Page 444 - IJB-9-3

International Journal of Bioprinting Gelatin-PVA crosslinked genipin bioinks for skin tissue engineering

provides a desirable property to enhance cellular activities crosslinked with 0.1% of GNP, the degree of crosslinking
and influence the moisture of the printed hydrogels. findings revealed that the hydrogels had a crosslinking
A moist environment promotes wound healing by level of >40%. Arif et al., who studied the effects of 0.1%
enabling the encapsulated cells to migrate freely through GNP crosslinking on the gelatin hydrogel, also found that
the hydrogels that are often present in wound exudate . the hydrogels have roughly a crosslinking degree of 39% .
[56]
[47]
Moreover, the previous studies by Zidaric et al. suggested It was found that without crosslinking, gelatin hydrogels
that the hydrophilicity and viscosity of the bioinks solution will have poor shape stability and mechanical strength,
have a significant impact on the printing accuracy and live thereby limiting their biomedical applications .
[57]
[47]
cell encapsulation . Consequently, hydrophobic bioinks Moreover, genipin is preferable over other crosslinkers
[48]
prevent the bioinks from spreading well during printing . not only because it functions as a crosslinker, but also
Next, an ideal skin substitute is characterized by an because of its biological activities, including anti-
optimum water uptake capacity through swelling ratio. inflammatory and antioxidant properties that are produced
A study by Agubata et al. suggested that a hydrogel candidate by the GNP . Continuous inflammation, pathogen
[58]
for wound healing applications should have a water holding infection, and oxidative stress are a few variables that might
capacity of about 500%, as this will prevent exudates from adversely influence the healing process of wounds. The
accumulating in the wound area . This finding was similar antioxidant properties of the hydrogels were determined
[49]
with our swelling ratio results that were considered fit for by measuring the free radical scavenging activity through
wound healing application as it has >500% of swelling ratio. DPPH and ABTS assay. After crosslinked with GNP, the
However, the swelling ratio decreased in the presence of hydrogels have been shown to have a scavenging activity
PVA in the hydrogels. This finding was comparable with of >25%, as shown in Figure 3F and G. Since 0.1% of GNP
a previous study on the gelatin-PVA hydrogels by Jeong et was employed in this research, it might have antioxidant
al., which indicated that the swelling ratio decreased when effects that maintain cell proliferation activity. Notably, a
[50]
the concentration of PVA increased . This phenomenon significant finding by Kim et al. found that higher dosages
occurred due to the formation of covalent bonds between of GNP would increase the quantity of reactive oxygen
the functional groups of the gelatin and PVA, which might species (ROS) and induce cytotoxicity, whereas only low
cause smaller pore sizes . In addition, an ideal WVTR doses of GNP will have antioxidant properties . Moreover,
[50]
[59]
might keep skin at the proper degree of moisture and could Fan et al. found that GNP seems to activate numerous key
prevent dryness or maceration from damaging a wound by genes encoding antioxidant and xenobiotic-metabolizing
regulating the moisture of the microenvironment . In this enzymes . Due to its antioxidant characteristics, genipin
[51]
[60]
study, the crosslinked hydrogels have WVTR in the range has been explored as a possible cancer treatment . On
[61]
of 700–1200 g/m /h, which was ideal for rapid wound the other hand, a comparison research carried out by
2
recovery. This finding is similar with the previous studies Zulkiflee & Fauzi found that gelatin and PVA polymers do
by Sutar et al. and Lou, which indicated the normal WVTR not have any antioxidant characteristics, unless additional
2
for normal skin was 204 g/m /24 h while for injured skin antioxidant components are included .
[14]
2
was 279 g/m /24 h [52,53] . Moreover, the literature also claims
that human skin transpires water vapor at a rate of between 4.3. Hybrid bioinks printability through extrusion-
240 and 1920 g/m every 24 h . based bioprinting
[54]
2
Viscosity of bioinks is crucial for extrusion-based
4.2. Dual-functions of genipin on hybrid bioinks bioprinting. Moreover, the hydrogels’ shear-thinning
development properties rely on the viscosity of the bioinks . Higher
[16]
Besides, degree of crosslinking was another criterion viscosity of bioinks will clog the dispensing nozzle
considered for skin application. Crosslinking of the during extrusion, while lower viscosity of bioinks will
hydrogel has been shown to be an effective method for cause extruded filaments to overspread and collapse .
[62]
enhancing both the mechanical and thermal properties of According to our finding, the viscosity of gelatin bioinks
the hydrogels. As the gels successfully crosslinked with the increased with the addition of PVA and crosslinker.
genipin (GNP), the hydrogels turned blue. This is because A previous study by Tung et al. suggested that the viscosity
the hydrogel network contains amino groups, causing GNP remained more stable with higher PVA content, preserving
to interact with the hydrogels. As a result, this phenomenon the usual pseudoplastic behavior of hydrogels [63], and Masri
occurs. Moreover, the results of this investigation are et al. reported the similar finding in which the viscosity of
consistent with other study by Butler et al., which indicated the gelatin hydrogel increased with the addition of genipin
that the polymerization of genipin by oxygen radicals and PVA . On the other hand, the storage modulus (G’)
[64]
results in the formation of a blue pigment . After being of hydrogels with varying viscosities was measured to
[55]
Volume 9 Issue 3 (2023) 436 https://doi.org/10.18063/ijb.677