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International Journal of Bioprinting dECM bioink for in vitro disease modeling

models has ushered in the advent of three-dimensional recapitulate whole proteins in the native tissues with
(3D) in vitro models, which enable 3D cell–cell, cell–tissue, chemically designed hydrogels. In particular, each tissue
and tissue–tissue interactions. The 3D in vitro model has a specific protein composition and specific mechanical
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has attained a swift advancement under the expectation properties; thus, full reproduction of the ECM composition
that the system can imitate complex physiology via the with synthetic materials is difficult. From this viewpoint,
recapitulation of interactions in the body not found in the decellularized extracellular matrix (dECM)-based
animal models or non-physiological models. In particular, hydrogel is a favorable material to satisfy the requirements
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in vitro disease models that recapitulate specific features of tissue recapitulation. 13,14 Fabrication of a dECM
of patients are widely adopted in the study of disease essentially involves the reduction of cellular components
mechanisms and pharmaceutical development. A precisely and preservation of proteins—particularly the ECM; thus,
designed 3D in vitro model should contain cells and it is advantageous for maintaining tissue specificity.
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extracellular matrix (ECM) in the right composition, as Through the use of tissue-specific decellularization
well as microstructure of the tissues or organs. Therefore, methods, various dECMs have been developed from
applying an appropriate biofabrication strategy together organs such as the brain, cornea, bone, skin, and liver. The
with a combination of biomaterials can help establish in developed dECMs exhibit tissue-specific biochemical and
vitro models with proper physiological reliability. mechanical properties. For example, Han et al. investigated
Biomaterials are used in in vitro models as essential the direct differentiation potential of adult stem cells in a
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scaffolds for tissue analogs. Various biomaterials, including dECM bioink. Because of their multipotency, the adult
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nature-derived ECM and synthetic materials, have been stem cells differentiated into the targeted tissues, including
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employed to build in vitro models over the past decades. those of liver, skin, cornea, and heart, depending on the
These biomaterials are closely related to the regulation bioinks used. The Matrisome and ATLAS databases
of cellular behavior. In particular, the interaction of indicate tissue-specific functions of ECMs with regard
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nature-derived ECMs with cells has been elucidated and to organ homeostasis and maturation, respectively. 17,18
compared with synthetic biomaterials. Since, however, Collectively, the role of ECMs in simulating tissue function
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the conventional natural biomaterials, such as collagens, has been profoundly elucidated using dECMs.
laminins, and fibronectins, are chemically less complex In terms of biofabrication, 3D bioprinting is useful for
than ECM of native tissues, it is rather challenging fabricating various structures with a high manufacturing
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to investigate their exact cellular behavior related to degree of freedom. 3D bioprinting is a layer-by-layer
tissue specificity. Thus, it is necessary to develop more fabrication method for obtaining tissue analogs via
native tissue-like biomaterials for enhancing cell–ECM
interactions in in vitro models. additive manufacturing, by employing biomaterials, cells,
and other biological components, such as growth factors.
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Additionally, biofabrication methods (e.g., The notable advantage of 3D bioprinting, compared to
photolithography, bioprinting, organoid formation) have traditional photolithography or organoid formation, is
been used in attempts to reconstruct the 3D physiological its enhanced prowess in recapitulating 3D physiological
structure of native tissues. The physiological structure structures. Various 3D bioprinting methods, such as
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of each tissue is closely related to the essential role of the extrusion-based, inkjet-based, and laser-assisted, can be
organ. For example, a tubular-like and perfusable structure selected by users in considerations with the materials,
is the key feature of vascular tissues. In addition, epithelial precision level, and designed structure. 21-24 Extrusion-
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tissues have layered structures composed of several cell based bioprinting employs pneumatic or mechanical
sheets, and muscular tissues have bundle structures pressure with shear-thinning biomaterials such as
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that can contract and expand. Thus, recapitulation hydrogels or thermoplastics. 22,25 It is compatible with a
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of innate features of tissues is essential for elucidating wide range of printing materials, as most shear-thinning
the tissue–tissue interactions in organisms. However, materials, including cell-laden hydrogels, can be adopted.
photolithography-based models are simplified into almost In addition, extrusion-based bioprinting yields low
two-dimensional (2D) structures, and traditional organoid thermal stress during the fabrication process, which is
generation is restricted owing to the lack of spatiotemporal favorable for high cellular viability. However, shear stress
regulation of cells and ECM placement in the context of due to highly viscous material and nozzle clogging due to
bioengineered design. cell clusters can damage cells. Inkjet-based bioprinting

Therefore, native tissue-derived biomaterials and employs electrohydrodynamic drop-on-demand
spatial-controllable biofabrication methods have been control. 23,26 It is advantageous in terms of fabrication
suggested to improve the level of tissue recapitulation. speed, but it has limited control precision owing to non-
First, for the biomaterials, it is technically difficult to uniform droplet formation. On the other hand, laser-

Volume 10 Issue 2 (2024) 132 doi: 10.36922/ijb.1970