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

A

B

Figure 7. The blood flow of the regions of interest (ROI) on day 7 (A) and day 14 (B) was evaluated by a laser Doppler perfusion imaging, and ROI value
was plotted on statistical graphs.

Collagen and hyaluronic acid are main components adhesive nature may enable mimicking native skin ECM
in skin ECM. Gelatin (hydrolyzed collagen), with cell microenvironment and were applied to tissue engineering
adhesive functional group in it, is beneficial to adhesion or regenerative medicine [1-7,19-20] , such as skin, cartilage,
and spreading of encapusulated cells; therefore, they could cardiovascular tissue, and disc repair. Therefore, in this
be added to improve the printability of dECM pre-gel. study, 7.5% (w/v) GelMA, 1% (w/v) HAMA, and 1.125%
Hyaluronic acid plays significant role in wound healing, (w/v) dECM were used.
[16]
cell differentiation, and angiogenesis . However, it has
poor mechanical properties. After being modified with The rheological properties of dECM-GelMA-HAMA
methacrylic anhydride, hyaluronic acid can crosslink precursor before photocrosslinking showed that the
to form hydrogel by photocuring. Moreover, due to its temperature to reach G’/G’’ crossover was about 17.5°C. G’
strong moisture retaining ability, HAMA can relieve the is much greater than G’’ when the temperature is lower than
desiccation and contraction of the 3D-bioprinted skin 17.5°C, which means that the crosslink density is high, the
substitute effectively after transplantation. The previous interfacial bond strength is strong, and the precursor exhibits
research indicates that photo-crosslinked GelMA-HAMA the properties of an elastomer. Contrarily, the precursor
hybrid hydrogel provided a suitable microenvironment exhibits the properties of a fluid/sol when the temperature
for hADSCs proliferation, and hADSCs-loaded hydrogels is higher than 17.5°C. We set the temperature of bioink
increased vascularization, which is essential to wound container to higher than 17.5°C so as to avoid clogging of
healing and skin regeneration . It is suggested that the extrusion needle. The SEM imaging showed that the internal
[1]
mechanical properties of scaffold should correspond to structure of photocrosslinked dECM-GelMA-HAMA
the mechanical properties of surrounding tissue. 7.5% composite hydrogel is porous, and the moderate porosity
(w/v) – 10% (w/v) GelMA can maintain physical structure and pore size are suitable for cell migration, proliferation
after printing . To further improve physical properties and tissue engineering applications. The 3D-bioprinted
[17]
and printability, 1% (w/v) HAMA was added to fabricate skin substitute loaded with hADSCs presented regular grid-
composite hydrogel . GelMA-HAMA hybrid hydrogels like structure and uniform pore distribution and size, and
[18]
with excellent mechanical strength, printability, and cell- it was stable without obvious deformation or collapse after

Volume 9 Issue 2 (2023) 403 https://doi.org/10.18063/ijb.v9i2.674