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Future Trends in Biomedical Applications
Published in Savaş Kaya, Sasikumar Yesudass, Srinivasan Arthanari, Sivakumar Bose, Goncagül Serdaroğlu, Materials Development and Processing for Biomedical Applications, 2022
Somasundaram Ambiga, Raja Suja Pandian, Abdul Bakrudeen Ali Ahmed, Raju Ramasubbu, Ramu Arun Kumar, Lazarus Vijune Lawrence, Arjun Pandian, Sasikumar Yesudass, Sivakumar Bose
A different forum for medicine development is Organ-on-a-chip (OOc). OOc is also called a micro-physiological system. Organ-on-a-chip is a biomimetic system and tiny device (i.e. a physiological organ built on a microfluidic chip). Approximately one billion people across the world have struggled from neurodegenerative disorders, like Parkinson’s disease and Alzheimer’s (AD), according to the World Health Organization (WHO) (Batista et al. 2004). An OOc combines various disciplines of material, chemical and biological sciences. The aim for the invention is to simulate the human organs’ physiological roles, activities and mechanics (Lutolf et al. 2003). Organ-on-a-chip can mimic the human organs. It has the ability in the regulation of key parameters which includes tissue boundaries, cell patterning, shear force, concentration gradients, and tissue-organ interactions. These chips are designed for the purpose of controlling the physiological functions of the organs, and to control the fluid flow and viability of the cell. They are also important for the identification of any dysfunction of the body (ASTM 2003).
Nanotechnology in Preventive and Emergency Healthcare
Published in Bhaskar Mazumder, Subhabrata Ray, Paulami Pal, Yashwant Pathak, Nanotechnology, 2019
Nilutpal Sharma Bora, Bhaskar Mazumder, Manash Pratim Pathak, Kumud Joshi, Pronobesh Chattopadhyay
The mere presence of blood flow marks the availability of a dynamic environment along with the added benefit of mechanical stimuli, which cannot be found in usual cell culture-based in vitro systems. The cellular microenvironment in living cells is often heterogeneous, whereas cell culture-based screening systems are usually constructed on homogeneous substrates, which restricts the showcasing of the efficacy of a drug candidate in the human body, where interactions between multiple organs exist (Lee and Sung, 2013). The failure of two-dimensional (2D) cell culture in reconstituting the cellular microenvironment lead to the development of 3D cell culture models, which allow cells to grow within extracellular matrix (ECM) gels (Huh et al., 2011). But 3D cell culture models also failed in some respects, such as the highly variable sizes and shapes of organs and, within the structures, the inability to maintain the positions of cells consistently. The lack of fluid flow in the model has put a question mark on the interaction of cultured cells with the circulating blood cells as well as the immune cells. Organ-on-a-chip systems are micrometer-sized chambers, which are perfused with miniature microfluidic devices for culturing living cells, that mimic the physiological functions of organs and tissues. The aim of this procedure is to develop the minimum number of functional units that can copy tissue systems or an organ as a whole. A prime example of the simplest unit of an organ-on-a-chip model is a perfused, single microfluidic assembly containing a single kind of cultured cell (Bhatia, 2014).
Nanotechnology for Tissue Engineering and Regenerative Medicine
Published in Šeila Selimovic, Nanopatterning and Nanoscale Devices for Biological Applications, 2017
Şükran Şeker, Y. Emre Arslan, Serap Durkut, A. Eser Elçin, Y. Murat Elçin
Organ-on-a-chip systems are being used for tissue engineering and drug development studies. Huh et al. developed an actual lung-on-a-chip microfluidic device that reproduces the critical structural, functional, and mechanical properties of the human alveolar–capillary interface, which is the basic functional unit of the living lung [101]. In this study, two of the channels fabricated by soft lithography were separated by a thin (10 μm), porous, flexible membrane made of PDMS. This membrane was coated with ECM proteins (fibronectin or collagen). Then, human alveolar epithelial cells and human pulmonary microvascular endothelial cells were cultured on opposite sides of the ECM-coated membrane (Figure 14.15). The cellular response to a pulmonary infection of bacterial origin and to silica nanoparticles was demonstrated using this system. The results indicated that the developed lung-on-a-chip microfluidic device could reconstitute multiple physiological functions observed in the whole living lung. These findings have shown that this bioinspired microdevice may enhance the capabilities of cell culture models and allow low-cost alternatives to animal and clinical studies for drug screening and toxicology studies [101].
Assessing the in vitro toxicity of airborne (nano)particles to the human respiratory system: from basic to advanced models
Published in Journal of Toxicology and Environmental Health, Part B, 2023
Maria João Bessa, Fátima Brandão, Fernanda Rosário, Luciana Moreira, Ana Teresa Reis, Vanessa Valdiglesias, Blanca Laffon, Sónia Fraga, João Paulo Teixeira
Mechanically active microdevices, named organ-on-a-chip, combining the capability of cell culture models with microfluidics were developed to (1) reconstitute tissue-tissue interfaces crucial to resemble organ functions, and (2) are gaining relevance for drug screening and toxicology applications. The ideal lung-on-a-chip needs to encompass a micro engineered cell culture device capable of replicating the human lung 3D architecture, environment, breathing movement, and physiology. The first lung-on-a-chip was reported by Huh et al. (2010), who developed a biomimetic microsystem replicating key structural, functional, and mechanical properties of the human alveolar-capillary interface. This model consisted of a microfluidic system with two microchannels separated by a thin, flexible and porous membrane coated with fibronectin or collagen to resemble the ECM, and human alveolar epithelial and pulmonary microvascular endothelial cells cultured on opposite sides of the membrane (Figure 3e). This biologically inspired human breathing lung-on-a-chip microdevice has been successfully used to evaluate SiO2 NP transport across this in vitro alveolar-capillary barrier, intracellular ROS production, and inflammatory responses (Huh et al. 2010). To simulate in vivo environment of the alveolar space and gas exchange conditions, epithelial cells were exposed at the ALI. After exposure to SiO2 NP aerosols it was observed that : (1) high levels of intercellular adhesion molecule (ICAM)-1 expression from the underlying endothelium cells; (2) increased endothelial capture of circulating neutrophils, promotion of their migration across the permeable membrane (tissue-tissue interface), and accumulation onto epithelial surface; (3) simulated physiological “breathing” by mechanical forces; (4) enhanced absorption of SiO2 NP from the airspace to the microvascular channel; (5) accentuated pro-inflammatory activities and development of acute lung inflammation; and (6) a steady rise in ROS production (Huh 2015; Huh et al. 2010).
Emerging applications of microfluidic techniques for in vitro toxicity studies of atmospheric particulate matter
Published in Aerosol Science and Technology, 2021
Fobang Liu, Nga Lee Ng, Hang Lu
The developments of microengineering approaches for 3D cell culture have been further improved to reconstitute 3D organ-level structures. Various organ-on-a-chip models have been constructed on microfluidic platforms, which recapitulate biochemical and mechanical microenvironments, in addition to having a 3D matrix for cell growth (Huh, Hamilton, and Ingber 2011). For example, in lung-on-a-chip models, air is introduced into the epithelial channel to mimic the air-liquid interface within the lung. The respiratory tract is a major route for airborne PM to enter human body. There have been a few studies using lung-on-a-chip models to evaluate the pulmonary risk of PM exposure in an organotypic manner (Huh et al. 2010; Xu et al. 2020; Zheng et al. 2019). In the model developed by Huh et al. (2010), in addition to 3D cell culture, two lateral microchambers were incorporated into the device to simulate dynamic mechanical distortion of the alveolar-capillary interface caused by breathing movements. This lung-on-a-chip model was used to study the toxicology of silica nanoparticles. Results indicate that cyclic mechanical strain contributes to the activation of pro-inflammatory activities of silica nanoparticles. Mechanical strain also enhances epithelial and endothelial uptake of nanoparticles and stimulates their transport into the underlying microvascular channel. Similarly, Xu et al. (2020) employed a lung-on-a-chip model to probe the adverse effects of ambient PM in the respiratory system (Figure 5B). The model enables investigating multiple cellular responses (e.g., ROS generation, apoptosis, and inflammatory cytokines expression) and cell-cell interactions (e.g., changes of adherens junctions and permeability of the alveolar-capillary barrier) induced by PM. Further, immunocytes could be introduced to the vessel channel forming a triple coculture system to investigate the interaction of injured tissue and immunocytes. Interestingly, an increase in permeability of the alveolar‐capillary barrier was observed in both the studies of Xu et al. (2020) and Huh et al. (2010), although different microfluidic designs and PM samples were tested in the two studies. These complexities in the tissue model could potentially push the relevance of the in vitro system toward better mimicking the physiology in vivo.