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International Journal of Bioprinting Bioprinted organ-on-a-chip with biomaterials

1. Introduction on-a-chip, involving the loading of organoids onto
microfluidic platforms. An organ-on-a-dish represents
Research into new drug development and disease another 3D in vitro model, involving the removal of
mechanisms is currently underway, driven by the human tissue for cultivation in a dish. This model
growing interest in health and the advancements in the facilitates straightforward observation of physiological
pharmaceutical and biomedical engineering fields. These phenomena by utilizing actual tissues, including all cells
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studies require a suitable test model for drug validation or and the extracellular matrix (ECM) that constitute organs.
mechanistic confirmation. Animal testing, a conventional However, an organ-on-a-dish presents challenges in terms
approach, relies on predicting clinical outcomes based of control owing to the accumulation of cellular waste
on observed similarities with clinical trials. However, products, low repeatability, and the occurrence of hypoxia,
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the drawbacks of animal testing are notable, including resulting in frequent partial necrosis. 11,13 Conversely, an
its high cost and the inability to comprehensively reflect organ-on-a-chip is a device wherein cells are encapsulated
human pathophysiology owing to the genetic variations in a microfluidic platform featuring precisely fabricated
across species. Additionally, ethical considerations tied chambers and channels. This model has gained substantial
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to respect for life underscore the need for a thoughtful attention for its ability to replicate organ-level functions.
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examination of the current practices. Therefore, an Notwithstanding its relative simplicity compared to native
imperative has emerged for the identification and tissues and organs, an organ-on-a-chip effectively mimics
implementation of substitutes for animal models in the human physiology and disease. Its ease of manipulation
realm of pharmaceutical and biomedical studies. contributes to high accuracy as a drug testing platform. 14
To overcome these limitations, a range of in vitro models Several factors must be considered in fabricating a
has emerged, leveraging the synergies of biotechnology precise organ-on-a-chip, including biomaterials, cell
and microtechnology to emulate key aspects of human types, humanized designs, and biofabrication methods 15,16
physiology. A notable advancement in this domain is (Figure 1B). The selection of appropriate biomaterials is
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the establishment of a human cell-based in vitro model essential because these biomaterials possess varied physical
designed to faithfully recapitulate the microenvironment properties based on their molecular structure, providing
of human organs. The significance of tissue- or organ- the ECM necessary for structural support in an organ-on-
specific microenvironments cannot be overstated, as they a-chip. Additionally, organ-targeted cells and simplified
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profoundly influence cell–cell interactions and maturation human-like structural characteristics must be considered
processes. The utility of these in vitro models extends across to accurately reflect the structural specificity and function
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diverse fields, finding applications in critical areas such as of organs on an organ-on-a-chip. 16
drug-screening and pathology research. A fundamental Traditional manufacturing methods, such as
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categorization of in vitro models delineates them into photopatterning, lithography, soft lithography, and self-
two-dimensional (2D) and three-dimensional (3D) assembly, have been used for several years to fabricate
models. While the 2D models offer ease of manipulation microfluidic devices and organ-on-a-chip platforms.
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and facilitate high-throughput drug screening, their However, these traditional methods are time-consuming
limitations become evident in the inability to concurrently and expensive owing to their complexity, manual
support the growth of multiple cell types and accurately procedures, and challenges associated with introducing
replicate specific physiological phenomena such as 3D new designs or modifications. Material diversity may
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arrangements and cell–cell crosstalk. In response to these also be limited, and compatibility issues with cells may
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limitations, 3D in vitro models have been developed to arise, especially when specific materials like silicon wafers
provide an environment that closely mirrors the physical are used. 19
and biochemical conditions within the actual human body.
The recent development of 3D bioprinting technology
Representative 3D in vitro models include organoids, has led to a shift away from traditional manufacturing
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organs-on-a-chip, and organs-on-a-dish (Figure 1A). methods for producing organ-on-a-chip. When utilizing
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Organoids are 3D cell clusters wherein stem cells 3D printing, multiple cells can be encapsulated on the
self-organize under specific conditions, comprising platform in a single step and within a short period,
multiple organ-specific cell types and effectively achieving precise 3D biomimetics that enable preclinical
reflecting physiological characteristics. Genetically analysis with a higher degree of predictive power. In
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manipulatable and well-suited for organ development, comparison to traditional manufacturing technologies, 3D
organoids face challenges in implementing organ-specific bioprinting offers advantages such as an unlimited design
microenvironments, such as fluid flow. 10,12 Therefore, recent scope, freedom to make design changes, the capability to
research on organoids has primarily employed organoids- produce complex geometries, and reduced waste. This

Volume 10 Issue 1 (2024) 21 https://doi.org/10.36922/ijb.1972