3-Dimensional printing and bioprinting in neurological sciences: applications in surgery, imaging, tissue engineering, and pharmacology and therapeutics

Abstract

The rapid evolution of three-dimensional printing (3DP) has significantly impacted the medical field. In neurology for instance, 3DP has been pivotal in personalized surgical planning and education. Additionally, it has facilitated the creation of implants, microfluidic devices, and optogenetic probes, offering substantial implications for medical and research applications. Additionally, 3D printed nasal casts are showing great promise for targeted brain drug delivery. 3DP has also aided in creating 3D "phantoms" aligning with advancements in neuroimaging, and in the design of intricate objects for investigating the neurobiology of sensory perception. Furthermore, the emergence of 3D bioprinting (3DBP), a fusion of 3D printing and cell biology, has created new avenues in neural tissue engineering. Effective and ethical creation of tissue-like biomimetic constructs has enabled mechanistic, regenerative, and therapeutic evaluations. While individual reviews have explored the applications of 3DP or 3DBP, a comprehensive review encompassing the success stories across multiple facets of both technologies in neurosurgery, neuroimaging, and neuro-regeneration has been lacking. This review aims to consolidate recent achievements of both 3DP and 3DBP across various neurological science domains to encourage interdisciplinary research among neurologists, neurobiologists, and engineers, in order to promote further exploration of 3DP and 3DBP methodologies to novel areas of neurological science research and practice.

Fig. 1

Basic setup for inkjet-based and extrusion-based 3DP. Inkjet-based printing may involve electrostatic, piezoelectric or thermal element a. On the other hand, extrusion-based printing involves a piston b screw c or air pressure d

Fig. 2

Projection-based a and scanning-based b light-assisted 3D printing. A laser or other focused light source is used to solidify the photosensitive printing ink. In projection-based printing, a digital light processing (DLP) projector is used to project a 2D image of each layer onto a build stage for selective solidification of the ink as determined by the digital mask. Scanning-based 3D printing uses a computer-controlled scanning system to precisely direct the light to specific locations, allowing for the controlled solidification of the ink in a layer-by-layer fashion

Fig. 3

Different versions of light-assisted 3DP. a Laser-assisted, the beam originates from a laser source and passes through optical elements, including mirrors and lenses, to ensure precise focusing, allowing patterned printing onto a receiving substrate. b Two-photon polymerization, at specific points within the material, two-photon absorption occurs, triggering a localized polymerization reaction. c digital light processing (DLP), a digital micromirror device (DMD) or a liquid crystal display (LCD) panel projects a 2D image of the first layer onto the photosensitive ink, following which the projected light selectively solidifies the ink in the illuminated areas as dictated by the pattern of the digital image. d Stereolithography, UV light beam is focused on the printing ink composed of a photopolymerizable material for replication of the desired 3D pattern

Fig. 4

Light-assisted computed axial tomography 3DP. Computed tomography (CT) scanned images are followed to draw desired 3D pattern and précised printing design can be achieved with the help of light assisted technology

Fig. 5

Applications of 3DP in neurosurgery. Utilities include patient-specific model creation for education, predication and planning of different types of neurosurgical procedures. 3D printed micro-devices and implants have also improved neurosurgical outcomes

Fig. 6

Utilities of 3D printed fabrications in neurological sciences. Applications vary from clinical uses in creation of burr hole rings, nasal casts and implants to construction of microfluidic devices and micromanipulators for preclinical studies

Fig. 7

Applications of 3D printing in neuroimaging. Numerous possibilities for aiding microwave imaging, ophthalmoscopy, transcranial magnetic stimulation (TMS) and ultrasound imaging (TUI), magnetic resonance elastography (MRE), and high-speed angiography (HAS) have been advocated

Fig. 8

Various bioinks for 3D bioprinted hydrogels used in neurobiology. Bioinks may be based upon proteins, polysaccharides as well synthetic polymers

Fig. 9

Crosslinking strategies for bioinks in neurobiological research. Depending on the bioink used, crosslinking techniques range from enzymatic, chemical, and ionic to physical and light-aided

Fig. 10

Applications of 3DBP in neurobiology research. The multifaceted utilities of 3DBP encompass creation of cellular models of glioma, organoids and neurovasculature, study of neurogenic and synaptogenic processes, assessment of stem cell-based regenerative strategies, and manufacture of electrically conductive matrices for understanding neuronal electrophysiology