**3. Applications**

**Figure 10.** Steps 11–12: Creating a 3D volume using ModelMaker tool

**Figure 9.** Steps 9–10: Continue labelling the region of interest.

124 3D Printing

**Figure 11.** Step 15: Importing the model to Meshmixer software.

The following sections will describe in details the following applications: Patient Education (Section 8), Healthcare Professional Education (Section 3), Intervention Planning (Section 4), Other Applications: Implants (Section 5.1) and (Tissue Engineering) (Section 5.2).

#### **3.1. Patient education**

Guidance from both the American Medical Association [25] and the General Medical Council in the UK [26] strongly advocates a collaborative approach by physicians with their patients. It is vital that patients are provided with the relevant knowledge allowing them to engage fully in their care and to give their informed consent to treatment [27]. Information that should be given includes an explanation of the clinical condition, the proposed procedure including the anticipated post-procedural course and its benefits, risks and alternatives [27]. This information is usually communicated verbally, sometimes with the aid of diagrams or showing patients' their 'scan'. However, physicians and surgeons undergo years of training in normal human anatomy and pathology to develop an understanding of disease processes. Diseases are assessed by increasingly complex imaging modalities such as multi-phase contrast enhanced computed tomography and multisequence magnetic resonance imaging. It also takes many years to understand the vast amount of information presented in such 2D images and then conceptualise them in 3D. Consequently, patients find medical images difficult to interpret and do not enhance understanding [2]. Although many patients access additional information about their condition on the internet, this information is also often of poor quality [28].

performing a laparoscopic pyloromyotomy surgical procedure for hypertrophic pyloric stenosis, a common neonatal condition. There was a significant improvement in Global Operative Assessment of Laparoscopic Skills and Task Specific Assessments. Users felt the model accurately simulated a laparoscopic pyloromyotomy and would be a useful tool for beginners [33].

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Use of 3D printing is being explored for planning radiological and surgical intervention in many body systems. For example, a systematic review of 3D printed kidney models found an excellent demonstration of 3D relationships between renal tumours and adjacent anatomical structures and encouraging findings with regards to the role in surgical planning [34] Similarly, in the liver a systematic review of 3D printing has found that models have served as valuable tools in preoperative planning of surgical or interventional procedures for treatment of malignant hepatic tumours [35]. However, there are few quantitative studies and further studies with inclusion of more cases are needed [34]. 3D-printed spine models have been shown to be useful in preparing for complex spinal surgery. Using 3D-printed spine models for preparation has been reported to allow successfully performance of complex en bloc resections of primary cervical tumours [36]. In addition to open surgical procedures, 3D printing has been reported useful for planning minimally invasive and particularly endovascular interventional radiology procedures. For example; 3D-printed aortic have been used for design, planning, and/or optimization of fenestrated stent grafts [37], intracranial arteriovenous models have been found to be beneficial for radiosurgery treatment planning [38] and 3D printed models have been used to plan embolization aneurysms with challenging

anatomy in the splenic artery [39] and arteriovenous malformations in the brain [40].

through the design of bespoke external fixations for tibial fracture reduction [47].

namely titanium and polyether ether ketone (PEEK) [41].

The most common medical application of 3-D printing is surgical guides—patient specific templates used intraoperatively to guide drilling or cutting. Using a guide specific to the patient has been shown to systematically reduce the operation time, as well as improved clinical outcomes in orthopaedic and maxillofacial surgery [41]. Another increasingly common methodology is the presurgical contouring or shaping of implants using 3D printed anatomical representations, as opposed to during the surgery itself [42, 43]. This is of particular interest in maxillofacial surgery, where a number of studies have shown reduced surgery time and improved surgical outcomes [44–46]. Similarly, bespoke 3D printed tools have been applied post surgically,

3D printed objects can also be directly implanted into the patient to further take advantage of the ability to create bespoke, precise models. Patient specific implants (PSI) and have seen increasing interest in recent years, with numerous implants receiving FDA clearance in the first half of 2018 alone, in the wake of publication of the FDA guidance on additive manufacturing [48]. Biocompatibility is one of the major challenges of these implants, and has the devices are often made from materials which have received clinical approval previously,

**3.3. Intervention planning**

**3.4. Implants**

3D printed models are proving a useful aid enhancing patient understanding of their disease. In complex diseases, replicas of the area of interest which patients can see and manipulate are thought to help understanding of the relative locations of anatomical structures, the specific areas of abnormality and the degree to which they are abnormal and what a proposed treatment (e.g. surgery) would entail [2]. A study of more than 100 parents of children with congenital heart disease in which patient-specific 3D printed models of the disease were produced and used during outpatient consultations found that 3D printed models can enhance engagement with parents and improve communication between cardiologists and parents, potentially impacting on parent and patient psychological adjustment following treatment [29]. A similar study has shown statistically significant improvements in confidence, knowledge and satisfaction amongst adolescents after consultations in which the main features of their congenital heart disease was presented using a 3D printed heart model based on their medical imaging data [29]. Similar data exists for other organ systems too. For example, a study of 7 children and 14 parents found that 3D printed patient specific livers models significantly improved parental understanding of basic liver anatomy and physiology, tumour characteristics, the planned surgical procedure, and surgical risks [30].

#### **3.2. Healthcare professional education**

3D printing is useful for education of healthcare professionals from undergraduate to expert level. It has been shown that complex anatomy is better understood from physical 3D models than 2D images. 3D printed models of segmental liver anatomy are superior to 3D virtual and 2D images for teaching anatomy and preparing for surgery [4]. The days of the traditional method of teaching surgeons and other interventional physicians known as "See One, Do One, Teach One" are gone. This method is no longer ethical or applicable mainly because of concerns for patient safety [31]. It has been replaced with competency-based training. Part of this change has been adoption of simulation-based education [32]. 3D printing can provide high fidelity and realistic models for simulation of procedures. There are numerous reports of 3D printing for simulation. For example, a recent study used box trainers and 3D-printed stomachs to assess medical students, general surgery residents, and adult and paediatric general surgeons performing a laparoscopic pyloromyotomy surgical procedure for hypertrophic pyloric stenosis, a common neonatal condition. There was a significant improvement in Global Operative Assessment of Laparoscopic Skills and Task Specific Assessments. Users felt the model accurately simulated a laparoscopic pyloromyotomy and would be a useful tool for beginners [33].

#### **3.3. Intervention planning**

It is vital that patients are provided with the relevant knowledge allowing them to engage fully in their care and to give their informed consent to treatment [27]. Information that should be given includes an explanation of the clinical condition, the proposed procedure including the anticipated post-procedural course and its benefits, risks and alternatives [27]. This information is usually communicated verbally, sometimes with the aid of diagrams or showing patients' their 'scan'. However, physicians and surgeons undergo years of training in normal human anatomy and pathology to develop an understanding of disease processes. Diseases are assessed by increasingly complex imaging modalities such as multi-phase contrast enhanced computed tomography and multisequence magnetic resonance imaging. It also takes many years to understand the vast amount of information presented in such 2D images and then conceptualise them in 3D. Consequently, patients find medical images difficult to interpret and do not enhance understanding [2]. Although many patients access additional information

about their condition on the internet, this information is also often of poor quality [28].

characteristics, the planned surgical procedure, and surgical risks [30].

**3.2. Healthcare professional education**

126 3D Printing

3D printed models are proving a useful aid enhancing patient understanding of their disease. In complex diseases, replicas of the area of interest which patients can see and manipulate are thought to help understanding of the relative locations of anatomical structures, the specific areas of abnormality and the degree to which they are abnormal and what a proposed treatment (e.g. surgery) would entail [2]. A study of more than 100 parents of children with congenital heart disease in which patient-specific 3D printed models of the disease were produced and used during outpatient consultations found that 3D printed models can enhance engagement with parents and improve communication between cardiologists and parents, potentially impacting on parent and patient psychological adjustment following treatment [29]. A similar study has shown statistically significant improvements in confidence, knowledge and satisfaction amongst adolescents after consultations in which the main features of their congenital heart disease was presented using a 3D printed heart model based on their medical imaging data [29]. Similar data exists for other organ systems too. For example, a study of 7 children and 14 parents found that 3D printed patient specific livers models significantly improved parental understanding of basic liver anatomy and physiology, tumour

3D printing is useful for education of healthcare professionals from undergraduate to expert level. It has been shown that complex anatomy is better understood from physical 3D models than 2D images. 3D printed models of segmental liver anatomy are superior to 3D virtual and 2D images for teaching anatomy and preparing for surgery [4]. The days of the traditional method of teaching surgeons and other interventional physicians known as "See One, Do One, Teach One" are gone. This method is no longer ethical or applicable mainly because of concerns for patient safety [31]. It has been replaced with competency-based training. Part of this change has been adoption of simulation-based education [32]. 3D printing can provide high fidelity and realistic models for simulation of procedures. There are numerous reports of 3D printing for simulation. For example, a recent study used box trainers and 3D-printed stomachs to assess medical students, general surgery residents, and adult and paediatric general surgeons Use of 3D printing is being explored for planning radiological and surgical intervention in many body systems. For example, a systematic review of 3D printed kidney models found an excellent demonstration of 3D relationships between renal tumours and adjacent anatomical structures and encouraging findings with regards to the role in surgical planning [34] Similarly, in the liver a systematic review of 3D printing has found that models have served as valuable tools in preoperative planning of surgical or interventional procedures for treatment of malignant hepatic tumours [35]. However, there are few quantitative studies and further studies with inclusion of more cases are needed [34]. 3D-printed spine models have been shown to be useful in preparing for complex spinal surgery. Using 3D-printed spine models for preparation has been reported to allow successfully performance of complex en bloc resections of primary cervical tumours [36]. In addition to open surgical procedures, 3D printing has been reported useful for planning minimally invasive and particularly endovascular interventional radiology procedures. For example; 3D-printed aortic have been used for design, planning, and/or optimization of fenestrated stent grafts [37], intracranial arteriovenous models have been found to be beneficial for radiosurgery treatment planning [38] and 3D printed models have been used to plan embolization aneurysms with challenging anatomy in the splenic artery [39] and arteriovenous malformations in the brain [40].

The most common medical application of 3-D printing is surgical guides—patient specific templates used intraoperatively to guide drilling or cutting. Using a guide specific to the patient has been shown to systematically reduce the operation time, as well as improved clinical outcomes in orthopaedic and maxillofacial surgery [41]. Another increasingly common methodology is the presurgical contouring or shaping of implants using 3D printed anatomical representations, as opposed to during the surgery itself [42, 43]. This is of particular interest in maxillofacial surgery, where a number of studies have shown reduced surgery time and improved surgical outcomes [44–46]. Similarly, bespoke 3D printed tools have been applied post surgically, through the design of bespoke external fixations for tibial fracture reduction [47].

#### **3.4. Implants**

3D printed objects can also be directly implanted into the patient to further take advantage of the ability to create bespoke, precise models. Patient specific implants (PSI) and have seen increasing interest in recent years, with numerous implants receiving FDA clearance in the first half of 2018 alone, in the wake of publication of the FDA guidance on additive manufacturing [48]. Biocompatibility is one of the major challenges of these implants, and has the devices are often made from materials which have received clinical approval previously, namely titanium and polyether ether ketone (PEEK) [41].

Using custom implants are widely accepted in maxillofacial and dental reconstruction surgery [49], in part due to the complexity of the bone and soft tissue reconstructions required. Titanium meshes have been used to create support patches to aid the repair of significant skeletal lesions [50], and splints for mandibular reconstructions [51–54]. Bespoke implants have helped reduce post-operative cosmetic deformities, which are commonly associated with these surgeries [55].

most complicated and expensive part of the treatment process, the increase in pre-surgical time may outweigh some of the costs saved in reducing surgery. Detailed cost effectiveness studies, which consider the increase in manufacturing capabilities and pre surgical time, as well as the reduction in operation time and improved patient outcomes, are necessary to truly evaluate the impact of 3D printing on healthcare costs. Improving the segmentation and model design stages of the pipeline will strengthen the case for 3D printing as a cost effective healthcare technology and are therefore crucial areas of research. For example, when stateof-the-art convolutional neural networks for automatic organ segmentation are packaged for non-expert users [65] model production time may decrease. A final consideration is the range of materials available for 3D printing. Currently materials often lack the ability to mimic both the mechanical and imaging (ultrasound, optical, electrical and X-ray) properties of biological structures. Tuning the electrical or optical properties during phantom construction has been demonstrated in rigid plastic, are not readily transferrable to flexible materials. Further the choice between these properties is mutually exclusive, as the additives used control one property change the other [66–70]. Multimodal phantoms are an area of active research and gel wax which can be tuned to have specific optical and ultrasound imaging properties looks

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Obtaining regulatory approval has been previously outlined as a significant barrier for the widespread implementation of 3D printing technologies in medicine [72]. While these challenges are still largely in place, the publication of the FDA guidance [48] has shown a clear pathway for full regulatory approval with these devices, with over 100 devices having under-

3D printing is permeating nearly every aspect of medicine from education, from before treatment begins in improving education and communication, through to improving surgical planning and reducing surgery times. As the technology becomes ubiquitous, there is increased demand for extracting the relevant anatomy from medical imaging data. This places further emphasis on the tools used to automatically create representative geometry and process them in a form, which is ready to be printed. There is of course, further emphasis on demonstrating the reliability of the technologies themselves, to reduce the time taken to produce the models, and the level of expertise to use them. The review presented here gives an overview of the myriad applications of 3D printing in medicine. The workflow to create the anatomical models along with a worked example would be helpful to medical and surgical students who need access to anatomical models, and also to students from associated fields who wish to

This work was supported by Medical image computing for next-generation healthcare technology grant [EP/M020533/1], British Society of Interventional Radiology Bursary Knowledge

gain a hands-on understanding of surgical training and planning.

to be a promising material [71].

gone pre-market approval.

**Acknowledgements**

**5. Conclusion**

The most common PSI are those created for cranioplasty to restore cranial anatomy either after surgery or repair cranial defects, as opposed to the standard treatment of autologous bone. Implants constructed out of titanium, PEEK and polymethylmethacrylate (PMMA) have all been successfully implemented surgically, and the process is becoming common practice in a number of centres [56–58]. Overall a review of custom cranial implants found the all were found to accurate and reduce operating room time, with the overwhelming majority demonstrated improvement in clinical outcomes, arising from the improved anatomical verisimilitude [41].

Neurosurgery also has the potential to benefit from 3D printing due to complexity of the anatomical considerations, with meticulous planning required due to the associated risks. Therefore a reduction of surgery time would be a considerable benefit in these cases [59]. Xu et al. [60] fabricated a 3D titanium alloy axial vertebral body that was implanted for upper cervical spinal reconstruction following a C2 Ewing sarcoma resection. A bespoke vertebral body has also been successfully implanted for reconstruction after removal of a T9 Primary bone tumour [61].

Beyond reconstructing bone and rigid structures, 3D printing methods have been developed to create bioresorbable structures, which can be used as temporary stents and splints [62, 63]. For example, a bespoke bioresorbable airway splint was successfully implanted into a child with tracheobronchomalacia [8, 64].

#### **3.5. Tissue engineering**

There are numerous applications for 3D printing technology being developed. A promising area for the integration of 3D printing technology is tissue engineering. Tissue engineering is set to provide a solution to the unmet demand for tissues and organs for regenerative medicine. This will be achieved using a combination of stem cell, bio-materials, and engineering technologies. Experts in this field believe radical improvement to tissue engineering could come from 3D printing [8]. One main problems with the synthetic scaffolds currently used is the inability to adequately mimic in vivo microarchitecture. Advances in 3D printing technology may allow production of scaffolds, which do not suffer from this problem [8].
