Publikationsliste Fritz Koch

• Originalarbeiten in wissenschaftlichen Fachzeitschriften
• Konferenzbeiträge

Originalarbeiten in wissenschaftlichen Fachzeitschriften

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2023

• J. Weygant, F. Koch, K. Adam, K. Tröndle, R. Zengerle, G. Finkenzeller, S. Kartmann, P. Koltay, S. Zimmermann
  A Drop-on-Demand Bioprinting Approach to Spatial Arrangement of Multiple Cell Types and Monitoring Their Cell–Cell Interactions towards Vascularization Based on Endothelial Cells and Mesenchymal Stem Cells
  2023 Cells, Band: 12, Nummer: 4, Seite: 646

2022

• K. Tröndle, G. Miotto, L. Rizzo, R. Pichler, F. Koch, P. Koltay, R. Zengerle, S. S. Lienkamp, S. Kartmann, S. Zimmermann
  Deep Learning-Assisted Nephrotoxicity Testing with Bioprinted Renal Spheroids
  2022 Int. J. Bioprint, Band: 8, Nummer: 2, Seite: 528
• V. Burchak, F. Koch, L. Siebler, S. Haase, V. K. Horner, X. Kempter, G. B. Stark, U. Schepers, A. Grimm, S. Zimmermann, P. Koltay, S. Strassburg, G. Finkenzeller, F. Simunovic, F. Lampert
  Evaluation of a Novel Thiol–Norbornene-Functionalized Gelatin Hydrogel for Bioprinting of Mesenchymal Stem Cells
  2022 Int. J. Mol. Sci., Band: 23, Seite: 7939
• F. Koch, O. Thaden, S. Conrad, K. Tröndle, G. Finkenzeller, R. Zengerle, S. Kartmann, S. Zimmermann, P. Koltay
  Mechanical properties of polycaprolactone (PCL) scaffolds for hybrid 3D-bioprinting with alginate-gelatin hydrogel
  2022 J. Mech. Behav. Biomed. Mat., Band: 130, Seite: 105219

2021

• F. Koch, O. Thaden, K. Tröndle, R. Zengerle, S. Zimmermann, P. Koltay
  Open-source hybrid 3D-bioprinter for simultaneous printing of thermoplastics and hydrogels
  2021 HardwareX, Band: 10, Seite: e00230

2020

• F. Koch, K. Tröndle, G. Finkenzeller, R. Zengerle, S. Zimmermann, P. Koltay
  Generic method of printing window adjustment for extrusion-based 3D-bioprinting to maintain high viability of mesenchymal stem cells in an alginate-gelatin hydrogel
  2020 Bioprinting, Seite: e00094
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  Kurzfassung

  Over the last decade, bioprinting of artificial tissues has been developed into a significant field of research. With an increasing number of printing technologies and bioinks used in bioprinting, its complexity increases as both the printing technology and the properties of the bioink influence the cell biological functionality and printing accuracy of the printed tissue. Therefore, optimization of bioprinting processes often remains a challenge, which could be solved by a smart fine-tuning of the process parameters. We present a novel method to adjust the printing window for extrusion-based bioprinting on the basis of a two-step assessment to determine process parameters such as nozzle size, extrusion flow rate, and printing temperature. First, a suitable printing temperature is deduced from the bioink properties and second nozzle size and extrusion flow rate is selected in a way that the immediate cell damage after printing is reduced. For both steps only basic rheological properties of the bioinks need to be known as well as detailed knowledge of the cell survival in the bioink for different shear stresses. This method is applied to an exemplary alginate-gelatin hydrogel to show how the printing temperature affects the achievable printing accuracy. For this bioink, viability of immortalized mesenchymal stem cells (iMSC) decreases with about 4% per thousand Pascal increase in maximum shear stress. For different combinations of flow rate, nozzle size and nozzle shape it is shown, that only the maximum shear stress experienced by the iMSCs influences average cell viability. Factors like flow rate, nozzle size and shape only play an indirect role by influencing the maximum shear stress and individually have no significant influence on cell viability. The experimental results allow a direct adjustment of printing parameters for the presented combination of hydrogel and cell type but are not limited to it. For other bioinks, the described generic method can be easily used to systematically adjust the printing parameters. For this purpose, only the basic rheological properties and the influence of shear stress on cell survival need to be known and process parameters can be set concerning the respective application.
• P. Rukavina, F. Koch, M. Wehrle, K. Tröndle, G. B. Stark, P. Koltay, S. Zimmermann, R. Zengerle, F. Lampert, S. Strassburg, G. Finkenzeller, F. Simunovic
  In vivo evaluation of bioprinted prevascularized bone tissue
  2020 Biotechnol Bioeng, Seiten: 1 - 10
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  Kurzfassung

  Bioprinting can be considered as a progression of the classical tissue engineering approach, in which cells are randomly seeded into scaffolds. Bioprinting offers the advantage that cells can be placed with high spatial fidelity within three‐dimensional tissue constructs. A decisive factor to be addressed for bioprinting approaches of artificial tissues is that almost all tissues of the human body depend on a functioning vascular system for the supply of oxygen and nutrients. In this study, we have generated cuboid prevascularized bone tissue constructs by bioprinting human adipose‐derived mesenchymal stem cells (ASCs) and human umbilical vein endothelial cells (HUVECs) by extrusion‐based bioprinting and drop‐on‐demand (DoD) bioprinting, respectively. The computer‐generated print design could be verified in vitro after printing. After subcutaneous implantation of bioprinted constructs in immunodeficient mice, blood vessel formation with human microvessels of different calibers could be detected arising from bioprinted HUVECs and stabilization of human blood vessels by mouse pericytes was observed. In addition, bioprinted ASCs were able to synthesize a calcified bone matrix as an indicator of ectopic bone formation. These results indicate that the combined bioprinting of ASCs and HUVECs represents a promising strategy to produce prevascularized artificial bone tissue for prospective applications in the treatment of critical‐sized bone defects.

2019

• K. Tröndle, F. Koch, G. Finkenzeller, G. B. Stark, R. Zengerle, P. Koltay, S. Zimmermann
  Bioprinting of high cell density constructs leads to controlled lumen formation with self‐assembly of endothelial cells
  2019 Journal of Tissue Engineering and Regenerative Medicine, Band: 13, Nummer: 10, Seiten: 1883 - 1895
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  Kurzfassung

  Active nutrient supply and waste product removal are key requirements for the fabrication of long term viable and functional tissue constructs of considerable size. This work aims to contribute to the fabrication of artificial perfusable networks with a bioprinting process, based on drop‐on‐demand (DoD) printing of primary endothelial cell (EC) suspension bioink (25 · 106 ± 3 · 106 cells/ml). The process results in prescribed lumen between two hydrogel layers, allowing its integration in common layering based bioprinting processes. Low volume bioink droplets (appr. 10 nl) as building blocks, were deposited between two fibrin or collagen I layers to realize shapeable, cell‐rich aggregates. Unattainable with manual positioning, DoD printing allowed precise fabrication of various designs, such as spheroidal‐, line‐shaped and Y‐branch cellular structures, with a mean lateral extension of 285 ± 81 μm. For basic characterization, the cell suspension building blocks were systematically compared to preformed spheroids of the same cell type, passage and number. Post printing investigations of initially loose cell arrangements showed self‐assembly and formation of central lumen with a mean cross‐sectional area of Ølumen = 6400 μm2 at day 3, lined by a single layer of CD31 positive ECs, as evaluated by confocal microscopy. Originating from this main lumen smaller, undirected side‐branches (Øbranches = 740 μm2) were formed by sprouting cells, inducing a first step towards a simplistic hierarchically organized network. These lumen could prospectively help for tissue construct perfusion in vitro or, potentially, as niche for angiogenesis of host vascularization in implants.
• M. Wehrle, F. Koch, S. Zimmermann, P. Koltay, R. Zengerle, G. B. Stark, S. Strassburg, G. Finkenzeller
  Examination of Hydrogels and Mesenchymal Stem Cell Sources for Bioprinting of Artificial Osteogenic Tissues
  2019 Cellular and Molecular Bioengineering, Seiten: 1 - 15
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  Kurzfassung

  Mesenchymal stem cells (MSCs) represent a very important cell source in the field of regenerative medicine and for bone and cartilage tissue engineering applications. Three-dimensional (3D) bioprinting has the potential to improve the classical tissue engineering concept as this technique allows the printing of cells with high spatial control of cell allocation within a 3D construct. In this study, we systematically compared different hydrogel blends for 3D bioprinting of MSCs by testing their cytocompatibility, ability to support osteogenic differentiation and their mechanical properties. In addition, we compared four different MSC populations isolated from different human tissues for their osteogenic differentiation capacity in combination with different hydrogels. The aim of this study was to identify the best MSC source and the most suitable hydrogel blend for extrusion-based bioprinting of 3D large-scaled osteogenic constructs.

2016

• S. Kartmann, F. Koch, P. Koltay, R. Zengerle, A. Ernst
  Single-use capacitive pressure sensor employing radial expansion of a silicone tube
  2016 Sensor Actuat A-phys, Band: 247
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  Kurzfassung

  This paper reports on a single-use pressure sensor for medical applications. The sensor principle makes use of the radial expansion of a silicone tube which occurs when there is a pressure difference between the inside and the outside of the tube. The change in outer diameter is detected by a capacitive measurement method, whereas the amplification electronics can be separated from the tube being in contact with the fluid. This enables a cross-contamination-free measurement system for patient near application as e.g. within infusion systems. The sensor includes a novel highly sensitive and fast analog amplification circuit in combination with gold electrodes fabricated in PCB technology. This circuit enables to amplify even highly dynamic pressure changes, in the range of a few milliseconds causing capacitive changes on the electrodes in the fF range to a readable voltage level. A functional model is developed based on flex board technology which allows for studying the influence of the electrode geometry as well as the material properties of the silicone tube with respect to the sensitivity of the sensor. The best performing electrode geometry determined by experiments features a sensitivity of 0.195 fF/kPa at a mean coefficient of variation (CV) of 6.4%, considering three individual sensor assemblies. A sensor prototype is designed and fabricated based on the results of the investigated functional model. The performance of the prototype is investigated experimentally in a pressure range from 0 to 40 kPa. As a result a sensitivity of 0.135 V/kPa for DI water as measurement liquid could be achieved and a good linearity of the signal (R² = 0.996) was observed up to 35 kPa.

Konferenzbeiträge

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2022

• L. Riek, F. Koch, D. Frejek, L. Zausch, R. Zengerle, P. Koltay, S. Kartmann, S. Zimmermann
  A Bioprinting Fidelity Imager (BioFI) for a standardized characterization of bioprinting processes
  2022 SLAS Europe 2022 Conference and Exhibition, Dublin, Ireland, May 26, 2022
• F. Koch, L. Riek, D. Frejek, L. Zausch, S. Zimmermann, S. Kartmann, R. Zengerle, A. Osorio-Madrazo, P. Koltay
  Towards standardized characterization of droplet-based bioprinting processes
  2022 Biofabrication 2022, Pisa, Italy, September, 25-28, 2022

2021

• J. Weygant, F. Koch, K. Troendle, G. Finkenzeller, R. Zengerle, S. Kartmann, S. Zimmermann, P. Koltay
  Drop-on-Demand Bioprinting Approach For Precise Alignment and Interaction Studies of Different Cell Types
  2021 International Conference on Biofabrication, Australia, 27. – 29.09.2021 (online)
• K. Tröndle, A. Itani, F. Koch, R. Zengerle, P. Koltay, S. Zimmermann
  Drop-on-demand bioprinting solutions for the fabrication of 3D cell culture systems
  2021 DECHEMA 3D Cell Culture Freiburg (online), 05.-07.05.2021
• F. Koch, K. Tröndle, G. Finkenzeller, P. Rukavina, R. Zengerle, P. Koltay, S. Zimmermann
  Hybrider 3D-Biodruck zur künstlichen Herstellung von Knochen / Using hybrid processes for 3D-bioprinting of artificial bone tissue
  2021 MST-Kongress, Ludwigsburg, 08.-10.11.2021

2020

• K. Tröndle, A. Itani, F. Koch, R. Zengerle, S. Zimmermann, P. Koltay
  Fabrication and fluidic integration of self-assembled cellular microtubules for nephron-on-chip applications
  2020 MicroTAS 2020, 04.-09.10.2020, virtual

2019

• F. Koch, M. Wehrle, K. Tröndle, P. Koltay, G. Finkenzeller, R. Zengerle, S. Zimmermann
  Rapid assessment of combined drop on demand and extrusion-based bioprinting with controlled shear stress and high shape fidelity
  2019 Transducers 2019 - EUROSENSORS XXXIII 23. -27. Juni 2019 - Berlin, Germany
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  Kurzfassung

  We present a novel combination of drop on demand (DoD) and extrusion-based bioprinting to generate highprecision patterns of cells inside large hydrogel volumes. Extrusion-based bioprinting has the great advantage of enabling a fast deposition of high viscous cell-loaded hydrogel with reasonable precision. Compromises between high shape fidelity and cell viability, as well as short process times often require many iterations of optimizing process parameters and varying compositions of the hydrogel. To limit the multitude of parameters during extrusion-based bioprinting, a method for rapid process assessment was developed. This enables to define limits for printing temperature, flow rate and nozzle size from basic rheological measurements with regard to the biological and mechanical requirements. The combination of extrusion-based bioprinting with DoD bioprinting allows for precise deposition of low viscous cell suspension and adjustable concentrations of crosslinking agent. Together, the technologies were used to print a bone replacement model by using the predefined process parameters. Adiposed-derived stem cells (ASC) prone to osteogenic differentiation were homogenously extruded in a cuboid structure of 10x10x5 mm. Human umbilical vein endothelial cells (HUVEC) were printed as highly dense cell suspension lines inside the extruded hydrogel to allow a potential vascularization of the structure in vivo.
• F. Koch, M. Wehrle, K. Tröndle, P. Koltay, G. Finkenzeller, R. Zengerle, S. Zimmermann
  Rapid assessment of extrusion based bioprinting by controlling shear stresses on cells
  2019 Transducers 2019, Berlin, 23.06. - 27.06.2019

2017

• S. Kartmann, F. Koch, A. Ernst, R. Zengerle, P. Koltay
  A single-use in-line flow sensor fore closed-loop controlled precise non-contact liquid dispensing
  2017 MFHS, Twente / The Netherlands, 04. - 06.10.2017
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  Kurzfassung

  This paper reports on a closed-loop controlled non-contact liquid dispensing system. The system employs a control algorithm and consists of a single-use in-line flow sensor and a disposable electromagnetic dispensing valve. By measuring the flow rate in real time, the system can control the opening time of the valve and is thus able to react to potential environmental influences such as pressure or temperature fluctuations. Furthermore, the system has the advantage that all fluid-carrying components can be exchanged after use, therefore cost intensive cleaning steps can be avoided. The precision of the system was demonstrated experimentally for different volumes in the range of 2:8 ml to 4:9 ml. The resulting coefficient of variation (CV) was below 2 %.
• S. Zimmermann, J. Schoendube, A. Gross, B. Steimle, L. Lautscham, K. Pfleghar, T. Christmann, B. Werdelmann, F. Koch, J. Riba, P. Koltay, R. Zengerle, M. Pirsch
  Cell line development by single-cell printing and cell imaging
  2017 Cell Line Development & Engineering, Amsterdam, 23.-25. April 2017
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  Kurzfassung

  In biopharmaceutical production the proof of monoclonality is a regulatory requirement for the development of clonal cell lines. A complementary approach based on a single-cell printer (scp, cytena GmbH) and a NYONE cell imager (SYNENTEC GmbH) is used to produce truly monoclonal cell lines and compared to standard single-cell isolation technologies like limited dilution and FACS. Different CHO cell lines were used on different microtiter plate types in addition to cell-equivalent beads for testing the system.
• S. Kartmann, F. Koch, R. Zengerle, P. Koltay, A. Ernst
  Single-use flow sensor based on the differential pressure principle employing the radial expansion of a low-cost silicone tube
  2017 Transducers 2017, Kaohsiung/Taiwan, 18. – 22.06.2017
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  Kurzfassung

  For the first time, we present a flow sensor consisting of low-cost consumable parts, to minimize the risk of cross-contamination in medical applications, for example. For our sensor, the consumable component consists of two simple silicone tubes and a capillary, which can be exchanged easily and cost-effectively after use. We characterized the flow sensor in the range from 0 up to 50 μL/s. The sensor showed a good consistency with the reference sensor, a linear correlation coefficient of minimal R(x,y) = 0.98 and a sensor resolution of 0.4 μL/s.
• F. Koch, S. Kartmann, R. Zengerle, A. Ernst, P. Koltay
  Viscosity determination by the in-line measurement of liquid flow time through a cylindrical tube
  2017 MFHS, Twente / The Netherlands, 04. - 06.10.2017
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  Kurzfassung

  This paper demonstrates a novel in-line viscosity measurement concept, with reduced effort compared to common approaches. It determines the transition-time of a liquid/gas front to fill a well-defined capillary. In contrast to previous work [1] this paper measures the transition-time for the first time in a non-contact capacitive way. The method enables to determine the dynamic viscosity with a mean coefficient of variation (CV) of 8.4% for a measuring range between 1 and 20 mPa s and showed to be valuable as a fast viscosity calibration for flow sensors using the differential pressure principle.