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

the construction of physiological and anatomical tissues of biocompatible polymers or hydrogels. Hydrogels,
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through the precise patterning and stacking of diverse constituting a 3D network structure comprised of
cells and biomaterials. Additionally, it enables the moisture-absorbing polymers, possess unique properties.
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fabrication of complex microfluidic channels that mimic The polymer chains have the ability to absorb and retain
vascular networks on the organ-on-a-chip in a single moisture, establishing a high-moisture environment.
step. Blood vessels are essential for precisely simulating Leveraging these properties, hydrogels are commonly used
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organs, as all organs inherently comprise a plurality as a form of bioink for 3D bioprinting of living cells, proving
of blood vessels. In particular, a structure combining suitable for fabricating various shapes. These hydrogels
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several tissues, such as the sinusoidal structure of the consist of peptide chains or polymers that are initially
liver, can be implemented within an organ-on-a-chip. printed in a liquid form and subsequently crosslinked to
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This capability enables the accurate mimicking of cell–cell form macromolecular networks in a solid form. 30
interactions and cell–cell signaling, thereby aiding in the
study of disease mechanisms and drug screening. Owing Hydrogels encompass both natural and synthetic
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to these technical advantages, 3D-bioprinted organ-on- biomaterials. Certain hydrogels are derived from natural
a-chip platforms are widely used as precise drug testing biomaterials; for example, collagen-derived hydrogels are
platforms and can be seamlessly integrated with devices often based on collagen extracted from animal skin or
such as bioreactors. Additionally, organ-on-a-chip cartilage. Additionally, alginate-derived hydrogels can be
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finds applications in disease-on-a-chip by adapting a fabricated using ingredients sourced from seaweed. These
pathophysiological microenvironment to elucidate disease natural hydrogels exhibit high biocompatibility and are
mechanisms. In particular, it holds the potential for well-suited for simulating the tissue microenvironment in
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personalized treatment by bioprinting a specific patient’s an organ-on-a-chip. In contrast, synthetic hydrogels are
cells or tissue structure. 20 crafted from synthetic materials. Comprising polymers
or monomers, synthetic hydrogels can possess controlled
This review summarizes the feasibility of using 3D physical properties and can be designed to suit different
bioprinting for the fabrication of organ-on-a-chip. The applications. 32
subsequent sections are structured as follows: Section
2 introduces the latest 3D bioprinting technologies As such, biomaterials used in 3D bioprinting are
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employed in organ-on-a-chip fabrication, with a focus on broadly classified into natural and synthetic materials.
biomaterials such as hydrogels used as bioinks; Section The subsequent sections discuss the biomaterials
3 presents examples of 3D-bioprinted organ-on-a-chip, extensively used in 3D bioprinting for the fabrication of
reflecting their ability to replicate the physiological organ-on-a-chip. A summary of the characteristics of these
functions of various organs; and Section 4 discusses the biomaterials is provided in Table 1.
current limitations of 3D printing technologies for organ- 2.1.1. Natural biomaterials
on-a-chip fabrication, along with issues related to organ- Natural biomaterials, such as collagen, gelatin, alginate,
on-a-chip. Moreover, this review discusses methods to silk fibroin (SF), and decellularized ECM (dECM), are
overcome these limitations and presents strategies for the extracted from various organisms and possess high
development of 3D-bioprinted organ-on-a-chip.
biocompatibility. These natural biomaterials find extensive
2. Latest 3D bioprinting techniques for use as cell-encapsulating bioinks in 3D bioprinting for the
fabrication of organ-on-a-chip, owing to their ability to
organ-on-a-chip fabrication sufficiently protect encapsulated cells. This protection is
2.1. Materials for 3D bioprinting attributed to their high water content and viscoelasticity,
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The selection of biomaterials used as bioink is critical in the ensuring the protection of cells from external hazards such
fabrication of organ-on-a-chip through 3D bioprinting. as contaminants in the printing space or mechanical stress
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These biomaterials are crucial as they provide the necessary during passage through the printing nozzle. Examples
microenvironment for cells and contribute to structural of these natural biomaterials and their properties are
support. Several key parameters merit consideration discussed below.
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when choosing biomaterials for bioprinting, including Collagen, a primary component of various organs,
biocompatibility, printability, stiffness, and crosslinking stands out for its exceptional biocompatibility and
methods. 28
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numerous binding sites that facilitate cell adhesion.
Biomaterials serve as diverse forms of bioink, a Additionally, collagen exhibits thermal gelation properties,
specialized ink used in 3D bioprinting to create 3D biodegradability, and a low inflammatory response.
biological models. Bioink is mainly produced in the form Among various collagen subtypes, collagen type 1 is the

Volume 10 Issue 1 (2024) 23 https://doi.org/10.36922/ijb.1972