Recent advances and future directions of 3D to 6D printing in brain cancer treatment and neural tissue engineering

Abstract

The field of neural tissue engineering has undergone a revolution due to advancements in 3D printing technology. This technology now enables the creation of intricate neural tissue constructs with precise geometries, topologies, and mechanical properties. Currently, there are various 3D printing techniques available, such as stereolithography and digital light processing, and a wide range of materials can be utilized, including hydrogels, biopolymers, and synthetic materials. Furthermore, the development of 4D printing has gained traction, allowing for the fabrication of structures that can change shape over time using techniques such as shape-memory polymers. These innovations have the potential to facilitate neural regeneration, drug screening, disease modeling, and hold tremendous promise for personalized diagnostics, precise therapeutic strategies against brain cancers. This review paper provides a comprehensive overview of the current state-of-the-art techniques and materials for 3D printing in neural tissue engineering and brain cancer. It focuses on the exciting possibilities that lie ahead, including the emerging field of 4D printing. Additionally, the paper discusses the potential applications of 5D and 6D printing, which integrate time and biological functions into the printing process, in the fields of neuroscience.

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

“…The ability to precisely deposit cells and biomaterials layer by layer allows for the creation of intricate vascular networks, enhancing nutrient and oxygen diffusion in larger tissue constructs. Natural polymers like alginate, collagen, and gelatin mimic the ECM, providing a supportive environment for cell growth and differentiation, while the synthetic ones such as polyethylene glycol 29 and polylactic acid (PLA) offer precise control over mechanical strength and degradation rates. 30,31…”

“…On the other hand, synthetic polymers like poly(lactic acid) (PLA), poly(ethylene glycol) (PEG), poly(glycolic acid) (PGA), poly(caprolactone) (PCL), poly(urethane) (PU) and poly(lactic- co -glycolic acid) (PLGA) have superior mechanical characteristics that are utilized in bioinks due to their tunable mechanical properties, sol–gel transition temperature and degradation rates (Table 2). 29,31 These are biocompatible materials with super mechanical features and are usually used to print hard or elastic tissues. In general, cells cannot be readily incorporated during the printing process due to the use of organic solvent for dissolution, enhanced temperature, or toxic activators.…”

“…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. 29…”

“…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.…”

“…Additionally, they offer the potential for the on-demand fabrication of patient-specific tissues for transplantation. 27–29…”