Page 40 - IJB-10-1

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

vascular networks in vitro, several challenges remain that biological homeostasis, regulating factors such as water
require further advancement. Recently, several research content, electrolytes, and acidity. Moreover, the kidney
teams have succeeded in replicating the multilayer structure serves as an endocrine function, producing and activating
of real blood vessels using different hydrogels and cells via various hormones. 124
coaxial printing. As a result, recent 3D bioprinting blood Creating a nephron mimetic is critical for fabricating an
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vessel models are characterized by using advanced printing in vitro kidney model, and it is essential to explore methods
technologies, such as coaxial and in-bath printing, and the that simplify the nephron structure to separately produce
accurate simulation of blood vessel barriers using various endothelial and epithelial cell structures, integrating them
cells, such as endothelial cells and pericytes, to accurately into a unified platform. 65,93,94,125 Additionally, to simulate
mimic physiological properties. In addition, there is a the primary function of the kidney, the filtration function
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focus on processing various inflammation cytokines and and material exchange between the proximal renal
applying them as disease models. 92
tubule and surrounding vasculature must be accurately
However, current 3D bioprinting technology still relies implemented. Renal proximal tubular epithelial cells
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on limited cell sources and cannot connect multiple tubular (RPTECs) and glomerular microvascular endothelial cells
structures to one body within a short period. In addition, (GMECs) are widely used for this purpose. Therefore,
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the existing technology faces limitations in printing from several methods for fabricating in vitro kidney models have
the micrometer to millimeter scale in a single printing been developed, with 3D bioprinting methods emerging as
process, thereby preventing the full implementation of a prominent strategy. In certain methods, a hollow tubular
vascular networks. A promising approach to address structure is initially printed and subsequently coated with
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this challenge is to prepare bioinks containing angiogenic kidney and blood vessel cells. 65,93 Other methods involve
molecules that promote angiogenesis for capillary the simultaneous printing of kidney and blood vessel cells
formation, coupled with appropriate mechanical properties with PF-127, using the coaxial printing method to fabricate
suitable for structure fabrication. This requires in-depth tubular structures with embedded cells. 94,125 Recently, a
studies on mechanobiology, intercellular crosstalk, and novel method has been introduced for preparing an in
the biological response of vascular cells to stimuli such vitro kidney model containing kidney organoids, inducing
as microfluidics and hydraulic pressure. Additionally, the generation of microvessels from the deployed kidney
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advancements in 3D printing technology are essential to organoids. 127,128 Examples of in vitro kidney models using
increase printing speed and enable the instant printing of 3D bioprinting technology are presented below.
vascular structures at precise locations. To achieve this, the
development of multiple nozzle systems of various sizes Lin et al. developed an in vitro kidney model featuring
capable of independently dispensing multiple biomaterials endothelialized and epithelialized dual channels through
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may provide the opportunity to place a variety of materials a 3D extrusion-based bioprinting method. The initial
within one platform at high speeds. step involved filling the kidney-on-a-chip with a gelatin-
fibrin mixed hydrogel (gelbrin ECM), followed by the
Although these studies focus on the creation of printing process through the gelbrin ECM with Pluronic
vascular in vitro models, these techniques enable highly ink. Subsequently, the liquefied Pluronic ink was removed,
customized tissue constructs to be immediately implanted creating a cylindrical channel. RPTECs and GMECs
by integrating clinical images of the patient’s anatomy and were then introduced into each channel to create the
printing the tissue-engineered constructs directly at the cellular luminal structure. The study holds significance
surgical site. Therefore, using this technology, existing as it represents the first in vitro kidney model capable of
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transplantation methods and treatment procedures can simulating the kidney at a significant level, incorporating
be considerably simplified, solving preclinical and clinical endothelialized and epithelialized dual channels while
problems. validating the renal filtration function within the model.
However, it is essential to note that the study has limitations,
3.3. Kidney as it only partially simulated various renal functions and
The kidney is a complex organ consisting of approximately fell short of recapitulating the multicellular layer structure
one million nephrons responsible for the continuous inherent to the kidney.
filtration of blood and excretion of metabolic waste
products. Nephrons themselves comprise approximately Singh et al. advanced the field by developing a kidney-
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20 cell types, including proximal tubule epithelial cells, derived dECM bioink, incorporating RPTECs and GMECs
distal tubule epithelial cells, glomerular podocytes, and to create two distinct in vitro kidney models. Firstly,
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collecting duct cells. In addition to its primary filtering they used a triple-coaxial printing technique to create an
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function, the kidney plays a crucial in maintaining in vitro kidney model featuring a double-shell structure,

Volume 10 Issue 1 (2024) 32 https://doi.org/10.36922/ijb.1972