BioBot Beta Publications
This publication from Dr. Ali Khademhosseini’s Lab in Lab on a Chip constructs a biomimetic thrombosis-on-a-chip model with pluronic, GelMA and a BioBot Beta.
Abstract: Thrombosis and its complications are among the most prevalent medical problems. Despite advancements in medical therapies, there is often incomplete resolution of these issues. The residual thrombus can undergo fibrotic changes over time through invaded fibroblasts from the surrounding tissues and eventually lead to the formation of a permanent clot. In order to understand the importance of cellular interactions and the impact of potential therapeutics to treat thrombosis, an in vitro platform using human cells and blood components would be beneficial. Towards achieving this aim, there have been studies utilizing the capabilities of microdevices to study the hemodynamics associated with thrombosis. In this work, we have further exploited the utilization of 3D bioprinting technology, for the construction of a highly biomimetic thrombosis-on-a-chip model. The model consisted of microchannels coated with a layer of confluent human endothelium embedded in a gelatin methacryloyl (GelMA) hydrogel, where human whole blood was infused and induced to form thrombi. Continuous perfusion with tissue plasmin activator led to dissolution of non-fibrotic clots, revealing clinical relevance of the model. Further encapsulating fibroblasts in the GelMA matrix demonstrated the potential migration of these cells into the clot and subsequent deposition of collagen type I over time, facilitating fibrosis remodeling that resembles the in vivo scenario. Our study suggests that in vitro 3D bioprinted blood coagulation models can be used to study the pathology of fibrosis, and particularly, in thrombosis. This versatile platform may be conveniently extended to other vascularized fibrosis models.
Zhang, Y. Shrike, et al. “Bioprinted Thrombosis-on-a-Chip.” Lab on a Chip(2016).
Dual-Stage Crosslinking of a Gel-Phase Bioink Improves Cell Viability and Homogeneity for 3D Bioprinting
This paper, recently published in Advanced Healthcare Materials by Professor Sarah C. Heilshorn’s lab at Stanford University, utilizes a BioBot Beta to develop a novel bioink hydrogel.
Abstract: Current bioinks for cell-based 3D bioprinting are not suitable for technology scale-up due to the challenges of cell sedimentation, cell membrane damage, and cell dehydration. A novel bioink hydrogel is presented with dual-stage crosslinking specifically designed to overcome these three major hurdles. This bioink enables the direct patterning of highly viable, multicell type constructs with long-term spatial fidelity.
Dubbin, K., Hori, Y., Lewis, K. K. and Heilshorn, S. C. (2016), Dual-Stage Crosslinking of a Gel-Phase Bioink Improves Cell Viability and Homogeneity for 3D Bioprinting. Advanced Healthcare Materials. doi: 10.1002/adhm.201600636
This publication in Biofabrication by Dr. Kara Spiller’s lab at Drexel University utilizes a BioBot Beta to analyze and compare mechanical and swelling properties of gelatin methacrylate hydrogels prepared with conventional molding techniques and 3D printing.
Abstract: The mechanical properties of hydrogels used in biomaterials and tissue engineering applications are critical determinants of their functionality. Despite the recent rise of additive manufacturing, and specifically extrusion-based bioprinting, as a prominent biofabrication method, comprehensive studies investigating the mechanical behavior of extruded constructs remain lacking. To address this gap in knowledge, we compared the mechanical properties and swelling properties of crosslinked gelatin-based hydrogels prepared by conventional molding techniques or by 3D bioprinting using a BioBots Beta pneumatic extruder. A preliminary characterization of the impact of bioprinting parameters on construct properties revealed that both Young’s modulus and optimal extruding pressure increased with polymer content, and that printing resolution increased with both printing speed and nozzle gauge. High viability (>95%) of encapsulated NIH 3T3 fibroblasts confirmed the cytocompatibility of the construct preparation process. Interestingly, the Young’s moduli of extruded and molded constructs were not different, but extruded constructs did show increases in both the rate and extent of time-dependent mechanical behavior observed in creep. Despite similar polymer densities, extruded hydrogels showed greater swelling over time compared to molded hydrogels, suggesting that differences in creep behavior derived from differences in microstructure and fluid flow. Because of the crucial roles of time-dependent mechanical properties, fluid flow, and swelling properties on tissue and cell behavior, these findings highlight the need for greater consideration of the effects of the extrusion process on hydrogel properties.
N Ersumo, C E Witherel and K L Spiller. “Differences in Time-Dependent Mechanical Properties Between Extruded and Molded Hydrogels,” Biofabrication. 8(3).