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AUTHOR Kajtez, Janko and Buchmann, Sebastian and Vasudevan, Shashank and Birtele, Marcella and Rocchetti, Stefano and Pless, Christian Jonathan and Heiskanen, Arto and Barker, Roger A. and Martínez-Serrano, Alberto and Parmar, Malin and Lind, Johan Ulrik and Emnéus, Jenny
Title 3D-Printed Soft Lithography for Complex Compartmentalized Microfluidic Neural Devices [Abstract]
Year 2020
Journal/Proceedings Advanced Science
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Abstract Compartmentalized microfluidic platforms are an invaluable tool in neuroscience research. However, harnessing the full potential of this technology remains hindered by the lack of a simple fabrication approach for the creation of intricate device architectures with high-aspect ratio features. Here, a hybrid additive manufacturing approach is presented for the fabrication of open-well compartmentalized neural devices that provides larger freedom of device design, removes the need for manual postprocessing, and allows an increase in the biocompatibility of the system. Suitability of the method for multimaterial integration allows to tailor the device architecture for the long-term maintenance of healthy human stem-cell derived neurons and astrocytes, spanning at least 40 days. Leveraging fast-prototyping capabilities at both micro and macroscale, a proof-of-principle human in vitro model of the nigrostriatal pathway is created. By presenting a route for novel materials and unique architectures in microfluidic systems, the method provides new possibilities in biological research beyond neuroscience applications.
AUTHOR Kajtez, Janko and Wesseler, Milan Finn and Birtele, Marcella and Khorasgani, Farinaz Riyahi and Rylander Ottosson, Daniella and Heiskanen, Arto and Kamperman, Tom and Leijten, Jeroen and Martínez-Serrano, Alberto and Larsen, Niels B. and Angelini, Thomas E. and Parmar, Malin and Lind, Johan U. and Emnéus, Jenny
Title Embedded 3D Printing in Self-Healing Annealable Composites for Precise Patterning of Functionally Mature Human Neural Constructs [Abstract]
Year 2022
Journal/Proceedings Advanced Science
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Abstract Human in vitro models of neural tissue with tunable microenvironment and defined spatial arrangement are needed to facilitate studies of brain development and disease. Towards this end, embedded printing inside granular gels holds great promise as it allows precise patterning of extremely soft tissue constructs. However, granular printing support formulations are restricted to only a handful of materials. Therefore, there has been a need for novel materials that take advantage of versatile biomimicry of bulk hydrogels while providing high-fidelity support for embedded printing akin to granular gels. To address this need, Authors present a modular platform for bioengineering of neuronal networks via direct embedded 3D printing of human stem cells inside Self-Healing Annealable Particle-Extracellular matrix (SHAPE) composites. SHAPE composites consist of soft microgels immersed in viscous extracellular-matrix solution to enable precise and programmable patterning of human stem cells and consequent generation mature subtype-specific neurons that extend projections into the volume of the annealed support. The developed approach further allows multi-ink deposition, live spatial and temporal monitoring of oxygen levels, as well as creation of vascular-like channels. Due to its modularity and versatility, SHAPE biomanufacturing toolbox has potential to be used in applications beyond functional modeling of mechanically sensitive neural constructs.
AUTHOR Azim, N. and Hart, C. and Sommerhage, F. and Aubin, M. and Hickman, J. J. and Rajaraman, S.
Title Precision Plating of Human Electrogenic Cells on Microelectrodes Enhanced With Precision Electrodeposited Nano-Porous Platinum for Cell-Based Biosensing Applications [Abstract]
Year 2019
Journal/Proceedings Journal of Microelectromechanical Systems
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Microelectrode Arrays are established platforms for biosensing applications; however, limitations in electrode impedance and cell-electrode coupling still exist. In this paper, the SNR of 25 μm diameter gold (Au) microelectrodes was improved by decreasing the impedance with precision electrodeposition. SEM determined that N-P Pt. microelectrodes had nanoporous structures that filled the insulation cylinders. EIS, CV, and RMS noise measurements concluded that the optimized electrodeposition of N-P Pt. led to a lowered impedance of 18.36 kΩ ± 2.6 kΩ at 1 kHz, a larger double layer capacitance of 73 nF, and lowered RMS noise of 2.08±0.16 μV as compared to the values for Au of 159 kΩ ± 28 kΩ at 1 kHz, 17nF, and 3.14 ± 0.42 μV, respectively. Human motoneurons and human cardiomyocytes were cultured on N-P Pt. devices to assess their biocompatibility and signal quality. In order to improve the cell-electrode coupling, a precision plating technique was used. Both cell types were electrically active on devices for up to 10 weeks, demonstrated improved SNR, and expected responses to precision chemical and electrical stimulation. The modification of Au microelectrodes with nanomaterials in combination with precision culturing of human cell types provides cost effective, highly sensitive, well coupled and relevant biosensing platforms for medical and pharmaceutical research.
AUTHOR Li, Jianfeng and Hietel, Benjamin and Brunk, Michael G. K. and Reimers, Armin and Willems, Christian and Groth, Thomas and Cynis, Holger and Adelung, Rainer and Schütt, Fabian and Sacher, Wesley D. and Poon, Joyce K. S.
Title 3D-printed microstructured alginate scaffolds for neural tissue engineering [Abstract]
Year 2024
Journal/Proceedings Trends in Biotechnology
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Tetrapod-shaped ZnO (t-ZnO) microparticles create interconnected channels and textured surfaces in 3D-printed microstructured alginate (M-Alg) scaffolds.Primary mouse cortical neurons cultured on the M-Alg scaffolds demonstrate enhanced adhesion and maturation, with formation of extensive 3D neural projections, indicating the potential of this scaffold design for advanced neural tissue engineering applications.
AUTHOR Tung, Yen-Ting and Chen, Yu-Chi and Derr, Kristy and Wilson, Kelli and Song, Min Jae and Ferrer, Marc
Title A 3D Bioprinted Human Neurovascular Unit Model of Glioblastoma Tumor Growth [Abstract]
Year 2024
Journal/Proceedings Advanced Healthcare Materials
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Abstract A 3D bioprinted neurovascular unit (NVU) model was developed to study glioblastoma (GBM) tumor growth in a brain-like microenvironment. The NVU model included human primary astrocytes, pericytes and brain microvascular endothelial cells, and patient-derived glioblastoma cells (JHH-520) were used for this study. We used fluorescence reporters with confocal high content imaging to quantitate real-time microvascular network formation and tumor growth. Extensive validation of the NVU-GBM model included immunostaining for brain relevant cellular markers and extracellular matrix components; single cell RNA sequencing to establish physiologically relevant transcriptomics changes; and secretion of NVU and GBM-relevant cytokines. The scRNAseq revealed changes in gene expression and cytokines secretion associated with wound healing/angiogenesis, including the appearance of an endothelial mesenchymal transition (EndMT) cell population. The NVU-GBM model was used to test 18 chemotherapeutics and anti-cancer drugs to assess the pharmacological relevance of the model and robustness for high throughput screening. This article is protected by copyright. All rights reserved