Biomimetic microvasculature-on-a-chip for drug screening applications

Jyotsana Priyadarshani’s interview with Bio Patrika hosting “Vigyan Patrika”, a series of author interviews. Jyotsana completed her B.Tech. and M.E. both in Biomedical Engineering from JIS college of Engineering, WBUT and Jadavpur University (JU) respectively. She worked with Prof. Himadri Chattopadhyay, JU for her M.E. thesis in hemorheology. Currently, she is pursuing her PhD in the area of “organ-on-a-chip” under the supervision of Prof Soumen Das & Prof Suman Chakraborty at SMST, IIT Kharagpur. Her research focuses on utilizing the frugal fabrication technique and microfluidic applications to address the important features and geometrical complexities of microvasculature in vitro. Such bioengineered microfluidic platforms are potentially suitable for probing cellular dynamics as well as offering critical insights into cancer, cardiovascular diseases, offsetting the requirements of in vivo trials on animals and humans to a large extent. Here, Jyotsana talks about her work titled “Transport of vascular endothelial growth factor dictates on-chip angiogenesis in tumor microenvironment” published as the first author in Physics of Fluids journal.

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How would you explain your paper’s key results to the non-scientific community?

Human physiology is very complex. In our circulatory system, for example, the blood vessels form a transportation network throughout the body to ensure the supply of oxygen and vital nutrients to each cell, “the basic unit of life”. This orchestrated circulation, however, may be severely disrupted under different diseased conditions. Cancer, being one of those conditions, creates a very complicated surrounding around the tumour by engaging nearby blood vessels, affecting the regions in immediate vicinity of the diseased cells as well as the molecules that may potentially exchange information with them. While drugs targeted to specific affected cells may be administered, thanks to outstanding technological advancement in the said field, the complexity of the surroundings around the diseased location may deviate the pathway of the drug from its desired target in real clinical practice. Testing the efficacy of targeted drug delivery before administering into human patients, therefore, becomes extremely critical in pre-clinical trials. Often, such testing is organized on other animals, which may be otherwise challenged not just because of ethical considerations but also for the fact that the relevant physiology in humans and other animals may have subtle decisive distinctions. Of late, human-microvasculature mimicking devices have emerged to offer artificially-engineered drug-testing platforms. Our paper advances the design of such tumour-on-a-chip platform by replicating the mechanism of angiogenesis, i.e., the emergence of new blood vessels from the pre-existing ones. In this process, we developed a simulation platform that can capture the movement of cells under chemical gradients produced by tumours, directional motility of cells, growth of micro- blood vessels and their fusion at different physiological conditions. Our results decipher the mechanism of interaction between a tumour and its immediate surroundings which acts as a key to ensure effective protocols of targeting drug molecules to a specific location at the diseased site.

Figure 1. Schematic representation showing conventional drug development stages and advantages of microfluidic technology; (a) hierarchical complex vascular network, (b) phenomena of angiogenic sprouting from a healthy blood vessel in the presence of tumour cells (c) blood vessel section, (d) layers of blood vessel wall showing inner layer is formed of endothelium which interacts with blood flow; inset figure shows biomimicking of angiogenesis on a microfluidic platform.

“The findings will allow us to design artificially engineered “organ-on-a-chip” platforms that closely mimic the functionalities of human body micro-circulation in healthy and diseased conditions.”

What are the possible consequences of these findings for your research area?

The findings will allow us to design artificially engineered “organ-on-a-chip” platforms that closely mimic the functionalities of human body micro-circulation in healthy and diseased conditions. In the field of drug discovery and cell biology research, laboratories and other industries are extensively dependent on traditional animal-based studies or static 2D/3D cell cultures that have no resemblance to the human physiological environment. The present study will open up new possibilities of developing extremely advanced bio-mimetic devices that may be used as synthetic simulators of human body ambience for drug discovery, drug delivery and cell biology research.

What was the exciting moment (eureka moment) during your research?

While the concept of bio-mimicking device development remains exciting as ever. One key bottleneck remained to be the use of sophisticated manufacturing and laboratory practice for their advancement towards real-life applications. Our eureka moment in this journey struck when we could organize extremely frugal resources to build such a platform and further modify it to mimic the physiology of micro-circulation environment around a tumour in line with reported medical studies. Such a disruptive approach of making tumour-microenvironment mimicking devices in limited-resource settings is likely to revolutionize R&D of the healthcare industry.

What do you hope to do next?

We hope to perform pre-clinical and clinical studies around advancement of this platform, to address specific perspectives of cancer research including movement of circulatory tumour cells, cancer metastasis and efficacy of targeted drugs.

 Where do you seek scientific inspiration?

The inspiration came from the idea of ‘animal-free clinical research’. Creating a bio-mimetic platform itself towards that endeavour is very adventurous as Mother Nature is the best engineer of all. One of her finest architecture is the complex vascular network in our body, which is interlaced with each and every organ of our body. Thus, bio-mimicking such hierarchical vascular network and associated pathology using microfluidic technology and conventional tissue-culture tools is very fascinating and exciting.

How do you intend to help Indian science improve?

We would like to contribute in the area of biomimetic fabrication of such organ-on-a-chip platform to a next level where we can collaborate with pharmaceutical industries to fasten the process of drug development by bridging the gap between pre-clinical trials and clinical trials. These organ-on-a-chip platforms need more scientific awareness, especially in India as it holds great potential to revolutionize the healthcare industry by curbing the sky-soaring cost of drug development and minimize use of animal models.

Reference

Jyotsana Priyadarshani, Prasoon Awasthi, Pratyaksh Karan, Soumen Das, and Suman Chakraborty. Transport of vascular endothelial growth factor dictates on-chip angiogenesis in tumor microenvironment. Physics of Fluids; 33, 031910 (2021) https://doi.org/10.1063/5.0042487

Email: srivastava.jyoti67@gmail.com

Dr. Suman Chakraborty lab: https://sites.google.com/site/sumanchakrabortymicrofluidics/home

Edited by: Pragya Gupta (Copy Editor, Volunteer, Biopatrika)

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