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International Journal of Bioprinting Medical regenerative in situ bioprinting

vitro pre-printing and incubation requirements, reduces concise comparison of these techniques is provided in
contamination risks, and enables real-time adjustments Table 1. Herein, we shall compare the two aforementioned
according to the printed structures. Compared with in situ bioprinting systems (i.e., RASBS and HISBS) in
conventional bioprinting, the strategy can precisely match detail across multiple aspects (Table 2).
the shape of the wound, crosslink in situ for adhesion
without in vitro culture, facilitate rapid repairment, and 2.1. Robotic-assisted in situ bioprinting system
minimize fibrosis. 30–32 Furthermore, in situ bioprinting can 2.1.1. System setup
exploit the human body’s regenerative potential, providing Robotic-assisted in situ bioprinting systems (RASBS) are
the physiological environment required for scaffold an emerging method for fabricating 3D structures using
culture. In situ bioprinting systems can be divided into two software codes, reducing human intervention and ensuring
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major categories: robotic-assisted in situ bioprinting system higher printing accuracy. The key factors affecting the
(RASBS) (Figure 1A) and handheld in situ bioprinting quality of the printed structure include printing speed,
system (HISBS) (Figure 1B). RASBS can be programmed stability, and repeatable positioning accuracy. The
by computer-aided manufacturing (CAM) and usually be printing speed encompasses both the moving speed of
used in less mobile environments. This strategy has many the printhead and the extrusion speed of the material,
advantages, such as high precision, 35,36 multi-material and these parameters require optimization based on the
in situ printing for significant composite defects, and rheological properties of the material. For example, a
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compatibility with minimally invasive surgery, but is also high moving speed and low extrusion speed will produce
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time-consuming and requires sophisticated equipment.
HISBS is an alternative strategy for in situ bioprinting that discontinuous lines; a low moving speed and high
is easy to use without the need for complex equipment extrusion speed will produce clustered lines. The stability
and expertise. Although HISBS has a relatively lower of the printing structure mainly depends on the physical
printing resolution and limited multi-material processing and chemical properties of the material, highlighting
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ability due to the compromise for portability, it has the the importance of selecting the appropriate bioink.
potential to meet specific requirements of emergency Repeatable positioning accuracy sets high requirements
clinical applications. Minimally invasive in situ bioprinting for in situ bioprinting systems, necessitating robot-assisted
combines robotic assistance and human control for non- positioning combined with computer vision and sensors to
invasive printing in vivo. further improve positioning accuracy. 62
In situ 3D bioprinting has been demonstrated to Nonetheless, RASBS offers a range of advantages, such
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effectively repair tissue defects, addressing the problems of as: (i) superior printing accuracy and dexterity that are
mismatched structures from conventional 3D bioprinting crucial for achieving a precise fit with the exact shape
and reducing infection risks, while simplifying the of the wound; (ii) rapid production of complex multi-
surgical procedure. Despite existing reviews on in situ material structures, 63,64 especially in critical situations that
3D bioprinting technology, recent research has reported necessitate emergency treatment, such as in battlefield or
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new advancements in this technology, highlighting its accident scenarios; (iii) reduced human intervention,
potential to enhance tissue repair and better promote as RASBS can automate the bioprinting process using
its clinical application. These studies focus on ensuring computer-aided robotic arms and digital models; (iv)
the precise fit and mechanical integrity of structures seamless integration with minimally invasive surgical
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for irregularly shaped wounds, optimizing the printing techniques, including endoscopy, facilitating inside
path, real-time monitoring of the printing process, and body printing; (v) compatibility with process monitoring
accurately positioning and curing bioinks in deep tissues systems and machine learning techniques, 65–67 contributing
in vivo. Herein, this article reviews the utilization of in situ to error reduction during the printing process; and (vi)
bioprinting in real-time monitoring and the optimization enhanced cell viability by minimizing the exposure of
of printing performance in terms of automatic printing, printed cells to external environmental conditions, while
handheld printing, human-controlled machine assisted in the complex topological structures aid in regulating the
situ bioprinting and bioinks. spatial distribution and growth of cells.
Most reported RASBS are made up of robotic arms, 65,68–71
2. Strategies of in situ bioprinting but some automated in situ bioprinting platforms are made
The bioprinting techniques used for in situ bioprinting up of framework-based systems. 32,72 The in situ printing
include inkjet bioprinting, 37,39 laser-assisted bioprinting system based on the robotic arm can utilize either multi-
(LAB), 40,41 extrusion bioprinting, 42,43 stereolithography- axis rigid robot arms 38,73 or flexible robot arms. During
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based (SLA) bioprinting, 44,45 and electrospinning. 46,47 A the printing process, the structure is printed by computer-

Volume 10 Issue 5 (2024) 49 doi: 10.36922/ijb.3366