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International Journal of Bioprinting 3D-printed skin substitute accelerates wound healing in vivo

several hours incubated in medium. The pores in it could GelMA-HAMA skin substitute loaded with hADSCs
increase surface area, facilitating drainage of exudate and positively influences multiple phases in wound healing
exchange of gases and nutrients. process, including re-epithelialization, dermal collagen
In terms of the selection of seed cells, although deposition and arrangement, attenuation of inflammatory
keratinocytes and fibroblasts are mostly used as seed cells in response, promotion of angiogenesis, and increase in blood
skin tissue engineering studies, the transformation of both perfusion, to ultimately play a positive role in accelerating
cells in clinical application is subject to various restrictions. wound healing and improving the quality of wound healing.
The harvest of keratinocytes from patients, proliferation This skin substitute is a possible alternative for repairing
in vitro and application to patients the preparation process skin defect when donor sources are scarce.
of Epicel , take several weeks to complete, and it is too This article mainly focuses on the in vivo application
TM
expensive for ordinary people. The other tissue-engineered of this skin substitute, and its role in promoting wound
®
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skin products, such as Dermagraft and Apligraf , including healing was confirmed by animal experiments. On day 7,
allogenic fibroblast, will also be rejected by patients. A large the skin substitute is still preserved on the wound, but
amount of autologous or allogenic skin tissue is needed the volume has become smaller due to degradation and
to obtain enough cells for tissue construction but massive drying of material. Biological scaffold was used to provide
acquisition of tissue from the donors would cause tissue a microenvironment for encapsulated cells and in situ
defects and dysfunction, which is against the original cells. The scaffold was gradually degraded and absorbed,
intention of tissue engineering and regenerative medicine. and the newly generated ECM finally replaces scaffold,
Moreover, the long cell expansion time prolongs the realizing regeneration and achieving wound healing .
[2]
patients’ pain and increases the chances of acute wounds Therefore, how to match the degradation and absorption
becoming chronic wounds. Several advantages of ADSCs rate of material with the formation rate of tissue, prolong
are as follows: (i) The method to obtain adipose tissue is the survival of encapsulated stem cells and increase cell
easy and less invasive; (ii) the proliferation rate of ADSCs is viability to further make a difference on wound are still
higher under the same culture conditions among many adult problems that need to be further studied. The composite
stem cells; (iii) in the disease microenvironment, ADSCs scaffold prepared in this study is gelatinous. Although
can maintain the cellular state better and play a significant the 3D structure is stable, its mechanical strength is far
role in regulating the microenvironment ; (iv) the human from meeting the requirements of clinical transformation
[21]
leukocyte antigen-A, B, and C expression in ADSCs is of skin. Synthetic biomaterials, such as polycaprolactone
lesser so that little immunoreactivity is induced even after and polylactic acid, could be considered to increase the
allogeneic mesenchymal stem cells transplantation ; and mechanical properties of scaffold [26,27] . On the basis of
[22]
(v) ADSCs can secrete a variety of cytokines by paracrine this study, the material and ratio of bioink can be further
mechanisms, which play a significant role in wound developed to improve the biomechanical properties and
healing . Cell viability of hADSCs is not significantly accurately reproduce the composition of native skin
[23]
affected by shear force, temperature and photo-crosslinking ECM. 3D bioprinting is used to emulate skin geometry.
during the printing process, showing that it is suitable for Although there are many advantages in simulating
3D bioprinting. Nonetheless, it is still necessary to pay the structure of skin, it is still challenging to print the
attention to the impact of the printing process on the ability pigmented tissue-engineered skin with developed blood
of cells to survive, proliferate, and differentiate . vessel, hair follicle, sweat gland, and nerve. In addition, the
[4]
In this study, mice in Group A were treated with damages that could influence cell survival, proliferation
autologous skin graft, which is the “gold standard” option and differentiation during the printing process should
for repairing wounds. Mice in Group B were experimental not be neglected. In future research, we will continue to
group and were treated with skin substitute loaded with evaluate the phenotype, migration, survival and viability
hADSCs. In Group C, a full-thickness skin specimen was of cells, and material absorption and degradation rates in
finely cut with scissors and placed on the wound evenly, with the scaffolds in relation to new skin tissue formation to
a small part of wound exposed, to simulate the skin defect better understand the interaction between ADSCs and
larger than the skin sample [24,25] . No additional treatment dECM-GelMA-HAMA composite hydrogels, and further
was applied to mice in Group D, which was considered solve the problem of matching tissue formation rate with
the control group. By comparing different treatment the material absorption and degradation rates.
methods in clinical practice, the therapeutic effect of skin 5. Conclusion
substitute on wounds was investigated. Wound healing
process consists of four phases: hemostasis, inflammation, dECM-GelMA-HAMA precursor with a sol-gel phase
proliferation, and remodeling. 3D-bioprinted dECM- transition and porous structure can be used as a

Volume 9 Issue 2 (2023) 404 https://doi.org/10.18063/ijb.v9i2.674