Intelligent Vascularized 3D/4D/5D/6D-Printed Tissue Scaffolds

Abstract

Blood vessels are essential for nutrient and oxygen delivery and waste removal. Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering. Additive manufacturing is a manufacturing technology that creates three-dimensional solids by stacking substances layer by layer, mainly including but not limited to 3D printing, but also 4D printing, 5D printing and 6D printing. It can be effectively combined with vascularization to meet the needs of vascularized tissue scaffolds by precisely tuning the mechanical structure and biological properties of smart vascular scaffolds. Herein, the development of neovascularization to vascularization to bone tissue engineering is systematically discussed in terms of the importance of vascularization to the tissue. Additionally, the research progress and future prospects of vascularized 3D printed scaffold materials are highlighted and presented in four categories: functional vascularized 3D printed scaffolds, cell-based vascularized 3D printed scaffolds, vascularized 3D printed scaffolds loaded with specific carriers and bionic vascularized 3D printed scaffolds. Finally, a brief review of vascularized additive manufacturing-tissue scaffolds in related tissues such as the vascular tissue engineering, cardiovascular system, skeletal muscle, soft tissue and a discussion of the challenges and development efforts leading to significant advances in intelligent vascularized tissue regeneration is presented.

Degradable biomedical elastomers: paving the future of tissue repair and regenerative medicine

“…304 Yet, when dealing with inclined or curved surfaces or structures at non-standard angles, this layering method can lead to uneven edges or misaligned layers, resulting in a “staircase effect” – minor irregularities between layers that affect overall smoothness and precision. 305 In 5D printing, adjustments to the print head and bed orientation can be more precise, showing potential in printing DBE that conform to human physiological curves. 4D printing adds a temporal dimension to 3D printing, characterized by its stimulus-responsive nature.…”

Application of 3D, 4D, 5D, and 6D bioprinting in cancer research: what does the future look like?

“…The advancements in additive manufacturing technologies have led to the emergence of 5-dimensional (5D) and 6-dimensional (6D) printing, offering innovative approaches in various fields, 88 including cancer research. These technologies extend beyond conventional 3D printing, incorporating additional dimensions to enhance the functionality and properties of printed objects.…”

“…This technology, leveraging a five-axis printing approach, enables the creation of objects with markedly improved strength and precision. 88 Such an advancement is particularly crucial in cancer research for the development of robust and accurate models of cancerous tissues, which are instrumental in deepening our understanding of cancer progression and in refining the treatment strategies. The fact that 5D technology allows the creation of curved layer surfaces with enhanced material resilience that mimic the nervous system environment more accurately contributes to overcoming the limitations of existing techniques for studying diseases associated with the brain, namely, brain cancer.…”

“…5D printing is noteworthy for its efficiency in material usage. 29,88 The ability to conserve raw materials during the printing process is a substantial benefit, especially in research environments where budget constraints are a common concern. However, the application of 5D printing in cancer research is not without its challenges.…”

4D bioprinting of programmed dynamic tissues

“…1 d). Although a number of recent reviews presented excellent discussions on 4D printing and bioprinting [ 17 , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] ], most of them only reviewed 4D bioprinting as a part of a broader topic and lacked an up-to-date and comprehensive presentation of this rapidly developing field. Besides, previously published related reviews rarely discussed the still debatable definition of 4D bioprinting.…”