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Vascularization of printed bilayer skin grafts
skin grafts on full-thickness wounds in nude direct writing (DW) technology and implanted
mice improved the degree of wound shrinkage. for the repair of damaged skin on the back of
Wound contraction in the cell groups (printed skin mice in this study. The DW cell-printing process
transplantation group and non-endothelial control developed by our lab achieved more than a 90%
group) improved to varying degrees compared with cell survival rate for all three skin-specific cell
the other two groups (cell-free control and blank types and facilitated the manufacture of a bilayer
control groups). However, we did not observe a structure which integrated with host tissue within
decrease in wound contraction over time, due to a wound. Animal experimental results indicate
tissue remodeling into normal tissue. The possible that the composite constructs with or without
reason is that the post-operative observation time cells can assist skin wound healing, but constructs
was not long enough, but we believe that printing with cells had the clear advantage of microvessels
double-layer skin grafts would effectively improve regeneration. Four weeks after surgery, the
wound contraction in long-term applications. constructs containing cells had an approximately
Histological observations showed that the skin 10% increase in wound contraction compared
grafts formed epidermal and dermal layers 14 days to the other groups, promoting microvessels and
after surgery, and microvessels are formed, mainly skin tissue regeneration, as demonstrated by
due to the microvascular endothelial cells within histological and immunohistochemical analysis.
the printed skin grafts. In addition, due to the in vivo
environment providing appropriate stimulation, Acknowledgments
unlike the in vitro environment, such as the presence This work was supported by grants from the
of relevant growth factors, the printed cells in Science and Technology Projects of PLA
the skin graft underwent functional phenotypic (BWS17J036, 18-163-13-ZT-003-011-01) and the
remodeling. We can be certain that the printed National Natural Science Foundation of China
microvascular endothelial cells were involved in (51835010 and 51375371). We thank Health
the formation of the microvessels during tissue Science Center of Xi’an Jiaotong University for
regeneration, but mouse cells may also participate animal experiments, as well as Mr Linian Zhou for
in the repair process through migration or other his hard work of printing experiments and Mz Lin
mechanisms. The majority of other studies have Gao of histology analysis.
used collagen or other materials as extracellular
matrix . Sodium alginate and gelatin were used in References
[35]
the present study. The good healing response of the
animal model and results of histology establish that 1. Rognoni E, Walko G, 2019, The Roles of YAP/TAZ and
the use of this hybrid material can achieve excellent the Hippo Pathway in Healthy and Diseased Skin. Cells,
results, forming tissue similar to physiological 8(5):E411. DOI: 10.3390/cells8050411.
tissue. Microvessel is one of the most important 2. Prost-Squarcioni C, 2006, Histology of Skin and Hair
skin appendages . No other appendages such as Follicle. Med Sci (Paris), 22(2):131–7. DOI: 10.1051/
[36]
hair follicles , sweat glands, or nerves were medsci/2006222131.
[37]
[38]
observed in this study. We speculate that generation 3. Bernerd F, 2005, Human Skin Reconstructed in vitro as a
of these appendages may require inclusion of Model to Study the Keratinocyte, the Fibroblast and Their
additional components or cells in the printed skin Interactions: Photodamage and Repair Processes. J Soc Biol,
graft. A design that is more rational and closer to the 199(4):313–20.
physiological tissue is also required. 4. Kim SW, Choi SH, Kim JT, et al., 2015, An Additional
Option for Split-Thickness Skin Graft Donors: The Previous
5 Conclusions Free Flap Sites. Ann Plast Surg, 75(6):634–6. DOI: 10.1097/
SAP.0000000000000143.
A gelatin-alginate composite mixed with three 5. Wei LG, Chang HI, Wang Y, et al., 2019, A Gelatin/Collagen/
skin-specific cell types was manufactured using Polycaprolactone Scaffold for Skin Regeneration. PeerJ,

62 International Journal of Bioprinting (2020)–Volume 6, Issue 1