Vast Potentials of Microphysiological Systems
Tata Institute of Fundamental Research, Mumbai
With a growing need in the biomedical field, it is imminent to find the best of model systems to address basic and translational questions. For decades, 2D cultures have been used immensely, for disease modelling studies to test drugs for diseases. However, they often do not resemble the actual physiological complexities of the heterogeneous tissues and organs. Hence, over time, several labs are working towards finding better microscale realistic models of organs. Spheroids, organoids, bioprinted tissue patches/organs and microfluidic MPS have become some of the more advanced model systems that can recapitulate human organs/ tissues anatomically and functionally.
Spheroids are cell aggregates that are majorly derived from a single cell type (immortalised cell lines or primary cells) and are grown on a scaffold-free platform. These clusters are formed in low-adhesion media, by hanging-drop techniques, or spinning bioreactors, in which the cells adhere together. Spheroids have a small culture size and also require limited resources, hence have found immense usage in high-throughput fast screening of drugs, embryoid bodies, glands, and tumoroids. However, they lack the power of self-(re) organisation or regeneration as in native tissues. On the other hand, organoids, which are formed from cells of a tissue, embryonic stem cells or induced pluripotent stem cells, and built on scaffolds, can re-organize to form higher-order patterns. They can also be expanded, cryopreserved, and genetically modified. It is also possible to combine associated cells to the organoid culture and build more advanced level complicated tissue/organ micro-scale systems. Additionally, the architecture, shape, size, structure and composition of organoids can be modulated based on the tissue/organ of interest by controlling their environment, viz., scaffold pattern, media, growth factors, shear flow, etc. Thus, possibilities of organoids range from modelling parts of gut, liver, heart, kidney, brain and various cancers to name a few. These models have been useful for pharmacology, toxicology, oncology and immuno-oncology, and infectious disease studies and have also been used to maintain organoid biobanks. However, intra- and inter-batch variabilities in the spatial arrangement of cells in organoids have caused significant problems with reproducibility and questioned their fitness for clinical applications.
Some of these challenges can now be resolved by constructing 3D-bioprinted tissues where specific characteristics of the actual target tissues can be used for designing the bioprinted model. Newer techniques of bioprinting are also enabling the construction of intricate vascular systems as well as temporally controllable dynamic biomimetic structures (by using smart biomaterials). Currently, bioprinted organs range from skin tissue to bone, cartilage, vascular structures, etc.
Even though more advanced organ/organoid models described above could spatio-temporally resemble actual tissues/ organs, there are still some drawbacks. Larger organ models develop necrotic cores due to lack of nutrients pertaining to poor diffusivity in large spherical structures. Thus, organoids have been integrated into microfluidic chips to allow formation of perfusion channels for supplying nutrients, removing excretes, etc. These microfluidic systems also help in monitoring drug delivery or metabolic analysis. Implanted-sensor mediated in-situ monitoring is also being developed recently. In addition, the field is currently also working towards modelling the crosstalk between organs by interconnecting multiple organ models. Such wholesome systems are at its infancy, but hold a huge potential to build organ models retaining the identity of integrated human organs. Some of these models have already found uses for drug testing against COVID-19, influenza, cystic fibrosis disorders, etc.
With progressive advancement of biomaterials and biofabrication, along with newer technologies and ongoing impressive investigations, will eventually lead to more holistic microphysiological systems that can transform the biomedical field with more clinical applications. Some exciting possible outcomes will include better regenerative treatments, improved understanding of disease mechanisms, better and targeted therapies for cancer, drug designing, screening, predictive modelling, and personalised medicines.