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International Journal of Bioprinting Liver printing: from structure to application

to precisely assemble cells and materials, has become printability of multi-component materials, and is only used
a highly promising approach for liver manufacturing. in theoretical and in vitro research without established
Currently, bioprinted liver tissues have demonstrated application scenarios for 4D bioprinted products, it
a certain level of liver functions, such as the synthesis remains a promising research direction. Robotic arm-
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of ALB and urea, glycogen accumulation, and drug based bioprinting, with its enhanced dimensional freedom,
metabolism. Furthermore, with the introduction of can increase the complexity and flexibility of bioprinting.
cholangiocytes, endothelial cells, and stromal cells, the This technology allows for the printing of various patterns
composition of bioprinted liver tissues is becoming more on curved or dynamic surfaces. Machine learning is
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similar to that of natural liver tissue. Additionally, the also a current research hotspot, as its algorithms can
establishment of perfusable multi-scale vascular networks automatically construct mathematical models and make
has enabled the creation of larger vascularized liver tissues predictions or decisions based on new data. Utilizing
(>1 cm), overcoming the limitations of nutrient and machine learning for the functional evaluation of
oxygen diffusion. bioartificial organs holds promise for optimizing the
Despite the enormous potential of 3D bioprinting cultivation conditions of 3D-printed structures and
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technology, many challenges remain in the field of liver extending the cultivation time. In the future, bioprinting
manufacturing. Firstly, the number and density of cells technology is expected to achieve a significant leap from
currently used to construct liver tissues in vitro remain mimicking the form to replicating the function, thereby
significantly different from those of natural livers, and alleviating the organ shortage crisis and ushering in a new
the size is limited to the centimeter scale, far from the era of regenerative medicine.
size of a natural liver. Secondly, although other cell types
(e.g., cholangiocytes, endothelial cells, and stromal cells) 7. Conclusion
have been incorporated, they often exhibit simple co- This review delves into the field of liver tissue
culture rather than functional interactions. Furthermore, engineering, particularly the cutting-edge applications
the bioinks and subsequent in vitro cultures mainly and potential of 3D bioprinting technology in liver
use natural biomaterials. While these materials may manufacturing. As a crucial internal organ, the liver’s
support cell viability, they often have batch variations, complex structure and diverse functions play a central
and components such as Matrigel and dECM are even role in maintaining vital activities. The article first details
unclear, severely limiting their clinical applications. the physiological functions, cellular composition, and
Hence, developing bioinks with defined components unique development and regeneration mechanisms of the
and adjustable properties is a promising research liver, emphasizing its importance in biomedical research.
direction. Additionally, present bile duct structures can Facing the shortage of liver transplant donors and the
only transport exogenous bile acids, and achieving the limitations of existing alternatives, the article highlights
transport of bile produced by hepatocytes themselves 3D bioprinting technology as an innovative solution
remains challenging. Finally, achieving immunization for liver organ fabrication. This technology, with its
in vitro for the liver, a vital immune organ in the human capabilities for personalized customization, replication
body, has not been successful. of complex structures, and precise arrangement of multi-
Nonetheless, bioprinting technology has made material cells, shows tremendous potential in tissue
significant progress in recent years. Volumetric bioprinting engineering. By reviewing the latest research advances
technology can create entire cell-laden structures of any in liver bioprinting, the article thoroughly introduces the
size and shape within seconds. 184–186 Acoustic-assisted composition and properties of bioinks and their specific
3D printing uses non-contact liquid handling methods applications and outcomes in liver bioprinting. Moreover,
to avoid cross-contamination. This printing method the article deeply analyzes the current challenges in liver
also overcomes nozzle limitations, avoiding issues such fabrication, such as constructing vascular and bile duct
as nozzle-clogging. Additionally, ultrasonic standing structures, and explores future development directions. It
waves and acoustics-based bioprinting can be applied to emphasizes the critical role of ongoing efforts to optimize
microfluidic technology, enabling the manipulation of biomaterials, cell sources, and printing technologies in
particles and cells. 187–195 4D bioprinting technology is also advancing liver biofabrication toward clinical application.
gradually emerging. By combining the fourth dimension In summary, this article aims to provide a comprehensive
“time” with 3D printing, it is possible to simulate the and in-depth perspective for researchers in the field of
complex dynamics of natural tissues, thereby improving liver tissue engineering, and to offer insights into future
the functional response of constructed tissues. Although directions for innovation and development in liver
current 4D bioprinting lacks biocompatibility and the disease treatment strategies.

Volume 10 Issue 5 (2024) 142 doi: 10.36922/ijb.3819