New 3-dimensional (3D) digital technologies, including 3D imaging, design, numerical simulation, and printing, have valuable potential if efficiently integrated and applied in clinical practice.1–3 The first and most important step is the acquisition of accurate image data. Acquired data are then imported and processed by specialized image-processing software packages with the aim of identifying and extracting specific tissue information. In general, it is possible to use processed medical images to design (computer-aided design [CAD]), evaluate (finite element analysis), and develop complex structures that are matched to a patient's anatomy (ie, patient-specific devices [3D printing]). This article presents the available technologies as an integrated 3D “toolkit” in orthopedics for effective diagnosis, preoperative planning, surgical simulation, surgical guidance, customized implant design, and patient-specific medical device development.
Three-dimensional Imaging and Image Acquisition
Three-dimensional imaging consists of using various available techniques, including computed tomography, magnetic resonance imaging, and ultrasound, that each can provide raw data to be subsequently used in 3 dimensions (Figure 1). Once 3D imaging has been completed, the useful information is extracted. Every image has a collection of different gray values that are depicted by a sum of pixels or voxels, otherwise known as resolution (Figure 2, Video 1). For instance, in computed tomography, the gray values are expressed in Hounsfield units (HU). By default, air corresponds to −1024 HU, water to 0 HU, and any metal to 3072 HU. Thus, very dense materials have high values and will be displayed in white, whereas less dense materials have lower values and will be displayed in black. If the threshold value is varied, materials of different densities will stand out, permitting precise differentiation of the component tissues of the computed tomography scan (Video 1).4 This process of tissue identification and classification is called segmentation, which is the isolation of all pixels of the component of interest.
A 3-dimensional volume reconstruction of a pelvic mass based on raw data provided by multi-planar computed tomography. Coronal (A), transverse (B), and sagittal (C) views and 3-dimensional (D) reconstruction of the pelvis showing the osteolytic destruction of the left hemipelvis.
A computed tomography slice image of the skull consisting of 2-dimensional pixels and 3-dimensional voxels. The larger the number of pixels or voxels, the higher the resolution (A). Different types of tissues correspond to different gray values (B).
Once the segmentation process is complete, specific algorithms translate the pixel and/or voxel spatial information into its specific 3D geometry, containing specific points, lines, and surfaces. This is known as CAD, and this 3D geometry is usually represented by triangles (Figure 3, Video 2). Thus, CAD design functions can be applied for virtual surgical simulations (measurements, cuts, geometry alterations, procedures) or for creating anatomy-specific implants, instruments, and medical devices (Figure 4).5
Geometric representation of the lower extremities using triangles. The image on the left has more triangles and thus is a more accurate (detailed) representation compared with the right.
Computer-aided design total knee replacement implants: femoral component (A), polyethylene (B), and tibial tray (C).
Three-dimensional Numerical Simulation
On the basis of the earlier segmentation process, various anatomical tissues have been differentiated and transferred to a CAD environment as different 3D geometric entities. As such, they can be easily transferred to a finite element analysis environment—a computer-based numerical simulation technique for studying the behavior of physical systems (eg, bone structures).6 Within this environment, different material properties can be assigned to different structures. For example, the cancellous and cortical parts of the femur have been differentiated via the segmentation process (Figure 5A). The next step is to apply desired forces and study the stress risers within the structure in question (Figure 5B).
Three-dimensional representation of the femoral cortical vs cancellous bone (A). Finite element analysis of a femoral model. The different regional colors correspond to different stresses (B).
Three-dimensional Printing (Also Known as Rapid Prototyping or Additive Manufacturing)
Three-dimensional printing can include either a replica of the patient's anatomy, the manufacturing of surgical instruments, or the customized implant itself. It is a fast and accurate way to develop a 3D object by building up successive thin layers of raw material. Objects are produced from digital 3D files, once they have been designed with CAD and simulated by finite element analysis. Models of any complexity can usually be built within hours, significantly reducing the product development cycle. Recent 3D printing systems can combine multiple materials, colors, and textures. Three-dimensional printing involves several established manufacturing techniques, including but not limited to stereolithography (using photosensitive liquid polymer resin that is cured and solidified by ultraviolet laser), laminated object manufacturing (using layers of paper, plastic, or metal laminates that are fused under heat and pressure), fused deposition modeling (heating and extruding small beads of fused thermoplastic materials) (Figure 6), and selective laser sintering (using granules of thermoplastic, metal, ceramic, or glass powders that are melted and bonded by a high-power laser). It also involves a multitude of experimental technologies under development, such as electron beam melting (using a computer-controlled electron beam under high vacuum to fully melt and bond metallic powder, including titanium). Each technique can be used for different clinical applications and for producing anatomical models, surgical guides, or even implants.
One of the first anatomical stereolithography models depicting part of the shoulder (A). One of the very first knee models using laminated object manufacturing techniques (B). A recent anatomical copy of a pelvic tumor using fused deposition modeling (C).
The aforementioned technologies are part of an integrated process.4 The acquisition of accurate image data is the first and most important step. Currently, most conventional hospital scanners can be used to provide medical imaging data in a DICOM (Digital Imaging and Communications in Medicine) format. Acquired data are then imported and processed by specialized image-processing software packages with the aim of identifying and extracting specific tissue information. Subsequently, CAD modeling allows the design of customized parts (ie, personalized implants and medical devices). Finite element analysis modeling allows the numerical simulation and validation of the designed parts. Rapid prototyping or additive manufacturing, both of which are commonly known as 3D printing currently, can actually build the previously designed and simulated parts. In general, virtual computer modeling and physical production can be combined as required, providing numerous advantages for achieving personalized therapy.
Clinical Applications in Orthopedics
Preoperative Visualization and Planning
The creation of 3D visualizations of the anatomy or exact 3D anatomical replicas to assist surgeons is revolutionizing the preoperative planning for many orthopedic procedures in situations ranging from complex trauma cases7–19 to elective orthopedic surgery.20–29
Trauma. Chung et al were the first to report the use of 3D printing technologies for the preoperative visualization of and planning for a calcaneal fracture9 and subsequently 4 complex distal tibial and 13 malleolar avulsion fractures.10 The mirror imaging technique was used, which in this case consisted of printing a calcaneus of actual preinjury size by using the contra-lateral noninjured side as a reference.
Consequently, preoperative planning was achieved by applying preshaped locking plates to appropriately fit the model. This allowed accurate reduction and proper plate and hole position, thereby addressing possible intraoperative challenges and complications.
Bizzotto et al7 used 3D modalities for complex articular fractures (distal radius, radial head, tibial plateau, talus, calcaneus, humeral head, and glenoid) of 102 patients from 6 hospitals. Three-dimensional printed replicas of the bones with the exact anatomy of the fracture were reproduced. These were subsequently used to establish the spatial geometry of the fragments as well as any articular displacement and to assist the surgeon in preoperatively determining the appropriate plates and screws. Additionally, the models were used when obtaining informed consent from patients and teaching medical students.
On the basis of the principles described above, including the mirror imaging technique of Chung et al9,10 and the 3D printed replicas of the fractured bones of Bizzotto et al,7 3D technology has been successfully used in the preoperative planning for clavicle fractures,12,19 complicated proximal humeral fractures,16 trimalleolar and calcaneal fractures,15 and complex acetabular fractures and pelvic surgeries.8,11,17,18
Elective Orthopedic Surgery. Three-dimensional computer-assisted preoperative planning for elective orthopedic cases has been performed in the setting of spinal disorders,20,21 sports medicine,22 adult reconstruction,23 foot and ankle surgery,24,25 pediatric orthopedics,26 and orthopedic oncology.27–29
In spinal surgery, 3D printing for visualization and preoperative planning was first reported by Mizutani et al,21 who created 3D replicas for 15 patients with rheumatoid cervical lesions. The appropriate occipitocervical angle was determined, as were the optimal contour and position of the plate-rod constructs. Li et al20 retrospectively studied 37 patients undergoing revision lumbar diskectomy who were divided into 2 groups. In the first group (15 patients), 3D lumbar vertebral models were created that accurately replicated any complex or abnormal structures and the extent of osteoproliferation. The second group (22 patients) underwent the traditional procedure without the assistance of 3D technology. Although the first group had reduced operative time and perioperative blood loss, there was no difference in the other clinical outcomes.
Sheth et al22 produced a solid 3D model of a young patient's glenohumeral joint for the preoperative planning of an arthroscopic Bankart repair. The replica was successfully used to assess the degree of bone loss (Hill-Sachs and Bankart lesions) and to determine the amount of external rotation and abduction required to engage the Hill-Sachs lesion. Furthermore, the optimal number and placement of the suture anchors required for the remplissage procedure were established.
Zerr et al23 created a 3D replica of an acetabular cup that was used as a template in the preoperative planning of a complex total hip replacement revision. This permitted gauging the sizes of the acetabular defect and the cup, optimal screw placement, and trialing of the cup to evaluate stability, coverage, and appropriate ante-version and abduction.
Giovinco et al24 used 3D printed models in Charcot-Marie-Tooth foot reconstruction surgery. These models assisted them in terms of obtaining the optimal osteotomy and joint resection, instrumentation, and placement of internal and external fixation devices.
Jastifer and Gustafson25 used a 3D printed anatomical replica for the preoperative planning for a malunited bimalleolar fracture. This replica increased understanding of the pathology, assisted with patient education, and permitted accurate preoperative measurement of the degree of corrective osteotomy and amount of bone wedge removal required.
Starosolski et al26 used 3D printed replicas to evaluate pediatric disorders. In a case of Perthes disease, 3D printing allowed accurate evaluation of the deformity and simulation of the procedure, including exact placement of implants. In addition, 3D printed models were used in cases of tarsal coalition, Blount disease, and posttraumatic physeal bars to educate both patients and residents.
The application of 3D printing technologies for preoperative planning has also been well documented in orthopedic oncology. Xiao et al28 used 3D printed replicas of cervical spinal malignant tumors for 5 patients. This enabled the surgeons to accurately localize the tumor and assess its shape, size, and relationship to surrounding structures. En bloc resection of the lesion was performed based on simulation using these models.
Ren et al27 created a 3D replica to determine the exact position of an osteoid osteoma of the calcaneus in a 17-year-old girl. A surgical plate was manufactured using 3D technology to guide the trephine to make a bone window on the lateral aspect of the calcaneus. This permitted accurate localization of the tumor, which can be challenging in the context of the complex anatomy of the foot, and complete resection of the lesion with minimal bone loss.
Zhang et al29 used a 3D printed exact anatomical replica of a pelvic osteochondroma involving the ilium, sacrum, sacroiliac joint, and lumbar spine. The model provided a precise depiction of the tumor and the adjacent soft tissues at risk preoperatively. It was also sterilized and used intraoperatively to assist the surgeons in performing a hemipelvectomy for accurate en bloc resection of the osteochondroma.
Guidance (Surgical Instrumentation)
Once 3D technology has been used for preoperative planning as described above, it can further assist in the manufacture of customized surgical guides and tools (eg, appropriate jigs and cutting tools).
Patient-specific instruments are mostly used in total knee replacement, and most companies already manufacture 3D printed patient-specific guides. Three-dimensional models of the patient's knee are printed and then disposable cutting blocks are fabricated to match and replicate the patient's knee anatomy, thus theoretically optimizing the restoration of the mechanical axis of the knee and minimizing potential surgical errors. The proposed benefits of using patient-specific instrumentation include optimized functional outcomes and reduced surgical time, blood loss, fat embolism incidents, and costs. However, the use of 3D printed cutting guides in total knee replacement has not been shown to be superior to the use of traditional techniques.30–35
In recent years, the use of 3D printed patient-specific instrumentation has expanded beyond total knee replacements. Hirao et al36 produced a custom-made surgical guide to correct a malunited pronation deformity after primary first metatarsophalangeal joint arthrodesis in a patient with rheumatoid arthritis. This provided an accurate index of rotation and alignment in complex revision fusion of the first metatarsophalangeal joint.
Storelli et al37 produced patient-specific cutting jigs for precise planning and implementation of complex multiple osteotomies in the treatment of malunited forearm fractures in children. A wedge-shaped spacer was used both preoperatively and intraoperatively to achieve optimal osteotomy size and accurately correct the rotational malalignment of these fractures.
Pérez-Mañanes et al38 used 3D printed surgical cutting guides for open wedge high tibial osteotomy in 8 patients with medial joint knee osteoarthritis. Twenty patients who underwent opening osteotomies with a traditional technique were used as controls. A patient-specific osteotomy positional guide and 3 polyhedral wedges were used to achieve the desired correction of the mechanical axis. Compared with the control group, the use of these 3D templates minimized intraoperative complications while reducing both surgical and fluoroscopic time.
Bellanova et al39 used 3D printed patient-specific instrumentation for tibial bone sarcoma resection and allograft reconstruction in 4 pediatric patients. A custom-made surgical guide was fitted to the proper position on the affected tibia for accurate tumor resection with appropriate margins. Another 3D printed guide was manufactured to cut the selected bone allograft to fit the resection gap precisely. Patient-specific guides were similarly used to achieve proper tumor resection with accurate excision margins in a case of giant invasive sacral schwannoma40 and a case of high-grade femoral osteosarcoma.41
Customized 3D printed implants have been used mainly in reconstruction surgery42–44 and orthopedic oncology.45–47 Stoffelen et al44 used 3D printing technologies for the reconstruction of severe glenoid defects after failure of total shoulder arthroplasty. A custom-made titanium glenoid implant was manufactured that, after meticulous soft tissue debridement and with the aid of bone autografts, was successfully inserted and fixed in the glenoid component of the affected shoulder.
Li et al42 and Mao et al43 used 3D printing technologies for revision total hip arthroplasties with severe acetabular bone defects (Paprosky type 3B defects). After a series of preoperative trials, custom-made 3D printed cages were used. There was 1 case of cage loosening and 1 case of dislocation among 24 patients in the study of Li et al.42 There were 2 cases of cage loosening and 2 cases of dislocation among 23 patients in the study of Mao et al.43 Mean Harris hip score significantly improved from preoperatively to postoperatively in the study of Li et al42 (36 vs 82 points) and in the study of Mao et al43 (39.6 vs 80.9 points). Thus, it can be concluded that there are promising results in terms of hip pain and postoperative complications when using custom-made cages in cases where commercially available cages do not fit well to the host bone.
Wong et al46 treated a patient with pelvic chondrosarcoma of the anterior column. First, the aforementioned mirror imaging technique and patient-specific instrumentation were used to appropriately cut the bone to resect the bone segment containing the tumor. Then, a custom-made pelvic implant designed to match the bone defect was 3D printed as a titanium monoblock. Imanishi and Choong45 used a similar technique to perform total calcanectomy and calcaneus replacement with a 3D printed titanium implant in a patient with a grade 2 chondrosarcoma of the calcaneus.
The current authors recently reported the use of 3D printed implants of the talus and calcaneus after total talectomy and calcanectomy for Ewing's sarcoma in 3 patients, who had satisfactory 1- to 2-year follow-up results.48
Xu et al47 used a 3D printed porous metal vertebral body to reconstruct the upper cervical spine of a young patient with Ewing's sarcoma after resection of the posterior elements of C2. The custom-made implant was manufactured according to a computer model, using titanium alloy powder.
Mobbs et al49 reported 2 cases in which a 3D printed prosthesis was used for reconstruction following a C1/C2 chordoma resection and a custom-made titanium fusion cage was used to treat a congenital L5-hemivertebra deformity.
The idea behind the use of custom-made 3D printed implants in orthopedic oncology is that their shape matches the excised bone, thus decreasing the stresses on the existing bone compared with conventional implants. They can also help to address the significant challenges encountered in complex oncological surgery.
The mirror imaging technique for manufacturing 3D patient-specific implants has also been applied in orthopedic trauma. Shuang et al50 used 3D printed custom-made osteosynthesis plates for 6 patients who had distal intercondylar humeral fractures. They found similar results in terms of elbow function and range of motion compared with 7 patients who were treated with conventional plates.
Orthopedic Fixators, Orthoses, and Prosthetics
Qiao et al51 used 3D printing techniques to develop a novel customized external fixator for long bone fracture reduction of the lower limb. First, 3D images of the tibial and femoral diaphyseal fractures were reconstructed through computer software and virtual reductions were simulated. Subsequently, an external fixator with the appropriate frame size, connection rods, and pins was designed and manufactured, similar to the Ilizarov model, based on the data acquired by model reduction. The custom-made external fixator was later used to treat 3 patients with diaphyseal tibial fractures, showing excellent results in terms of reduction, fixation, union, and pain.52
Raux et al53 prospectively compared custom-made orthoses for idiopathic scoliosis manufactured using a traditional plaster mold vs 3D printing among 29 children with moderate adolescent idiopathic scoliosis. Three-dimensional braces were made by optically scanning the patient, subsequently creating virtual molds, and using 3D printing for manufacturing. Each patient received 2 braces; radiographic correction and the patient's in-brace comfort were used to select the appropriate brace. Thirteen traditionally made and sixteen 3D printed braces were chosen, having comparable results in terms of correction and comfort. Although the results were comparable, 3D printing offered a less invasive and more hygienic procedure for the patient.
Dombroski et al54 used 3D printing technologies to successfully manufacture low-cost, custom-made foot orthoses. Foot molds were created from both traditional plaster casting and 3D printing methods. Custom-made orthoses were then manufactured from each mold. Arch height index was measured during 10 gait cycles for both the traditional casting and the 3D method, with similar results shown.
In a recent review, Tanaka and Lightdale-Miric55 highlighted how advances in 3D printing are altering the manufacture, customization, and accessibility of prosthetic hands for children with congenital or acquired upper extremity amputations. Because children rapidly damage and outgrow prostheses, they are ideal candidates for the currently available 3D printed devices. These custom-made prostheses are more affordable. The cost of materials for a 3D printed body-powered arm device ranges from $50 to $150, whereas the cost of a traditionally made body-powered prosthesis ranges from $4000 to $10,000. They are lightweight, easily manufactured and repaired, and designed to fit a specific size and activity.
Zuniga et al56 used low-cost 3D printed prosthetic hands for 11 children with upper-limb traumatic or congenital amputations. These hands were manufactured either via laboratory visits or from a distance. They had a significantly lower cost compared with the available mechanical and myoelectric devices and thus represent an alternative for children and families in developing countries and with limited access to health care providers.
Galvez et al57 used 3D printing to create various models from different potential donors in a case of bilateral surgical amputation in an 8-year-old child to determine the appropriate donor size for an acceptable result.
Lee et al58 3D printed a finger prosthesis for an adult patient with a right thumb amputation above the metacarpophalangeal joint. An image of the contralateral hand was used as a reference and rotated to the right side to design the appropriate thumb prosthesis.
Bioprinting is defined as the manufacture and assembly of biological materials, such as molecules, biomaterials (including scaffolds), cells, and tissues, to accomplish one or more biological functions.59 Three-dimensionally printed bio-scaffolds have been used in laboratory studies for many orthopedic conditions. Zhu et al60 3D printed porous titanium within which a gelatine scaffold was implanted together with platelets derived from platelet-rich plasma, which induced cell migration into the titanium pores. The construct thus exhibited bioactivity and was successfully implanted in rabbits, significantly accelerating bone regeneration in osteonecrosis of the femoral head.
Zhang et al61 3D printed poly-epsilon-caprolactone meniscal scaffolds that were augmented with bone marrow–derived mesenchymal stem cells. Seventy-two New Zealand rabbits were divided into 4 groups: cell-seeded scaffold, cell-free scaffold, sham operation, and total meniscectomy alone. The regeneration of the implanted tissue, the articular cartilage degeneration, and the mechanical properties of the implants were assessed by microscopic analysis at 12 and 24 weeks postoperatively. The results were significantly in favor of the cell-seeded scaffold group. The augmented poly-epsilon-caprolactone scaffolds showed increased fibrocartilaginous tissue regeneration and higher mechanical strength, thus providing a functional replacement to protect articular cartilage from damage after total meniscectomy.
Yang et al62 3D printed scaffolds composed of polylactide-co-glycolide and hydroxyapatite that were grafted with quaternized chitosan to produce biological scaffolds with increased antibacterial and osteogenic activity with advanced biocompatibility. It was shown that these scaffolds decreased biofilm formation and bacterial adhesion under both in vitro and in vivo conditions. Moreover, in experiments conducted on rats, hydroxyapatite-incorporated bioprinted scaffolds exhibited good neovascularization and enhanced tissue integration. Therefore, these results may indicate a great potential for both the prophylaxis and the treatment of bone infection.
Fedorovich et al63 3D printed heterogeneous, porous constructs by combining human osteogenic progenitors and human chondrocytes with a polysaccharide (alginate hydrogel) that promotes both osteogenic and chondrogenic differentiation. The various heterogeneous bioprinted scaffolds were then tested both in vitro and in vivo. The results indicated a stable cellular architecture of these 3D printed osteochondral grafts but also a lack of abundant osteogenic tissue formation; thus, further research is needed to improve the manufacture of cartilage implants and bone grafts.
To overcome the lack of tissue formation, Shim et al64 manufactured 3D porous structures for building osteochondral tissues by using thermoplastic biomaterial polycaprolactone (poly-epsilon-caprolactone), based on its relatively higher mechanical properties compared with hydrogel. Although these 3D scaffolds, consisting of osteoblasts and chondrocytes, were successfully fabricated and retained their viability and initial position up to 7 days after being dispensed, they were tested only in vitro; therefore, further research is necessary to prove their efficacy and potential for use for osteochondral reconstruction and cartilage regeneration in humans.