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International Journal of Bioprinting 3D bioprinting for vascularized skin tissue engineering

As shown in Figure 9B, HDMECs migrated out of the effort is needed to fabricate therapeutically useful vascular
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Matrigel by day 7, forming networked tube-like formations structures. Increasing the complexity of the constructed
adjacent to the PHBV channel borders. More effective tube- objects and improving the physical composition of
like structures were formed through the addition of VEGF- biomaterials relevant to different cell types are necessary.
loaded Matrigel; this effect was significantly identified Bioprinting holds tremendous promise for
when the proangiogenic compounds 2dDR and VEGF revolutionizing vascularization in tissue engineering. This
were added. About 20% of the Matrigel tested with VEGF advanced technology has the potential to significantly
loading and 13.3% of the Matrigel tested with 2dDR loading enhance the creation of functional blood vessels in
in the control group showed structures mimicking tubes. As engineered tissues, addressing critical challenges in
shown in Figure 9C, PHBV scaffolds with HDMECs and regenerative medicine. Manufacturing processes in
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HDFs showed uniformly distributed channels with HDFs bioprinting enable precise control over the architecture
on the outside of the structure. High-magnification images of vascular networks. Bioprinters can deposit bioinks
of the reconstituted skin models, primarily constructed composed of living cells, growth factors, and biomaterials
from electrospun sheets, showed that CD31-positive in intricate patterns that mimic natural blood vessel
HDMECs were proliferating within the PHBV channels. An structures. This level of control allows for the customization
in vivo study showed that the dry eye disease (DED) group of vessel size, shape, and branching, catering to the specific
had the fewest blood vessels, while tissue-engineered skin needs of different tissues. One key advantage of bioprinting
analogs with 2dDR had the most significant vascularization. is its ability to support the maturation of engineered blood
Figure 9D shows that the function of proangiogenic vessels. Over time, printed vessels can develop into more
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chemicals and dermal cells markedly enhanced the vascular functional and stable networks. As cells populate the
count. The PHBV SVN can be a useful platform for in vitro bioink and self-organize, they can remodel the vascular
angiogenesis research for evaluating vascularization in structures that bear high resemblance to native vessels.
human skin development, as this study demonstrates. This maturation potential is crucial for long-term tissue
viability. Moreover, bioprinting is making strides in
6. Conclusion and future perspectives the development of functional trilayer blood vessels. In
addition to the inner endothelial layer that interfaces
Multiple approaches can be used in skin tissue engineering with blood, bioprinters can deposit smooth muscle cells
to facilitate the biofabrication of vascular structures.
The integration of specific cell types, application of for the middle layer and fibroblasts for the outer layer.
growth factors, and use of biomaterials can promote the This trilayer configuration closely mimics natural blood
development of new blood vessels. In contrast to other vessels, contributing to better blood flow regulation and
tissue integration. In the future, bioprinting may facilitate
organs where vascularization can occur from adjacent the creation of highly vascularized tissues and organs for
surfaces, proper vascularization from beneath is crucial transplantation, wound healing, and disease modeling.
for the absorption of any tissue construct in the skin. By harnessing the power of precise manufacturing,
Achieving proper vascularization is challenging because maturation potential, and trilayer vessel development,
all cells within the biofabricated construct typically require bioprinting promises to significantly advance the field
higher metabolic activity during the first transplantation of vascularization and improve the success of tissue-
phase. The physiological limitations of vascularization engineered products in clinical applications.
in normal skin represent the largest barrier to vascular
neoformation, and they become less severe over time. Acknowledgments
Long-term preclinical investigations are necessary to
assess the vascularization rate. Currently, a perfused The schematics of Figures 1 and 5 were created by
construct developed using in vitro techniques must the authors using images provided by BioRender
successfully integrate blood vessels within the construct (https://biorender.com/).
to achieve complete vascularization under both in vitro
and in vivo conditions. Further research is needed to Funding
achieve equilibrium in the implementation of large-scale This work was supported by Pusan National University
regenerative skin treatment options. Despite extensive Research Grant, 2021 and by National Research Foundation
research, challenges remain in the field of tissue vascular of Korea (NRF) grants funded by the Korean government
engineering. Although significant advancements have (MSIT) (No. 2022R1A5A2027161, 2022R1C1C1004803,
been made in 3D bioprinting since the development of the and RS-2023-00214149) and by the Institute of Civil-Military
first tissue-engineered blood vessel over 50 years ago, more Technology Cooperation funded by the Defense Acquisition

Volume 10 Issue 3 (2024) 106 doi: 10.36922/ijb.1727