In 1981, Dr. Hideo Kodama first proposed the 3D printing technology via fabricating a device that uses ultraviolet lights to harden polymer and create solid objects (2). On this basis, Charles Hull invented the first 3D printer (the stereolithography machine, SLA) in 1983 (3). Then, the selective laser sintering (SLS) technology was developed by Dr. Carl Deckard in 1987. One year later, there was the first rapid prototyping printer entitled SLA-1 appeared in the commercial market. In 1989, Scott Crump invented fused deposition modeling (FDM), popularly used for polymeric materials. Subsequently, other technologies such as inkjet printing, laser AM (LAM) and various subsequent methods were introduced. Today, the 3D printing industry leaders are two famous companies, 3D Systems and Stratasys (4–6). With the development of 3D printing technology, Swiss scientists fabricated customized bioresorbable airway stents with elastomeric properties in 2021 (7). Figure 1 schematically represents the 3D printing history and its achievements in the medical field.

A brief overview of additive manufacturing technologies is necessary to understand better the principles of 3D printing (Figure 2). The most commonly available 3D printing technologies mainly include four groups: vat polymerization-based printing, powder-based printing, extrusion-based printing, and droplet-based printing. First, vat polymerization-based printing uses a specific wavelength laser to locally cure the resin one layer at one time via generating an ultraviolet beam at the surface of a vat of photocurable resin. This technology mainly includes four modes: stereolithography (SLA), direct or digital light processing (DLP), and continuous liquid interface production (CDLP). This technology offers high geometric accuracy, but the resin material restricts its' development (Figure 2A) (8). Second, powder-based printing technologies rely on local heating to fuse thermoplastic powder made from plastic, metal, or ceramic. Powder-based printing technologies include selective laser sintering (SLS), direct metal laser sintering (DMLS), electron beam melting (EBM), and selective laser melting (SLM). To generate local heating, SLS, DMLS and SLM use laser beams directed by mirrors, whereas EBM utilizes a high-energy electron beam precisely directed by electromagnetic coils. Then, after local heating fusing a cross-section, the powder bed drops down one layer, and a new layer of thermoplastic powder is created. Despite this method can produce nearly fully dense parts, needing a higher cost and limited material availability (Figure 2B) (9). Third, extrusion-based technologies include fused deposition modeling (FDM) and direct ink writing (DIW). FDM uses thermoplastic or composite filaments (polylactic acid, acrylonitrile butadiene styrene, polyamides, polystyrene, polycarbonate), which are extruded through a hot nozzle. FDM provides high geometric accuracy and models that withstand the disinfection process in an operative setting. DIW utilizes a pneumatic or mechanical dispensing system to extrude concentrated suspensions formulated of primary material together through a nozzle or a syringe. This method is a well-known technique for obtaining ceramic pieces with complex geometry, but it is challenging to acquire highly dense pieces (Figure 2C) (10). Fourth, droplet-based printing is defined as computer-controlled non-contact pattern reproduction techniques, mainly including multi-jet modeling (MJM), wax deposition modeling (WDM), laser-induced forward transfer (LIFT), and binder jetting (BJ). The technology relies on the precise jetting of liquid droplets onto a substrate layer-by-layer manner. Although droplet-based printing allows full-color prototyping, it weakens the mechanical strength (Figure 2D) (11).

3D printing quality depends on the 3D printer and materials. The appropriate material is necessary to obtain a 3D-printed model with optimal properties. 3D printing materials for medical applications include but are not limited to polymers, metals, and ceramics (12). Of these, polymers, like polyether ether ketone or polystyrene, are those most commonly used. Because carbon-based materials are flexible and economical, they can be used to achieve desired properties. Like steel and titanium, metals have a long history of medical applications due to their strength, stiffness, and malleability. However, they tend to be more expensive than polymers and are more vulnerable to corrosion. Ceramics are insulating and resistant to thermal or corrosive degradation. However, ceramics are fragile and are difficult to reshape with their powders. Lastly, composites combine polymers, metals, or ceramics to create a material with respective properties. Today, many 3D printing materials are composites designed to acquire desired strength, flexibility, durability, and cost-effectiveness (13–15). A recent review elaborated on the advances in 3D printing composites (16).

3D printing technology involves many medical fields, including plastic surgery, medical and pharmaceutical industries, neurosurgery, and orthopedics (17–20). As the technology develops, tissue and organ printing is an emerging field that has proved valuable in surgical planning, anatomic prostheses, and trainee education (21, 22). In addition, 3D printing has become integral to pharmaceuticals. This way, drugs can be individually printed in specified doses, and the speed of drug delivery can be controlled (23, 24). What also deserves expecting part of the technology is potential applications of 3D biological printing, which have already hinted at the feasibility of biological printing artificial organs via the dispensing of cell-laden hydrogels (25).

In neurosurgery, it is hard to observe outwardly the most surgical procedures involving intricate, minute anatomical structures. Neurosurgeons rely on neuroimaging to prepare for highly customized procedures (26). Standard imaging methods include x-ray, CT, and MRI (27, 28). However, it is difficult to appreciate the 3D relations between these structures within a limited surgical area. With 3D printing technology, clinicians could acquire an effective solution. 3D printing translates anatomical structures into 3D images and fabricates physical models for preoperative planning and practice education. 3D printed materials can also be applied to the design of surgical simulations. The simulations provide a realistic scene to help surgeons rehearse operations as often as desired, reducing patients' potential harm risk (29–31). Moreover, 3D printing can be used for prototyping and producing innovative surgical devices, just like its' function in the manufacturing industry. This technology can create instruments and implants corresponding to individual patient anatomy to achieve a personalized treatment (32, 33). In research scenarios, 3D printed models can replace animals and human bodies to explore the biophysical characteristics of different conditions on tissues (34, 35). In summary, 3D printing in neurosurgery has four main areas: 1.

Creating anatomical models for surgical planning, training, and education.

Several articles have reported 3D printing in neurosurgery. For example, Kondo et al. generated rapid prototyping models of heads with unruptured cerebral aneurysms for 22 patients. The models perfectly reproduced the microsurgical anatomy and arteries (36). Later, Namba et al. successfully predetermined the optimal shape before the endovascular surgery via the 3D printer aneurysm model (37). In addition, printed head models were used to plan and develop new treatments for brain tumors. Makoto et al. successfully produced 3D printed plaster models of the brain to determine the optimal surgical strategies for skull base and deep tumors. Although there are some unpredicted problems, such as severe bleeding or tumor tissue hardness, surgeons could quickly solve the problems using a planned optimal surgical window (38). Moreover, 3D printing has proven to be a valuable tool in neurosurgical devices. 3D printing enables researchers to create printed devices for recording brain activity in noninvasive forms. For example, Troebinger et al. reduced between and within-session coregistration errors in Magnetoencephalography via 3D printed subject-specific head-casts (39). Furthermore, 3D printing could create a mold of the decompressed segment of the skull to perform cranioplasty. Many researchers used the mold as an implant created from many materials, such as titanium, acrylic, and polyether ketone (40–45). For example, Rok Cho et al. achieved cranioplasty via 3D printed porous titanium implants. The 3D-printed implants perfectly repaired skull defects without specific complications and dead space (46). Similarly, advances in 3D printing technology have revolutionized the treatment of craniosynostosis. Several articles have demonstrated the potential benefits of 3D printing in craniosynostosis, such as simplifying surgical procedures and specifying personalized templates. However, the literature is still in the validation stage, and more extensive case-series studies are needed to illustrate this approach's efficacy further. Modeling techniques, implant cost, and long-term skull fitness must also be improved (47). In scientific research, Kolli et al. used 3D printed models to research the effect of varying hemodynamic conditions on fractional flow reserve. The result shows that increased aortic pressure reduced fractional flow reserve value in stenosis for vascular groups with or without myocardial infarction (34). These articles, when taken together, represent just a part of aspects. With the fast development of the technologies, more and more novel applications of 3D printing have come out in practice (31).

There are several limitations to the widespread application of 3D design and printing in neurosurgery: 1.

There is a speed limitation. Because printers need a long time to build 3D models, some acute diseases such as intracerebral hemorrhage have no time to wait to achieve 3D models (48). Although some companies claim that their printer combines the benefits of good printing speed and high resolution, the practicability needs to be verified in further clinical studies (49).

3D Slicer, a multiplatform software that runs on personal computers, can directly visualize the patients' anatomy with various imaging techniques (51). It enables the fusion of anatomical data and functions and provides various generic and specialized tools for processing and multimodal analysis (Table 1). David Gering first proposed the prototype of Slicer in his master's thesis in 1999, based on the experience of earlier research groups at the Massachusetts Institute of Technology and the surgical planning laboratory of the Brigham and Women's Hospital in Boston. Subsequently, Steve Pieper served as the lead architect of Slicer, commercializing the 3D Slicer to meet the requirements of industrial-grade installation packages. The development of 3D Slicer has been followed since 1999 by the Surgical Planning Laboratory, led by Ron Kikinis. Today, 3D Slicer is a collaborative effort of professional engineers, algorithm developers, and applied scientists. Companies like Isomics, Kitware, and GE Global Research have joined Slicer. The growing Slicer community has also contributed significantly to its development. 3D Slicer was initially conceived as a system for guided treatment, visualization, and analysis in neurosurgery. However, over the decades, 3D Slicer has evolved into a comprehensive platform that can be used for various clinical and preclinical research applications and non-medical image analysis (52).

The architecture of 3D Slicer follows a modular and layered approach (Figure 3). The virtual libraries such as OpenGL and hardware drivers are not packaged with 3D Slicer and are not provided by the operating system at the lower architecture level. At the level above, there are languages (primarily C++, Python, and JavaScript) and libraries (Qt, DCMTK, jqPlot) that provide higher-level functionality and abstractions (53, 54). All the external dependencies of 3D Slicer are cross-platform portable distributed under licenses fully compatible with 3D Slicer, which made it widely used in commercial or open-source products. The great advantage of 3D Slicer is its versatility because it provides a robust API (Application programming interface) for interacting with the software using self-made code in python and other programming languages. This point enables users to build new tools and applications on top of 3D Slicer.

As a free open source extensible software, the basic capabilities of 3D Slicer include visualization, registration, segmentation, and quantification of medical data (55). Moreover, 3D Slicer can be extended to enable the development of interactive and batch processing tools for various applications (56). For example, through external code, 3D Slicer enables various applications, including fiber tract, quantification, radiomics, and AR. The development of 3D Slicer cannot be separated from a community effort. Since many groups and individual users are continually improving 3D Slicer without pay through reporting software issues and providing solutions, suggesting new features, and developing new express tools.

A few decades ago, 3D Slicer was used in computer-assisted 3D planning, navigation, and intra-operative imaging (51, 57–60). In recent years, neurosurgical trends have been minimal invasiveness and maximal safety (61). However, many tools, such as neurosurgery navigation systems and intraoperative imaging techniques, tend to be expensive and thus difficult to implement in low and middle-income areas (62–64). 3D Slicer has the characteristics of novelty, easy operation, and low cost, and it can be used for diagnosis and pre-surgical planning in neurosurgery (51, 52). Some new ideas can be provided for surgeons to develop better operative procedures via combining 3D Slicer with 3D printing in neurosurgery.

Three-dimensional printing (3D printing), specific additive manufacturing, is an inexpensive and accessible fabrication technique for transforming digital objects into physical models (95). Digital models were processed using 3D Slicer software to prepare for the 3D printing. The lifelike models created by 3D printing have an obvious advantage in training and surgical planning (96). Similarly, other advantages of 3D printing can be achieved, such as researching and developing biological tissue-engineered implants.

Many research articles have made use of 3D Slicer and 3D printing. For example, Memon et al. used 3D Slicer to segment the descending aorta, renal artery, and renal anatomy to create a computer-aided image for 3D printed models. They found that pre-operative 3D printing of renal artery anatomy could help medical staff reduce contrast, fluoroscopy, and procedure time (97). Moser et al. used 3D Slicer and 3D printer to prefabricate osteosynthesis plates for maxillofacial surgery (98). Cheng et al. used 3D Slicer to design a personalized airway prosthesis and then printed it via a 3D printer (99). Xu et al. used 3D Slicer to obtain 3D airway models. Stent customizations were made based on the 3D model dimensions via 3D printing. After the printed stents were inserted, they found improved patient airway performance (100). In neurosurgery, 3D printing has been applied in skull base procedures and trauma, such as 3D printing navigation models and skull reconstruction (101–103). These examples are just the tip of the iceberg, but they demonstrate a successful combination between 3D Slicer and 3D printing in medicine. We specially design a picture to show how 3D printing and 3D slicer can improve neurosurgery research and practice (Figure 4).

Because of the above summary of 3D Slicer and 3D printing, the knowledge displayed so far is relatively professional and abstract. We specifically summarized relevant examples to increase neurosurgeons' interest and further illustrated the application of 3D Slicer and 3D printing in neurosurgery. At the same time, we drawn related videos to demonstrate the essential software operation. We hope to provide readers with an accessible introduction to the operation via these videos. It is important to note that these videos do not show the latest graphics techniques. For more advanced graphics and modeling techniques, refer to the experience shared in the 3D Slicer forum (https://www.slicer.org/). Because our paper focused on combining 3D Slicer and 3D printing in neurosurgery, we only summarized the relevant example of 3D Slicer software here. It should be noted that many software on the market can replace 3D Slicer to carry out modeling. Readers can draw inferentially from this point and use 3d printing to conduct more relevant research.

3D Slicer can assist neurosurgery, and it is currently believed that 3D Slicer provides a low-cost and simple method to improve the efficacy and safety of surgery. Although 3D Slicer is made available for free, any use, such as clinical use, is entirely the user's responsibility, and that local regulation must be observed. On the other hand, 3D Slicer combines with other emerging technologies, such as AR technology or 3D printing to promote the development of minimally invasive neurosurgery. Therefore, it is essential to develop the new capabilities of 3D Slicer, especially in developing countries. After all, frontier technologies (e.g., surgical robots, high precision stereotaxic, and neuro-navigation) will not be utilized in all areas due to economic and scientific levels differences.

As for 3D printing, many challenges remain with the rapid development of 3D printing and increasing medical applications. In current neurosurgery, speed, materials, and uncertain cost restrict the 3D printing to the experiments stage. However, we think there must be an adequate solution to this problem in the future. Because people inevitably discover ideal materials with the development of science and technology. As a novel technology in manufacturing and design, 3D printing could change the future of medicine.

In the current study, the combination of 3D Slicer and 3D printing is still in the research phase. Regrettably, most medical reports on 3D printing and 3D Slicer are experimental studies. More clinical studies and experiments are needed to acquire evidence on the utility and accuracy of these techniques. We hope this review can arouse the attention of medical staff to study 3D Slicer and 3D printing and explore more new applications, areas of cooperation, and new growth points.