Page 446 - IJB-9-3

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

toward HDFs. This discovery is confirmed by Barba et al. properties based on their swelling characteristics. The
and Masri et al., who discovered that both gelatin and PVA composite bioinks demonstrated excellent fluid absorption
are biocompatible to HDFs, with cell viability of >88%, capacity with hydrophilic properties. The addition of PVA
evaluated on gelatin and PVA hydrogels [64,74] . Furthermore, developed biostable rheological properties for the bioinks
the live/dead assay that measures the cell proliferation without impairing the printability and in vitro testing
activity revealed that the gelatin-PVA bioinks were able towards HDFs. The in vitro cytotoxicity testing through live/
to support HDFs proliferation and offered a conducive dead staining showed that the addition of PVA resulted in
environment for cell growth. Besides, an in vitro wound excellent cell viability after bioprinting. The GPVA bioinks
scratch assay was performed to evaluate the migration thus demonstrated outstanding physicochemical and
activity of the HDFs for future wound healing application. rheological qualities and satisfied all criteria for suitable
The results in Figure 7E demonstrated that both gelatin medical applications. As a result, it has good physical and
and gelatin-PVA hydrogels indicated an efficient cell forming qualities, making it as a potential cellular skin
migration activity after 72-h exposure to the hydrogel’s replacement.
leachate media. The cell monolayer scratch was partially
closed after 24 h and fully closed after 72 h of leachate Acknowledgments
treatments as compared to the controls. A similar finding
was observed in a previous study by George et al., which All authors would like to express immense gratitude
indicated that the cell monolayers moved toward the to the Faculty of Medicine, UKM for the guidance and
opening of the scratch region and partially closed after resources to complete this manuscript. This study has
[75]
treatment with biomaterial leachate for 24 h . been performed under good quality management of ISO
9001:2015 for research facilities.
Gelatin-PVA scaffolds with particular ratios can
mimic natural tissues for cell adhesion and growth. Funding
However, a study by Kakarla et al. found that the higher
PVA concentrations in the hydrogel may reduce HDFs The study was funded by Ministry of Higher Education
growth . Besides, due to PVA’s lack of cell adhesion (MoHE) under the Skim Geran Penyelidikan Fundamental
[76]
sites, larger amounts may limit cell attachment. This (FRGS), grant code: FRGS/1/2020/STG05/UKM/02/7.
finding can be confirmed by a previous study on pure Conflict of interest
PVA by Jeong et al., which found no cell adhesion activity
due to the absence of ligands bound to cell-surface The authors declare no conflict of interest.
receptors . However, there was no distinct difference on
[50]
cell attachment activity between gelatin and gelatin-PVA Author contributions
hydrogels. In addition, the morphological structure of cells Conceptualization: Syafira Masri, Ruszymah Idrus, Mh
was observed using SEM after encapsulated in the bioinks. Busra Fauzi
Figure 7D demonstrates that the HDFs emerged as small Investigation: Syafira Masri, Izhar Abd Aziz, Mh Busra
spherical forms and were evenly distributed on the surface Fauzi
of the gelatin-PVA hydrogels. Moreover, Thangprasert Methodology: Syafira Masri, Manira Maarof, Mh Busra
et al. and Yannas et al. reported similar results for the Fauzi
morphological structure of encapsulated cells in bioinks Formal analysis: Syafira Masri
with spherical-shaped cells and maintained cell viability Writing – original draft: Syafira Masri
in different types of hydrogels after days 5 and 7 [70,71] . Writing – review & editing: Syafira Masri, Manira Maarof,
According to the findings by Crosby et al., HDFs have an
expanded morphology in softer hydrogels and appear as Ruszymah Idrus, Mh Busra Fauzi.
rounded/spherical shapes in stiffer hydrogels . Ethics approval and consent to participate
[77]
5. Conclusion The study design was approved by the Universiti
GPVA bioinks were successfully fabricated using Kebangsaan Malaysia Research Ethics Committee (Code
extrusion-based bioprinting with promising printability at no. FF-2021-376 and JEP-2021-605).
optimum printing temperature (23 ± 2°C). The addition Consent for publication
of PVA increased the viscosity of the bioinks; therefore,
a hydrogel construct with better shape fidelity is more The human skin samples were obtained from six consented
printable. In addition, the constructed bioinks, as cellular patients (written and verbal) and permission was obtained
skin replacement, also exhibit excellent physicochemical from each of the subjects to publish their data.

Volume 9 Issue 3 (2023) 438 https://doi.org/10.18063/ijb.677