Modern Problems Require Modern SoC-lutions
Nanomedicine Research Group, ICTMumbai
Nanomedicine Research Group at ICT is doing disruptive research in the area of applied biotechnology
Presentations by the PhD scholars? of NRG were initiated by the 4th year Ph.D. scholar, Mr. Advait Bhagwat , who is bioprinting a 3-D skin model for use in preclinical testing during drug development.?
When a researcher wishes to study a disease in controlled conditions or when a new treatment developed for a disease is to be tested, its safety and efficacy are evaluated in suitable ‘models’, which are representations of human systems. Testing in models helps researchers extrapolate the results that may be achieved in humans. The most well-known models are animals- insects, fish, rodents and many more. While animal models tell researchers how a treatment or disease looks like in a living organism or under in vivo conditions, ethical guidelines limit the extent to which animals may be used. Sometimes, the way in which a? drug gets metabolised in an animal model differs so much from the way it would get metabolised in a human that drugs that are toxic or ineffective in humans get approved for clinical trials, while drugs that would be effective in humans get rejected solely due to poor performance in animal models.
Thus, researchers are now preferring to use cell cultures- living, growing and proliferating cells of human origin in controlled, in-vitro conditions. While cell-based models are more ethical than animal models, traditional 2-dimensional (single layer) cell cultures are not representative of the 3-dimensional nature of human organ systems. Furthermore, in a 2-D cell culture, all cells grow and proliferate more or less to the same extent, unlike under in vivo conditions, where cells are at different growth stages.?
One of the ways in which researchers can overcome these challenges is by using three-dimensional cell cultures. These are in-vitro cultures of cells that are a better representative of an organ system. Unlike a 2D cell culture, 3D cell cultures allow researchers to study conditions where cells can differentiate and organise themselves like they would in-vivo. These conditions are created using micro-assembled structures and complex environmental parameters. 3-D cell cultures used currently can be spheroids and organs-on-chips, amongst others.
Organs-on-chips or OoCs are models that replicate complex, 3-D and naturally occurring organ systems in microscope slide-like chips. It is a microengineered biometric system that is able to mimic the structural and functional characteristics of a human tissue. How does it do so? An OoC contains microchannels that can guide small volumes of fluids like media and drug systems. The channels themselves can also be lined with the cells of organs and blood vessels. This mimics the way tissues would interact with each other in a living system. Many OoC models have already been developed so far, such as the lung-on-a-chip, brain-on-a-chip, skin-on-a-chip, heart-on-a-chip, gut-on-a-chip and more.
NRG Ph.D. scholar Advait Bhagwat is working on creating an OoC modelled after skin or skin-on-chip (SoC), that can be used for preclinical testing. He believes that his microfluidic device will imitate in-vivo conditions well, can be visualised easily and is comparable to human skin equivalents or HSEs found in the market. Throughout his PhD? project, he aimed to first develop the SoC device and then develop and characterise the bioink used to print it. In the later stages of the project, he performed viability studies on the bioprinted SoC and then characterised it.?
Advait started the meeting by sharing his progress so far- including the patenting of one of his early designs for the SoC. He also shared his progress on bioink optimisation, rheological characterisation, compression testing, static culture-viability testing, seeding co-cultures of cells into his device and trans-epithelial electrical resistance (TEER) measurement. Further, he plans to introduce one more type of cell into his device, perform cell-tracking experiments, high-content imaging and immunostaining.
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The work of Advait and all the other researchers working on OoCs can revolutionise clinical testing as they miniaturise a biological system and allow control of parameters such as concentration gradients, fluid shear stress and organ-organ interactions. By using OoCs, drug discovery becomes easier with respect to hit-to-lead optimisation, pharmacokinetic studies, toxicological studies and phenotypic screening. We wish Advait all the best for his research!
Written by Sanjana Krishnakumar (Science Communicator) and edited by Dr. Prajakta Dandekar (Principal Investigator) Nanomedicine Research Group, ICTMumbai
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