Four-dimensional bioprinting: Current developments and applications in bone tissue engineering.

4D printing has attracted academic interest in the recent years because it endows static printed structures with dynamic properties with the change of time. The shapes, functionalities, or properties of the 4D printed objects could alter under various stimuli such as heat, light, electric, and magnetic field. Briefly, 4D printing is the development of 3D printing with the fourth dimension of time. Among the fabrication techniques that have been employed for 4D printing, the direct ink writing technique shows superiority due to its open source for various types of materials. Herein, the state-of-the-art achievements about the topic of 4D printing through direct ink writing are summarized. The types of materials, printing strategies, actuated methods, and their potential applications are discussed in detail. To date, most efforts have been devoted to shape-shifting materials, including shape memory polymers, hydrogels, and liquid crystal elastomers, showing great prospects in areas ranging from the biomedical field to robotics. Finally, the current challenges and outlook toward 4D printing based on direct ink writing are also pointed out to leave open a significant space for future innovation.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/advs.202001000

Direct Ink Writing Based 4D Printing of Materials and Their Applications.

Degradable polymers are used widely in tissue engineering and regenerative medicine. Maturing capabilities in additive manufacturing coupled with advances in orthogonal chemical functionalization methodologies have enabled a rapid evolution of defect-specific form factors and strategies for designing and creating bioactive scaffolds. However, these defect-specific scaffolds, especially when utilizing degradable polymers as the base material, present processing challenges that are distinct and unique from other classes of materials. The goal of this review is to provide a guide for the fabrication of biodegradable polymer-based scaffolds that includes the complete pathway starting from selecting materials, choosing the correct fabrication method, and considering the requirements for tissue specific applications of the scaffold.

Fabrication of Biomedical Scaffolds Using Biodegradable Polymers.

Mussel-inspired agarose hydrogel scaffolds for skin tissue engineering.

In recent years, three-dimensional (3D) bioprinting has attracted wide research interest in biomedical engineering and clinical applications. This technology allows for unparalleled architecture control, adaptability and repeatability that can overcome the limits of conventional biofabrication techniques. Along with the emergence of a variety of 3D Bioprinting methods, bioinks have also come a long way. From their first developments to support bioprinting requirements, they are now engineered to specific injury sites requirements to mimic native tissue characteristics and to support biofunctionality. Current strategies involve the use of bioinks loaded with cells and biomolecules of interest, without altering their functions, to deliver in situ the elements required to enhance healing/regeneration. The current research and trends in bioink development for 3D Bioprinting purposes is overviewed herein.

https://iopscience.iop.org/article/10.1088/1758-5090/abec2c/pdf

Engineering bioinks for 3D bioprinting.

Four-dimensional (4D) bioprinting of cell-laden constructs with programmable shape-morphing structures has gained increasing attention in the field of biofabrication and tissue engineering. Currently, most of the widely used materials for 4D printing, including N-isopropylacrylamide-based polymers, are not commonly used in bioinks for cell-laden bioprinting. Herein, we propose a facile approach to create cell-laden constructs with near-infrared (NIR)-triggered shape morphing using bioinks based on alginate (the most widely used bioink for cell-laden bioprinting). Three-dimensional (3D) printed bilayered scaffolds with orthogonal structures using concentrated alginate/polydopamine (PDA) inks (14-18 wt%) showed a change in folded shape during NIR-induced dehydration. The deformation angle of the scaffold could be controlled by laser power, irradiation time and the designed patterns of the printed alginate/PDA struts in scaffolds. Then, 3D printed biphasic scaffolds consisting of alginate/PDA and cell-laden hydrogels exhibited programmable shape change under NIR stimulation. Scaffolds were able to maintain their deformed structures, and the printed cells in hydrogels retained high viability during culture in medium for at least 14 days. The biocompatible and commonly used hydrogel bioinks, NIR-triggered shape-morphing structures and maintenance of the deformed shape in the medium give this facile approach great potential for application in the field of 4D bioprinting and 4D biofabrication of artificial tissues and organs.

Cell-laden four-dimensional bioprinting using near-infrared-triggered shape-morphing alginate/polydopamine bioinks.

3D printed hydrogel/PCL core/shell fiber scaffolds with NIR-triggered drug release for cancer therapy and wound healing

Magnetically-driven drug and cell on demand release system using 3D printed alginate based hollow fiber scaffolds.

3D printed concentrated alginate/GelMA hollow-fibers-packed scaffolds with nano apatite coatings for bone tissue engineering.

The development of hydrogel based scaffold with the capability of enhanced antibacterial effects and wound healing is the promising strategy for the treatment of wound tissues with bacterial infection. Herein, we fabricated a hollow channeled hydrogel scaffold based on the mixture of dopamine modified alginate (Alg-DA) and gelatin via co-axial 3D printing for the treatment of bacterial-infected wound. The scaffold was crosslinked by copper/calcium ions, which could enhance the structural stability and mechanical properties. Meanwhile, copper ions crosslinking endowed the scaffold with good photothermal effects. The photothermal effect and copper ions showed excellent antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Moreover, the hollow channels and the sustained released copper ions could stimulate angiogenesis and accelerate wound healing process. Thus, the prepared hollow channeled hydrogel scaffold might be a potential candidate for promoting wound healing application.

3D printed hollow channeled hydrogel scaffolds with antibacterial and wound healing activities

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