otmar}, title = {A Bioinspired in vitro Lung Model to Study Particokinetics of Nano-/Microparticles Under Cyclic Stretch and Air-Liquid Interface Conditions}, series = {Frontiers in Bioengineering and Biotechnology}, volume = {9}, journal = {Frontiers in Bioengineering and Biotechnology}, issn = {2296-4185}, doi = {10.3389/fbioe.2021.616830}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223830}, year = {2021}, abstract = {Evolution has endowed the lung with exceptional design providing a large surface area for gas exchange area (ca. 100 m\(^{2}\)) in a relatively small tissue volume (ca. 6 L). This is possible due to a complex tissue architecture that has resulted in one of the most challenging organs to be recreated in the lab. The need for realistic and robust in vitro lung models becomes even more evident as causal therapies, especially for chronic respiratory diseases, are lacking. Here, we describe the Cyclic In VItro Cell-stretch (CIVIC) "breathing" lung bioreactor for pulmonary epithelial cells at the air-liquid interface (ALI) experiencing cyclic stretch while monitoring stretch-related parameters (amplitude, frequency, and membrane elastic modulus) under real-time conditions. The previously described biomimetic copolymeric BETA membrane (5 μm thick, bioactive, porous, and elastic) was attempted to be improved for even more biomimetic permeability, elasticity (elastic modulus and stretchability), and bioactivity by changing its chemical composition. This biphasic membrane supports both the initial formation of a tight monolayer of pulmonary epithelial cells (A549 and 16HBE14o\(^{-}\)) under submerged conditions and the subsequent cell-stretch experiments at the ALI without preconditioning of the membrane. The newly manufactured versions of the BETA membrane did not improve the characteristics of the previously determined optimum BETA membrane (9.35\% PCL and 6.34\% gelatin [w/v solvent]). Hence, the optimum BETA membrane was used to investigate quantitatively the role of physiologic cyclic mechanical stretch (10\% linear stretch; 0.33 Hz: light exercise conditions) on size-dependent cellular uptake and transepithelial transport of nanoparticles (100 nm) and microparticles (1,000 nm) for alveolar epithelial cells (A549) under ALI conditions. Our results show that physiologic stretch enhances cellular uptake of 100 nm nanoparticles across the epithelial cell barrier, but the barrier becomes permeable for both nano- and micron-sized particles (100 and 1,000 nm). This suggests that currently used static in vitro assays may underestimate cellular uptake and transbarrier transport of nanoparticles in the lung.}, language = {en} }