Development from 4D bioprinting to 5D bioprinting: Advancements in tissue engineering and biomedical applications

Additive manufacturing, or 3D printing, has transformed tissue engineering by enabling the creation of intricate scaffolds and cell scaffold constructs that closely mimic organic tissues. This technique provides a foundation for creating structures that promote cell proliferation and tissue growth. The shift from 3D to 4D printing has introduced dynamic and time-responsive scaffolds that enhance the capabilities of tissue engineering by allowing constructs to modify their shape or function in response to environmental stimuli. These advancements are crucial for formulating adaptable treatments for human tissue regeneration. Bioprinting, a branch of 3D and 4D printing, incorporates living cells into printed constructs, resulting in cell-infused entities that harmoniously integrate with the human body. This method has considerable promise for producing live tissues; yet, both 3D/4D printing and bioprinting have technological limitations concerning precision, scalability, and functional intricacy. In response to these challenges, 5D printing has emerged as a conceptual innovation beyond traditional dimensions. In 5D bioprinting, information serves as the fifth dimension and is embedded into printed N objects along the dimensions of space and time. This supplementary information enables 5D-printed structures to interact more dynamically with their surroundings. Upon activation, this embedded information can alter ambient conditions or trigger functional responses inside printed objects, thereby enhancing the adaptability and integration with biological systems. This article presents a comprehensive analysis of 4D bioprinting methodologies in tissue engineering, followed by an exploration of the potential of 5D printing. 5D bioprinting incorporates spatial, temporal, and informational dimensions, fostering innovative prospects in biomedical applications, and advancing the creation of intelligent scaffolds and adaptive biomaterials that can transform regenerative medicine and personalized healthcare. 3DPB : Three-dimensional printing bioprinting.