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International Journal of Bioprinting Medical regenerative in situ bioprinting

determined by the size and shape of the ice crystals during were subsequently introduced to enhance the adhesion
the freeze-drying process. Notably, the pores of the printed between the component layers. Luo et al. introduced
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structure affect tissue repair because scaffolds with good cinnamic acid groups to a polylactic acid/PEG-copolyester
porosity are conducive to oxygen transport and promote blend to induce photo-crosslinking, enhancing interlayer
cell adhesion and proliferation. Several studies have bonding, and thereby improving the printing accuracy
reported oxygen supply strategies for adding inorganic and stability of the structure.
peroxides to scaffolds, but these oxygen supply systems Overall, 4D-printed dynamic scaffolds are still in the
are limited in their ability to provide sufficient oxygen.
Wang et al. developed a self-supplying oxygen system early stages of development, with a key challenge being
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that prints photosynthetic microalgae in situ at the wound the design of materials that are both programmable and
site, thereby providing continuous oxygen for wound biocompatible. Future advancements are expected to
healing. The system could also promote cell proliferation, integrate AI or machine learning techniques to develop
migration, and differentiation under hypoxic conditions new materials, design functional structures, and optimize
and accelerate wound healing in chronic diabetic wounds. printing parameters.

3.4. Intelligent materials for 4D bioprinting 4. Future perspectives
Different soft tissue injuries require specific complex While notable advancements have been made in in situ
structures for repair. For in situ bioprinting, the surgical bioprinting, several challenges remain in promoting
site is often exposed to unavoidable damage, and cells vascularization within printed structures, automating
are lost during the implantation process. Therefore, RASBS procedures, developing highly modular designs for
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4D printing technology, which allows structures to be HISBS, and optimizing the bioink system. Printed structures
implanted into the damaged site in a compact form, has
garnered significant attention. 4D printing technology for tissue repair should promote vascularization, and in situ
combines smart materials (i.e., stimuli-responsive 3D bioprinting technology can combine multiple materials
materials) with 3D printing technology to compress 3D and cells to print complex structures, creating microchannels
structures into 1D or 2D structures in vitro and implant that promote vascularization. Microfluidic technology can
them in the body to restore programmable shapes under also be integrated, such as using a microfluidic chip needle
specific stimuli (temperature, humidity, magnetic field, to mix multiple bioinks and cells and print a scaffold with a
pH, etc.). Shi et al. developed a magnetic hydrogel specific concentration gradient.
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for treating stomach injuries that control bioink delivery For RASBS, incorporating AI could enhance path
through a gastroscope nozzle. The magnetic bioink planning to achieve more detailed and automated in situ
accumulates at the damaged site under the influence of bioprinting. For in situ bioprinting on curved and inclined
an external magnetic field, facilitating sutureless tissue planes, flexible robotic arms may represent the future
sealing. Compared to external stimuli, such as magnetic direction of development. These arms offer higher degrees
fields and high temperatures, endogenous stimuli in of freedom compared to rigid robotic arms, effectively
response to body temperature or body fluids are more mitigating the step effect caused by printing on curved
convenient and biofriendly. Hydrogels expand due to structures. In addition, machine learning algorithms can
water absorption, making them the preferred material optimize non-planar automatic segmentation, reconstruct
for 4D printing. Using water-induced programmable defects in damaged parts, and obtain print paths. In situ
deformation, Joshi et al. prepared hydrogels using bioprinting platforms can also be integrated with machine
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alginate and methylcellulose at specific ratios for different vision and depth cameras to improve recognition accuracy.
expansion rates. The hydrogels were then used to construct Traditional bioprinting technology can print in vitro and
4D-printed catheters for repairing peripheral nerves. Liu perform print quality checks, capabilities that are currently
et al. developed an amphiphilic dynamic thermosetting limited with in situ bioprinting strategies. Therefore,
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polyurethane that transitions from 2D to 1D structures in achieving in situ quality inspection and control of printed
a body temperature environment and programmatically structures is also a future development trend. There have
transforms into 3D structures upon exposure to water been studies using MRI to track printed cells and assess
after implantation in vivo. Furthermore, the material has the healing process. For evaluating the quality of printed
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water-hardening properties, suggesting good mechanical scaffolds, OCT can be used for rapid real-time imaging and
properties. The structure is printed using melt deposition process feedback control according to the monitoring data. 79
modeling, employing a layer-by-layer printing strategy
that can lead to weak interlayer bonding in the printed Considering the portability of handheld bioprinters,
structure. Thermally reversible dynamic covalent bonds such devices should be designed to be highly modular

Volume 10 Issue 5 (2024) 60 doi: 10.36922/ijb.3366