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

diabetic skin model for the first time and demonstrated of patient-derived cell lines can serve as a platform. This
its functionality. However, limitations arise in terms of cell platform has the potential to replace preclinical testing by
maturation owing to challenges in the simultaneous co- implementing a patient-specific microenvironment within
culture of dermal, epidermal, hypodermis, and vascular the created in vitro skin model. 110
cells. Additionally, for a more accurate representation
of diabetes, it is essential for the disease-on-a-chip to 3.2. Blood vessel
be connected to other organ compartments. Despite The vascular system encompasses blood vessels distributed
these limitations, this study serves as a pioneering step throughout the body, typically classified into arteries,
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in the development of skin disease-on-a-chip using 3D veins, and capillaries. Blood vessels play a crucial role
bioprinting. in transporting oxygen, nutrients, and blood to various
tissues while also receiving waste products from these
Although numerous models have been constructed tissues and delivering them to the kidneys. In particular,
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using 3D bioprinting and various hydrogels, such as skin- arteries are characterized by a smooth muscle cell (SMC)
derived dECM, to effectively replicate different aspects layer, providing the strength to withstand high pressure.
of skin in vitro, several areas remain that require further Arteries play a significant role in transporting oxygen-
advancement and practical implementation. Recently, rich blood from the heart to every tissue. Veins, on the
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Ramasamy et al. achieved the rapid fabrication of a full- other hand, are responsible for returning blood from the
thickness skin model structure on a porous PCL scaffold tissues to the heart, featuring valves that prevent backflow.
using 3D bioprinting. The focus of recently developed Meanwhile, capillaries, positioned between arteries and
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3D bioprinting skin models has shifted toward simulating veins, are small blood vessels distributing oxygen-rich
the full-thickness skin structure, incorporating various blood to each individual tissue cell. 114
skin cells, such as melanocytes, to mimic the physiological
characteristics of real skin, and utilizing the skin model as Creating a tubular structure for the flow of liquid is
a disease model. 107 critical in constructing an in vitro blood vessel model.
Moreover, the structure’s capability to withstand hydraulic
However, current 3D bioprinting technology still pressure should be taken into consideration. The integration
relies on limited cell sources and lacks the capacity to co- of vascular structures is essential for the design of organs-
culture multiple cells. Consequently, it falls short of fully on-a-chip. Without the provision of media or oxygen
reproducing unique skin functions owing to limitations through an appropriate vascular structure, significant
in cell maturation, often remaining confined to the issues may arise in the cells constituting the organ-on-a-
simplistic layering of multiple cell layers. Additionally, chip. Therefore, several methods have been developed
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to simulate a microenvironment akin to the skin, the to fabricate vascular structures, with 3D bioprinting
establishment of a highly mature vascular network is emerging as a prominent strategy. These methods include
essential. Unfortunately, this critical issue has not yet the initial printing of a hollow tubular structure followed
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been resolved, underscoring the need for 3D bioprinting by coating the structure with vascular cells or printing a
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technology that can swiftly implement multiple cells and hydrogel containing cells in the form of a ring and stacking
intricate blood vessel networks on a unified platform. A it in multiple layers. Another approach involves coaxial
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recent endeavor attempted to address this challenge by printing of vascular cells with biomaterials capable of
implementing a vascular network via 3D bioprinting using creating sacrificial channels, such as PF-127, followed by
an ultrafast laser. This method stands out as a suitable 3D the removal of the sacrificial material to fabricate hollow
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bioprinting method for producing skin vascular networks, structures. The significance of this research field is
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given its versatility in using various materials and explained through examples of in vitro vascular models
producing structures with curves and various heights. This using 3D bioprinting technology given below.
adaptability makes it well-suited for simulating the complex Anada et al. developed a two-step DLP technology
vascular structures found in the skin. Therefore, the key to based on stereolithography and used it to produce a 3D
success involves securing a skin cell line compatible with bone structure containing numerous blood vessels (Figure
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relevant printing methods and the creation of a single-step 4A). Using the corresponding bioprinting technology,
model within a short period.
a double-ring structure was fabricated with GelMA. The
For skin diseases, an immune system that includes outer ring part simulated the bone, while the inner part
microorganisms is essential. Therefore, there is a need for encapsulated a human umbilical vein endothelial cell
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a model design capable of promptly deploying immune cells (HUVEC) spheroid, mimicking the complex vascular
and microorganisms to the necessary areas. In addition, structure inside the bone. This study holds significance
the study of media that facilitates the stable maturation as it innovatively developed a new bioprinting technique

Volume 10 Issue 1 (2024) 30 https://doi.org/10.36922/ijb.1972