Page 398 - IJB-9-2

International Journal of Bioprinting In situ 3D bioprinter for skin wound healing

clinical use as an integral basic part of our original in situ advantages of in situ bioprinting technology are presented
bioprinter will enable its serial standard production as in Figure 12.
well as regulatory approval and certification for clinical In the end, we would like to summarize the main
use and desirable commercialization. With growing advantages of new in situ bioprinter as compared with
market penetration and scaling as well as automated serial standard in vitro 3D bioprinter and with cost-effective
manufacturing, the cost for developing in situ bioprinter in situ handheld bioprinter (Table 1). In situ bioprinting
will be significantly reduced, thereby making the bioprinter technology has obvious imitations and it is useful mainly
both affordable and clinically relevant. for the treatment of skin defects and some endoscopic
To estimate the feasibility of in situ bioprinting applications. Theoretically, such robotic system could
technology using original articulated in situ bioprinter, we be useful for bioprinting in the area of extended defects
tested it on experimental animal models of wound closure. with prominent curvature. Thus, the best results can be
It have been demonstrated that in situ bioprinter enabled achieved in the treatment of skin defects in the axillary or
in situ bioprinting of original bioink with high level of interscapular regions, as well as while covering lesions of
fidelity and adhesion on the wet curved wound’s surfaces the oral mucosa or cornea. The main advantage of in situ
of breathing animals. Moreover, the dynamic observation bioprinting is that it does not need extremely expensive
of skin wound healing in control and experimental groups and labor-consuming GMP facilities as well as additional
both in rats and minipigs revealed the strong enhancing bioreactors, because the organism itself performs this
effect of in situ bioprinting of original bioink on the function.
dynamics of wound healing process: (i) Although wound Despite the fact that handheld devices can in some cases
closure was practically the same in both groups, the wound replace a complex and massive robotic system for in situ
contraction was accelerated; (ii) level of vascularization bioprinting, especially in hard-to-reach localizations (for
was increased; (iii) the inflammation was reduced and was example, articular cartilage or the terminal gastrointestinal
more modest; and finally, (iv) the manifestation of fibrosis tract mucosa), low precision, and printing resolution
during wound healing was significantly reduced. Taken significantly limit their therapeutic capabilities.
together, these observations demonstrate the positive effect
of in situ bioprinting on the dynamics and quality of skin The main task of classical in vitro bioprinting, in our
wound healing process which is in very good agreement opinion, is creating complex tubular and solid organs,
[34]
with earlier published reports . which require a combination of different types of cells
and biomaterials with the reconstruction of the complex
To understand possible mechanisms of enhancing internal structure of the parenchyma, blood vessels, and
effect of in situ bioprinting on skin would healing, two nerves. Such tissue engineering products must undergo
additional in vitro experiments were performed. In the a long cycle of post-processing maturation in a perfusion
first experiment, we used classic collagen contraction bioreactor before they can be transplanted into the
assay , but instead of conventional simple collagen patient’s body.
[35]
hydrogel, we used bioink containing collagen hydrogel,
Theoretically, it is difficult to expect an enhancement
5% platelet lysate, and human dermal fibroblasts. It was of normal regenerative processes during skin wound
demonstrated that addition of platelet lysate to collagen healing because wound healing is a very robust process.
hydrogel increasing level of collagen hydrogel contraction Moreover, it has been indeed demonstrated in this study
by human dermal fibroblasts. In the second in vitro as well as in previously published publication that in situ
[34]
experiment, it was demonstrated the significant increase bioprinting technology at least did not dramatically change
of in vitro sprouting angiogenesis from tissue spheroids or interfere with the normal dynamics of wound healing
embedded in 3D collagen hydrogel from original bioink processes (Supplementary File). Taken together, however,
with addition of 5% platelet lysate containing a lot of our in vivo and in vitro data strongly suggest a potentially
angiogenic growth factors as compared with pure collagen strong enhancement of human skin wound healing using
hydrogel “Viscoll.” These data at least partly explain the in situ bioprinting in specific cases of skin pathological
enhanced wound healing effect in vivo. Thus, it is logical to conditions. Thus, it is logical to speculate that in situ
speculate that enhancement of wound contraction in our bioprinting technology could be potentially useful as a
in vivo experiments could be explained by in situ bioprinted novel therapeutic modality for more effective treatment
hydrogel contraction induced by dermal fibroblasts.
and enhancement of wound healing processes in different
The possible mechanisms of enhanced skin wound types of skin pathologies, such as burns, diabetic foot ulcer,
healing by employing in situ bioprinting technology are or certain genetic skin diseases (especially, for example,
summarized in the scheme presented in Figure 11. The epidermolysis bullosa).

Volume 9 Issue 2 (2023) 390 https://doi.org/10.18063/ijb.v9i2.675