bims-orenst 2022-05-22 papers

Issue of 2022‒05‒22
six papers selected by
Joram Mooiweer
University of Groningen

Med (N Y). 2021 Jan 15. pii: S2666-6340(20)30082-9. [Epub ahead of print]2(1): 16-18

An Organ-on-a-Chip System to Study Anaerobic Bacteria in Intestinal Health and Disease.

A state-of-the-art organ-on-a-chip system enabled co-culture of highly oxygen-sensitive Faecalibacterium prausnitzii with human intestinal epithelial cells, recapitulating a critical role of the bacteria in the maintenance of anti-inflammatory phenotype of gut epithelium mediated by bacteria-secreted butyrate.

DOI: https://doi.org/10.1016/j.medj.2020.12.016

Front Bioeng Biotechnol. 2022 ;10 877480

A Facile Method for Generating a Smooth and Tubular Vessel Lumen Using a Viscous Fingering Pattern in a Microfluidic Device.

Ting-Yuan Tu, Yen-Ping Shen, Sei-Hien Lim, Yang-Kao Wang.

Blood vessels are ubiquitous in the human body and play essential roles not only in the delivery of vital oxygen and nutrients but also in many disease implications and drug transportation. Although fabricating in vitro blood vessels has been greatly facilitated through various microfluidic organ-on-chip systems, most platforms that are used in the laboratories suffer from a series of laborious processes ranging from chip fabrication, optimization, and control of physiologic flows in micro-channels. These issues have thus limited the implementation of the technique to broader scientific communities that are not ready to fabricate microfluidic systems in-house. Therefore, we aimed to identify a commercially available microfluidic solution that supports user custom protocol developed for microvasculature-on-a-chip (MVOC). The custom protocol was validated to reliably form a smooth and functional blood vessel using a viscous fingering (VF) technique. Using VF technique, the unpolymerized collagen gel in the media channels was extruded by less viscous fluid through VF passive flow pumping, whereby the fluid volume at the inlet and outlet ports are different. The different diameters of hollow tubes produced by VF technique were carefully investigated by varying the ambient temperature, the pressure of the passive pump, the pre-polymerization time, and the concentration of collagen type I. Subsequently, culturing human umbilical vein endothelial cells inside the hollow structure to form blood vessels validated that the VF-created structure revealed a much greater permeability reduction than the vessel formed without VF patterns, highlighting that a more functional vessel tube can be formed in the proposed methodology. We believe the current protocol is timely and will offer new opportunities in the field of in vitro MVOC.

Keywords: HUVECs; microfluidics; microvasculature; permeability coefficient; viscous fingering

DOI: https://doi.org/10.3389/fbioe.2022.877480

Front Pharmacol. 2022 ;13 837261

An in silico Model of T Cell Infiltration Dynamics Based on an Advanced in vitro System to Enhance Preclinical Decision Making in Cancer Immunotherapy.

Thomas D Lewin, Blandine Avignon, Alessio Tovaglieri, Lauriane Cabon, Nikolche Gjorevski, Lucy G Hutchinson.

Cancer immunotherapy often involves the use of engineered molecules to selectively bind and activate T cells located within tumour tissue. Fundamental to the success of such treatments is the presence or recruitment of T cells localised within the tumour microenvironment. Advanced organ-on-a-chip systems provide an in vitro setting in which to investigate how novel molecules influence the spatiotemporal dynamics of T cell infiltration into tissue, both in the context of anti-tumour efficacy and off-tumour toxicity. While highly promising, the complexity of these systems is such that mathematical modelling plays a crucial role in the quantitative evaluation of experimental results and maximising the mechanistic insight derived. We develop a mechanistic, mathematical model of a novel microphysiological in vitro platform that recapitulates T cell infiltration into epithelial tissue, which may be normal or transformed. The mathematical model describes the spatiotemporal dynamics of infiltrating T cells in response to chemotactic cytokine signalling. We integrate the model with dynamic imaging data to optimise key model parameters. The mathematical model demonstrates a good fit to the observed experimental data and accurately describes the distribution of infiltrating T cells. This model is designed to complement the in vitro system; with the potential to elucidate complex biological mechanisms, including the mode of action of novel therapies and the drivers of safety events, and, ultimately, improve the efficacy-safety profile of T cell-targeted cancer immunotherapies.

Keywords: T cell infiltration; cancer immunotherapy; in vitro cell systems; mathematical modelling; spatio—temporal analysis

DOI: https://doi.org/10.3389/fphar.2022.837261

Biomater Sci. 2022 May 16.

A 3D printable perfused hydrogel vascular model to assay ultrasound-induced permeability.

Madison K Royse, A Kristen Means, Gisele A Calderon, Ian S Kinstlinger, Yufang He, Marc R Durante, Adam T Procopio, Omid Veiseh, Jun Xu.

The development of an in vitro model to study vascular permeability is vital for clinical applications such as the targeted delivery of therapeutics. This work demonstrates the use of a perfusion-based 3D printable hydrogel vascular model as an assessment for endothelial permeability and its barrier function. Aside from providing a platform that more closely mimics the dynamic vascular conditions in vivo, this model enables the real-time observation of changes in the endothelial monolayer during the application of ultrasound to investigate the downstream effect of ultrasound-induced permeability. We show an increase in the apparent permeability coefficient of a fluorescently labeled tracer molecule after ultrasound treatment via a custom MATLAB algorithm, which implemented advanced features such as edge detection and a dynamic region of interest, thus supporting the use of ultrasound as a non-invasive method to enhance vascular permeability for targeted drug therapies. Notably, live-cell imaging with VE-cadherin-GFP HUVECs provides some of the first real-time acquisitions of the dynamics of endothelial cell-cell junctions under the application of ultrasound in a 3D perfusable model. This model demonstrates potential as a new scalable platform to investigate ultrasound-assisted delivery of therapeutics across a cellular barrier that more accurately mimics the physiologic matrix and fluid dynamics.

DOI: https://doi.org/10.1039/d2bm00223j

Front Pharmacol. 2022 ;13 871569

Direct Contraction Force Measurements of Engineered Cardiac Tissue Constructs With Inotropic Drug Exposure.

Maria Koivisto, Milad Mosallaei, Tarja Toimela, Sampo Tuukkanen, Tuula Heinonen.

Contractility is one of the most crucial functions of the heart because it is directly related to the maintenance of blood perfusion throughout the body. Both increase and decrease in contractility may cause fatal consequences. Therefore, drug discovery would benefit greatly from reliable testing of candidate molecule effects on contractility capacity. In this study, we further developed a dual-axis piezoelectric force sensor together with our human cell-based vascularized cardiac tissue constructs for cardiac contraction force measurements. The capability to detect drug-induced inotropic effects was tested with a set of known positive and negative inotropic compounds of isoprenaline, milrinone, omecamtiv mecarbil, propranolol, or verapamil in different concentrations. Both positive and negative inotropic effects were measurable, showing that our cardiac contraction force measurement system including a piezoelectric cantilever sensor and a human cell-based cardiac tissue constructs has the potential to be used for testing of inotropic drug effects.

Keywords: cardiac tissue model; conformal coating; contraction force; force measurement; human-induced pluripotent stem cell–derived cardiomyocytes; in vitro model; inotropic drug

DOI: https://doi.org/10.3389/fphar.2022.871569

Sensors (Basel). 2022 Apr 21. pii: 3191. [Epub ahead of print]22(9):

Surface Optimization and Design Adaptation toward Spheroid Formation On-Chip.

Neda Azizipour, Rahi Avazpour, Mohamad Sawan, Abdellah Ajji, Derek H Rosenzweig.

Spheroids have become an essential tool in preclinical cancer research. The uniformity of spheroids is a critical parameter in drug test results. Spheroids form by self-assembly of cells. Hence, the control of homogeneity of spheroids in terms of size, shape, and density is challenging. We developed surface-optimized polydimethylsiloxane (PDMS) biochip platforms for uniform spheroid formation on-chip. These biochips were surface modified with 10% bovine serum albumin (BSA) to effectively suppress cell adhesion on the PDMS surface. These surface-optimized platforms facilitate cell self-aggregations to produce homogenous non-scaffold-based spheroids. We produced uniform spheroids on these biochips using six different established human cell lines and a co-culture model. Here, we observe that the concentration of the BSA is important in blocking cell adhesion to the PDMS surfaces. Biochips treated with 3% BSA demonstrated cell repellent properties similar to the bare PDMS surfaces. This work highlights the importance of surface modification on spheroid production on PDMS-based microfluidic devices.

Keywords: 3D cell culture; PDMS; cancer; microfluidic; spheroid; surface modification

DOI: https://doi.org/10.3390/s22093191