Page 65 - IJB-10-5

International Journal of Bioprinting Medical regenerative in situ bioprinting

used a stomach model to demonstrate the feasibility of digital light-processing in situ 3D bioprinting, leveraging
the printing system and indicated further optimization its high penetration to induce photo-crosslinking and
of the printing platform is necessary to achieve better in in situ polymerization of the bioink. In another study,
vivo bioprinting. Several optimization strategies have Urciuolo et al. implemented bio-orthogonal two-
45
been proposed, such as reducing the platform size to photon photo-polymerization of polymers (Figure 4C).
match the size of the endoscope before integrating into They demonstrated that photosensitive biopolymers,
the endoscope and in situ real-time monitoring system. consisting of cell-laden branched polyethylene glycol
In addition, the alginate/gelatin bioink can only form (PEG) and gelatin, can generate newly formed myofiber
stable structures at low temperatures; the use of Ca bundles in mice, compatible with a functional vascular
2+
as a crosslinking agent can affect cell activity; and other network. Notably, minimally invasive in situ bioprinting
gel systems should be explored for repairing gastric wall employing SLA is constrained by the requirement of
damage. Shi et al. added magnetic complexes to gelatin/ photo-crosslinkable bioinks and the effects of printing
92
sodium alginate hydrogels, which have the opposite charge depth on the printing process. Another strategy of in situ
to gastric juices. This approach increased the curing in bioprinting involves external ultrasound-mediated sound-
the acidic environment of gastric juices without requiring sensitive bioink polymerization to achieve high-resolution,
external conditions. By dispersing magnetic complexes in non-invasive in situ printing deep within the body. The
94
the hydrogel, an external magnetic field can be applied to ultrasound-induced polymerization process does not
precisely locate and control the position of the hydrogel, damage the body, and ultrasound can also control the
thereby achieving the sealing of gastric perforations. The microstructure and pore size of the scaffold. Moreover, the
practicability of the printing method was validated in a pig system can also be used to achieve continuous drug release
model with an artificially perforated stomach, while the by regulating the induction time.
biosafety of the ink was confirmed in a rat model. Zhou et
al. developed a ferromagnetic soft catheter robotic system 2.3.2. Real-time monitoring of the printing process
60
for minimally invasive in vivo printing with a magnetic In minimally invasive surgery, the patient’s anesthetized
drive and assessed its performance in a pig tissue model deep breathing can cause incision displacement, potentially
and a live rat liver (Figure 4B). Nonetheless, the minimally leading to misalignment with the robot’s remote motion
invasive surgical method is still in its early stages. It is center. This misalignment can increase tissue stress and the
necessary to miniaturize the device to fit narrow spaces risk of postoperative hernia. Therefore, it is necessary to
in the body and develop closed-loop systems for real-time monitor and adjust the small incision on the patient’s body
38
imaging combined with machine vision and structured in real time. In an earlier study, Zhao et al. developed
light to enhance the accuracy of printed structures. Yang et a seven-axis robot-assisted bioprinting system that can
al. integrated micro-CT into a ferromagnetic soft catheter actively control the alignment of the remote motion center
93
robot for printing path scanning and planning, as well as with the incision. On this basis, an adaptive closed-loop
printing irregular complex structures. Electroactive bioinks minimally invasive in vivo 3D printing strategy based on
were printed in a living rat model of partial hepatectomy, precise incision positioning is proposed, incorporating
and the results demonstrated that the printed scaffolds accurate positioning and attitude estimation through
95
significantly promoted tissue regeneration. However, the binary color ring array labeling. This strategy enables
equipment used in this ferromagnetic soft catheter robot notch sensing and robot printing to constitute a closed-
is complex and expensive. Based on simple mechanical loop control system, facilitating adaptive calibration.
engineering design principles, Shi et al. developed a 2.4. Vascularization of bioprinted structures
74
flexible robotic arm for in vivo bioprinting. However, the Adequate vascularization is essential for promoting tissue
disadvantage of this flexible robot arm is its requirement defect repair, as the microvasculature provides nutrients
for complex control and software tracking to effectively and oxygen to tissues and promotes metabolism. 96,97 For
plan the printing path. in situ 3D-bioprinted structures, there are currently two
In vivo scaffold printing typically involves light-based ways to induce vascular tissue formation: (i) growth factor-
non-invasive polymerization, but this approach is mainly induced vascularization and (ii) microporous structure-
limited to superficial tissues. Chen et al. developed a guided vascularization. Some studies have demonstrated
44
minimally invasive in situ printing system based on digital that copper-epigallocatechin gallate (Cu-EGCG) promotes
near-infrared light polymerization, demonstrating the the secretion of growth factors from vascular endothelial
98
ability to construct auricle structures in vivo. Similar to UV cells. Hu et al. prepared an extracellular matrix (ECM)-
and blue light, near-infrared light can also induce photo- based 3D-bioprinted scaffold loaded with Cu-EGCG to
polymerization. The system uses near-infrared light for promote diabetic wound healing. The ECM scaffold has

Volume 10 Issue 5 (2024) 57 doi: 10.36922/ijb.3366