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International Journal of Bioprinting 3D printed bioactive dressings for burn wound treatment

of the dressings, and regulates the water release rate from
the hydrogel. Our findings showed that adding BBG to the
gelatin–alginate compound enables controlled water release
for up to 10 days, which is a key feature for burn wound
healing. The kinetics of water release from 3D-printed
dressings was fitted with the Higuchi model that refers
to transdermal patches and hydrogel films. Accordingly,
BBG content positively affected the in vivo wound healing
outcomes in terms of dermal/epidermal regeneration
and restoration of hair follicles in second-degree burn
wound treatment. Overall, the addition of 20 wt% BBG
promotes the functionality of 3D-printed hydrogel dressing
by synergistic effect of continuous water release from
3D-printed dressings, favorable interactions between RGD
sequences in gelatin, acidic degradation of alginate, and
cumulative release of therapeutic ions from BBG.

4. Conclusion
In this study, we developed 3D-printed bioactive wound
dressings using gelatin, alginate, and borate glass (BBG).
The incorporation of BBG improved the tensile stiffness
and cell viability of the 3D-printed dressings and regulated
water release for maintaining optimal wound moisture.
The safety and efficacy of the 3D-printed hydrogel–BBG
dressings on second-degree burn wounds was assessed in a
rat model. The 3D-printed hydrogel dressings incorporated
with 20 wt% BBG showed faster wound closure and lower
wound contracture compared to the non-printed hydrogel
Figure 10. Representative the wound tissues stained with H&E at 10× of the same composition, FDA-approved bioactive glass,
magnification. 3D-printed dressing composed of hydrogel–BBG20 and the standard of care. BBG content positively contributes
accelerated wound healing and guided the regeneration of hair follicles in to superb healing outcomes in the context of dermal/
second-degree thermal burns in a rat model. BBG guided wound healing epidermal regeneration and hair follicle restoration. The
to normal wound closure rather than wound contracture by promoting
formation of a uniform epidermal layer, regeneration of hair follicles, clinical significance of incorporating BBG into 3D-printed
and mature granulation tissue formation. Compared to the non-printed hydrogel dressings lies in bioactive formulation, non-
samples with the same formulation, the 3D-printed dressings with and adhesive contact, and ability to maintain optimal wound
without BBG improved the uniform regeneration of the dermal layer. moisture for up to 7 days. These features can potentially
Guides labeled in the figure: hyperkeratosis (black arrowhead), epidermal enhance the patient outcome by reducing the need for
regeneration (outmost layer in dark purple), dermal layer (white
arrowhead), granulation tissue (red arrowhead), hair follicle (green frequent dressing changes, minimizing the pain and the
arrowhead), and sweat glands (yellow arrowhead). risk of infection, and promote faster wound closure.
The outcome of this study provides promising insights
Our results provide substantial evidence on the effects
of BBG on mechanical properties, degradation rate, and into using bioactive formulations for 3D printing as a
versatile technology in tissue engineering and regenerative
hydration activity in 3D-printed gelatin–alginate dressings. medicine. Our study has the potential to further research on
The therapeutic ions released from BBG decreased the early more complicated bioinks incorporated with nanoparticles,
cell viability of the samples. At the same time, the favorable signaling factors, and bioactive reagents to enhance the
interactions between the acidic degradation of alginate and efficacy of bioactive hydrogel dressings. Advancements in
the presence of RGD sequences from gelatin improved the fabrication methods and 3D printing of BBG, hydrogel, and
7-day cell viability of the samples. Electrostatic interactions other bioactive materials will contribute to the development
between BBG particulates and hydrogel chains increase the of patient-specific dressings and skin substitutes, enabling
stiffness and decrease the permeability of the dressings. customizable wound healing approaches. Therefore, the
The lower permeability in 3D-printed hydrogel–BBG20 scalability and cost-effectiveness, as well as addressing the
slows down the degradation rate, increases the stability
specific regulatory requirements of 3D-printed biomedical

Volume 9 Issue 6 (2023) 146 https://doi.org/10.36922/ijb.0118