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

even certain improvement in the dynamics of this process strongly suggests that in situ bioprinting could be used as a
novel therapeutic modality in wound healing.

Keywords: In situ bioprinting; Wound healing; Bioink; Collagen hydrogel

1. Introduction 2. Materials and methods
Bioprinting is defined as a robotic layer by layer or additive 2.1. Hardware
biofabrication of functional tissue and organ constructs from The in situ printing scheme on a living organism includes
living cells and biomaterials (usually hydrogel) according to a robotic arm KUKA Sunrise Cabinet (KUKA, Germany)
digital model [1-6] . To perform bioprinting, it is necessary to that performs flexible programming in a high-level Java
have digital model of tissue and organ construct, bioink, or language (Figure 1). An extruder based on an electric
hydrogel loaded with living cells and bioprinter [7-9] . Due to its motor for hydrogel extrusion was used, since it is more
relative anatomical and histological simplicity, bioprinting convenient to use and does not require a compressor for
of human skin became one of most popular topics in the compressed air. In addition, the scheme uses a real-time
rapidly emerging bioprinting research field [10-12] . There are breathing skin displacement sensor, a robot controller
two main approaches in skin bioprinting technology: (i) In and a personal computer (PC) (Figure 2). In this case,
vitro bioprinting and (ii) in situ bioprinting. In the first case, the computer and the end effector are connected through
skin construct must be at first bioprinted in clean room or in USB, as well as the computer and the robot controller are
so-called good manufacturing practice (GMP) facilities and connected through TCP/IP protocol.
during post-processing, bioprinted skin constructs must
undergo accelerated tissue maturation in specially designed The compact structure of the end effector consists
bioreactor [13-15] . In case of so-called in situ (or in vivo or of a cooling system, a controller of the end effector, a
intraoperational) bioprinting, biofabrication of human skin Fishman dispenser, and a biomaterial (Figure 3A). The
could be performed directly on the patient body in operating compactification of the technical solution was achieved
room and it does not require GMP facilities. Moreover, by placing the entire electrical part on the end effector in
human body will serve as some sort of bioreactor, and thus, the control unit. All electrical components, such as voltage
there is a need in specially designed bioreactor. Thus, in situ converters, a stepper motor control driver, and a control
skin bioprinting has certain advantage and represent a cost- microcontroller of the end effector, were attached to the main
effective alternative as compared with more conventional body of the control unit. The block was closed with a lid from
in vitro skin bioprinting [16-21] . Robotic bioprinter is a key above (Figure 3B), which provided the protective properties
element of bioprinting system. There are already several of electrical components from external environmental
dozen companies producing commercial in vitro three- influences. The housing and holder of the dispenser itself,
dimensional (3D) bioprinters and even first attempts to which attached the end effector to the flange of the robot
[22]
develop original custom made in situ bioprinter in academic (Figure 3B), was made by FDM using the Ultimaker 2 3D
setting [23-25] but, to the best of our knowledge, there are printer (Ultimaker B.V., Netherlands). The structure also
commercially available in situ bioprinter. On the other hand, includes several programmable devices: A robot controller,
there is a growing interest to develop relatively cheap and an end effector, and a PC. At the same time, it is worth
affordable in situ handheld printers [26-30] which, however, noting that communication and management of all devices
are inferior option because they are not robotic driven and in the system were facilitated with the help of a PC.
thus do not follow specially designed digital models. The The choice of the dispenser is due to the fact that it
purpose of this work was to describe the design, fabrication, has already been used in the 3D bioprinter Fabion (3D
and initial in vitro and in vivo testing of in situ 3D bioprinter. Bioprinting Solution, Russia) and has proven itself to be
To the best of our knowledge, this is the first description of a convenient and reliable dispenser of biomaterials. An
commercially available commercial articulated collaborative important advantage is the possibility of flexible controlled
3D bioprinter suitable for in situ skin bioprinting. Pre-clinical material supply. The stem tip has a screw thread into
testing on specially designed animal models of human skin which the syringe piston is screwed, which allows both
diseases and sequential certification and regulatory agencies extrusion and suction of the material and is very important
approval for clinical use will enable highly desirable clinical when working with viscous materials having inertia. The
translation and commercialization of this technology. dispenser squeezes out the material using a stepper motor,

Volume 9 Issue 2 (2023) 381 https://doi.org/10.18063/ijb.v9i2.675