Abstract
The organ-on-a-chip (OOAC) technology stands at the forefront of emergent technologies, representing a biomimetic configuration of functional organs on a microfluidic chip. This technology synergizes biomedical engineering, cell biology, and biomaterial technology to mimic the microenvironment of specific organs. It effectively replicates the biomechanical and biological soft tissue interfaces, enabling the simulation of organ functionality and responses to various stimuli, including drug reactions and environmental effects. OOAC has vast implications for precision medicine and biological defense strategies. In this chapter, the authors delve into the principles of OOAC, exploring its role in creating physiological models and discussing its advantages, current challenges, and prospects. This examination is significant as it highlights the transformative potential of OOAC technologies in the 21st century and contributes to a deeper understanding of OOAC's applications in advancing medical research.
TopIntroduction
The Organ-on-a-Chip (OOAC) ranks among the top 10 emerging technologies and denotes a biomimetic system of physiological organs constructed within a microfluidic chip (Singh et al., 2022). By amalgamating principles from cell biology, engineering, and biomaterial technology, the chip's microenvironment replicates that of actual organs, encompassing tissue interfaces and mechanical stimulation. This emulation faithfully mirrors the structural and functional traits of human tissue, permitting the anticipation of responses to various stimuli, including drug reactions and environmental influences (Wu et al., 2020). OOAC boasts wide-ranging applications in precision medicine and strategies related to biological defense. The fusion of microfluidics, tissue engineering, and lab-on-a-chip (LOC) technologies has given rise to the nascent concept of OAAC (Arshavsky-Graham & Segal, 2022). This approach employs microscale environments with microchannels and chambers to mimic the natural habitat of human cells (Barua & Datta, 2023a). OOAC offers several advantages over conventional methods, some of which are depicted in Figure 1. The primary material of choice for fabrication is biocompatible polydimethylsiloxane (PDMS) due to its remarkable transparency and elasticity, albeit it possesses limited chemical resistance and can absorb specific organic compounds, drugs, and biomolecules (Campbell et al., 2021; Datta & Barua, 2023). Ongoing developments explore alternative biocompatible materials, such as polymethylmethacrylate (PMMA), which is more cost-effective but less flexible than PDMS. Materials like polystyrene (PS), polycarbonate (PC), polyimide (PI), collagen, gelatin, and alginate have also found utility in fabrication (Barua & Datta, 2023b; van Meer et al., 2017). However, the selection of the appropriate material must account for individual properties such as elasticity, transparency, and chemical resistance.
Figure 1. The benefits of OOAC technology compared to cell cultures and animal models
OOAC's modular nature allows for the incorporation of various modules, including actuators and sensors, for diverse analyses. Compared to existing methods, these modules offer precision and furnish highly pertinent clinical data (Datta et al., 2023). Additionally, OOAC can accommodate multiple layers of cells, reproducing the intricate cellular interactions found in tissues. Interconnection of multiple organs is also feasible, facilitating simultaneous analysis of different organs (Li et al., 2022). The progression of 3D bioprinting and 3D microfabrication techniques has further fueled the growth of OOAC technologies, expanding their applications into personalized medicine, micro-robotics, drug delivery, therapeutics, and more (Barua et al., 2021; Datta et al., 2019). As micro-physiological in vitro modeling hinges on several factors (microfluidics, chip engineering, biomarkers, biomaterials, and cell sources), the advancement of OOAC technology relies on the development of all these domains. Organ-on-a-Chip (OOAC) technology represents a dynamic and swiftly progressing domain of investigation within the realms of tissue engineering and biomedical science (Barua et al., 2023b; Waidi et al., 2023). These Organ-on-a-Chip devices are essentially miniature microfluidic platforms that strive to emulate the physiological and mechanical characteristics of human organs under tightly controlled conditions (Kanabekova et al., 2022). Their potential to transform drug testing, disease modeling, and personalized medicine is immense, offering more precise and pertinent replicas of human organs compared to conventional cell culture methodologies (Maschmeyer et al., 2015).
Key Terms in this Chapter
Vascular Networks: A vascular network refers to the intricate system of blood vessels within the human body, responsible for transporting blood, oxygen, and nutrients to organs and tissues while removing waste products. This network includes arteries that carry oxygenated blood away from the heart, veins that return deoxygenated blood, and capillaries for exchange. Maintaining a healthy vascular network is crucial for overall well-being. Vascular diseases, like atherosclerosis, can disrupt blood flow and lead to serious health issues. Understanding and treating vascular conditions are essential for ensuring proper organ function and overall health.
Lab-on-a-chip (LOC): A technology miniaturizes complex laboratory processes onto tiny, portable devices, typically the size of a credit card. These chips integrate various functions, including sample preparation, analysis, and detection, making them valuable for fields like diagnostics, genomics, and chemical analysis. LOCs offer rapid results, reduced sample volumes, and cost-effective testing. They find applications in healthcare for point-of-care diagnostics and have potential uses in environmental monitoring and food safety. The technology streamlines laboratory procedures, making it a game-changer in analytical chemistry and biotechnology, offering improved efficiency and convenience.
3D Bioprinting: An innovative technology that combines 3D printing with biological materials to create complex living structures like tissues and organs. It holds enormous potential for regenerative medicine and drug testing. By layering bioinks containing living cells, scientists can engineer functional biological constructs, mimicking natural tissues. This technology aids in personalized medicine, allowing the creation of patient-specific implants. Despite ongoing research challenges, 3D bioprinting is a promising avenue for advancing healthcare by providing solutions for organ transplantation and reducing animal testing in drug development.
Microfluidics: A multidisciplinary field that focuses on manipulating and controlling fluids on a micro-scale, typically within channels smaller than a human hair's width. This technology has wide-ranging applications in chemistry, biology, and engineering, enabling precise and automated handling of tiny volumes of fluids. Microfluidic devices have been used for tasks such as DNA analysis, drug delivery, and point-of-care diagnostics. Their advantages include lower costs, faster results, and reduced waste generation. Microfluidics holds promise for revolutionizing various industries and research areas, offering innovative solutions for fluid-based processes.
Organ-on-a-chip (OOAC): A technology revolutionizes biomedical research by creating micro-scale models of human organs on silicon chips. These microfluidic systems replicate the physiological functions of real organs, enabling scientists to study drug responses, disease mechanisms, and toxicity in a controlled environment. OOACs offer advantages like reduced cost, ethical considerations ( Garcia et al., 2024 ), and quicker results compared to animal testing. Researchers can customize these chips to mimic specific organs and diseases, advancing drug development and personalized medicine. This innovative approach holds promise for accelerating medical breakthroughs and minimizing the need for animal experimentation.