Page 60 - IJB-10-5

International Journal of Bioprinting Medical regenerative in situ bioprinting

printing errors. In error compensation, a new G-code is nano-hydroxyapatite loaded with mesenchymal stromal
generated by comparing the printed structure and the 3D cells inside a murine calvaria defect model (Figure 2B).
geometry for subsequent modification to the bioprinting They also reported that the geometries of the printed cell
process. However, this compensation cannot be adjusted in scaffolds can impact the therapeutic effect in promoting
28
real time according to the printing condition, especially on bone regeneration in vivo. 80
wet or deformable surfaces. The lack of process monitoring
and immediate feedback adjustment are the main reasons 2.1.4. Applications
for low structure fidelity. For example, when bioprinting Robotic-assisted in situ bioprinting systems (RASBS)
on the surface of the human body, human breathing may are typically utilized in less mobile environments, such
cause the movement of the printing base, resulting in an as surgical operating rooms, primarily due to their
error in the printed structure. Zhu et al. introduced an considerable size and limited mobility. Various studies have
50
adaptive 3D bioprinting method that can compensate for demonstrated the successful printing of diverse tissues
66
the motion of the target surface. The method integrates and organs, including skin, 37,50 bone, 40,41,49 and cartilage.
scanning and in situ bioprinting systems, allowing real- Among various in situ bioprinting methods, extrusion-
time correction of any printing errors based on feedback based bioprinting stands out as the most widely researched
from the scanning system. Zhao et al. introduced a strategy due to its extensive selection of bioinks, low-cost
65
35
closed-loop feedback system that enables real-time motion equipment, and versatility. 28,43,81 Li et al. presented an
tracking of defects. In this system, the camera identifies the extrusion-based 3D bioprinting system featuring a robotic
location of the wound and provides feedback to the robotic manipulator to treat the swine’s bone defects. The hybrid
arm. Kucukdeger et al. proposed a closed-loop control hydrogel, consisting of sodium alginate, poly(ethylene
76
path planning method for micro-extrusion 3D printing glycol diacrylate) (PEGDA), and gelatin methacryloyl
based on the real-time perception of local nozzle offset, (GelMA), was extruded directly onto the defect area
without pre-characterization of object geometry. and photo-polymerized with an ultraviolet (UV) lamp

In addition to adaptive in situ 3D bioprinting, Yang et (Figure 2C).
al. combined optical coherence tomography (OCT) with Inkjet bioprinting has also been employed as a strategy
77
in situ 3D bioprinting to detect defects layerwise. This for in situ bioprinting. Inkjet bioprinting can deposit
approach aims to achieve process monitoring and ensure droplets in predetermined locations, 37,82 facilitating the
high structural fidelity. Several common methods used creation of gradients in cell concentrations. 39,83 Albanna
to reconstruct 3D images, such as confocal and multi- et al. developed an inkjet skin bioprinter for the
37
photon microscopes, are slow and require additional reconstruction of full-thickness wounds. The bioprinter
custom equipment. OCT imaging can be efficiently system comprises two principal components (Figure 2D):
78
integrated into in situ 3D bioprinting systems to enable (i) a 3D wound scanner and (ii) a printhead. The former
real-time and rapid analysis of the printing process. This can generate a wound map in a single continuous scan that
integrated OCT imaging system can detect print channel is subsequently compiled with additional wound maps to
blockage, uniformity of printed structures, and defects form a wound model. Likewise, the printhead consists of
caused by bubbles. Yang et al. developed a large-field, the X-, Y-, and Z-axis, with the wound area divided into
79
78
full-depth imaging system based on OCT. The system several layers on the Z-axis. They printed a fibrin/collagen
features a pre-established feedback control mechanism to hydrogel in both murine and porcine total thickness
perform secondary printing repairs on identified defects. wound models. Their results indicated that combining
This strategy of in situ defect detection and timely repair wound scanners with inkjet bioprinting improves the rate
enhances the fidelity of printed structures improves and quality of wound healing. However, as a sequential
printing efficiency, and ensures the consistency of the deposition strategy, inkjet bioprinting requires precise
printed structure. Results of finite element analysis revealed control over the deposition location, which is challenging
that this approach significantly improved the compression and time-consuming. Building on inkjet bioprinting,
modulus of the multi-layer scaffold. Christensen et al. developed an intersecting jets approach
39
Although OCT imaging features high resolution, it can that enables control over the proportion of deposited
only scan a depth of 1–2 mm below the surface of biological material at any point in the structure. However, due to
tissues. In addition to online monitoring of the quality of inherent spray inconsistencies between reactive hydrogel
the printed structure, it is also necessary to track printed solutions and suspensions, the printed structures lack
cells for bioinks that contain cells, such as using MRI to shape fidelity. To overcome this hurdle, integrating diverse
visualize specific cells deep inside the body. Keriquel et bioprinting strategies offers a promising approach for
al. demonstrated that LAB can directly deposit collagen/ achieving in situ printing. Moncal et al. proposed a hybrid
40
36
Volume 10 Issue 5 (2024) 52 doi: 10.36922/ijb.3366