Stereolithographic Models and Implants

Number: 0613

Policy

Aetna considers the use of three-dimensional (3D) stereolithographic models in penile surface mold brachytherapy, plastic and reconstructive surgery experimental and investigational because such modeling has not been proven to improve surgical outcomes.

Aetna considers 3D printed cranial implant experimental and investigational because of insufficient evidence of its effectiveness.

Aetna considers the use of 3D printing of anatomic structures for pre-operative planning and other applications experimental and investigational because of insufficient evidence of its effectiveness.

Background

Stereolithography is an industrial process that uses data generated from computer-assisted design (CAD) to generate three-dimensional (3-D) models.  The data drives a laser over a bath of photosensitive resin which produces a series of stacked slices, which produce a 3-D industrial prototype or model.  This technique has been investigated in Europe, and has been used primarily by maxillo-facial surgeons to produce 3-D representations of facial bony structures using data from computed tomography (CT) or magnetic resonance imaging scans.

Stereolithographic bio-models allow visualization of the facial skeleton, and have been used in a number of particular clinical situations involving bony facial deformities.  These models have been used in the diagnosis and treatment planning of congenital, developmental and post-traumatic conditions affecting the facial region.

In particular, the models are intended to assist the maxillofacial surgeon in appreciating spatial displacements in all three dimensions and to make accurate measurement of the deformity.  The surgeon is able to practice the surgery on the model, and better determine the osteotomies and bone grafts that are required to achieve the desired results.

Proponents argue that these models can reduce operating room time and increase the accuracy of the surgical outcomes.

However, prospective clinical studies are needed to demonstrate the value of stereolithographic modeling in plastic and reconstructive surgery.  The literature on stereolithographic modeling in plastic and reconstructive surgery is limited to case reports and discussions about the feasibility of the technique.  There are no prospective studies demonstrating that the use of stereolithographic models improves outcomes of plastic and reconstructive surgical procedures.  Based on the lack of prospective clinical studies in the peer-reviewed published medical literature proving the value of stereolithographic modeling in plastic and reconstructive surgery, stereolithographic modeling is considered experimental and investigational.

As Clark and Park (2001) noted that 3-D stereolithographic models may someday have an established place in surgical planning and implant design in plastic and reconstructive surgery.  In a discussion of "future and controversies" in plastic and reconstructive surgery, the authors stated that "[u]se of stereolithography to aid in planning complex cases may become the routine."

Kakarala et al (2006) discussed the use of stereolithographic models in the assessment of new surgical techniques.  The authors explained that variable properties and limited availability are pitfalls in using cadaveric bones for implant stability tests.  Artificial bones avoid these, but tailoring them to specific studies may be difficult.  Stereolithography (SLA) techniques produce tailor-made bones with realistic geometries, but their lower Young's modulus might affect outcomes.  These researchers investigated whether implant stability and cortical strains with SLA made bones match those with stiffer artificial bones and, if not, whether a thicker cortex to compensate the lower modulus gives a better match.  Tibial trays were cemented in place and cyclically loaded while determining cortical strain and tray migration.  Permanent and cyclic migration of trays in both types of SLA model (range of 13 to 28 and 58 to 85 mum) was within the range of those in composite models (range of 4 to 62 and 51 to 105 microm).  Strains more distally were approximately inversely proportional to the material stiffness and cortical thickness of the tibiae.  The authors concluded that this first study provided a strong indication for SLA tibiae as a valid model for the biomechanical assessment of new techniques in knee surgery and compared favorably with previously utilized models.

Ozan et al (2009) stated that pre-surgical planning is essential to achieve esthetic and functional implants.  The goal of this clinical study was to determine the angular and linear deviations at the implant neck and apex between planned and placed implants using SLA surgical guides.  A total of 110 implants were placed using SLA surgical guides generated from CT.  All patients used the radiographical templates during CT scanning.  After obtaining 3-D CT scans, each implant insertion was simulated on the CT images.  Stereolithography surgical guides by means of a rapid prototyping method including a laser beam were used during implant insertion.  A new CT scan was made for each patient after implant insertion.  Special software was used to match images of the planned and placed implants, and their positions and axes were compared.  The mean angular deviation of all placed implants was 4.1 degrees +/- 2.3 degrees, whereas mean linear deviation was 1.11 +/- 0.7 mm at the implant neck and 1.41 +/- 0.9 mm at the implant apex compared with the planned implants.  The angular deviations of the placed implants compared with the planned implants were 2.91 degrees +/- 1.3 degrees, 4.63 degrees +/- 2.6 degrees, and 4.51 degrees +/- 2.1 degrees for the tooth-supported, bone-supported, and mucosa-supported SLA surgical guides, respectively.  The authors concluded that the findings of this study suggested that SLA surgical guides using CT data may be reliable in implant placement, and tooth-supported SLA surgical guides were more accurate than bone- or mucosa-supported SLA surgical guides. 

In a pilot study, Chen et al (2010) introduced a novel bone-tooth-combined-supported surgical guide, which is designed by utilizing a special modular software and fabricated via SLA technique using both laser scanning and CT imaging, thus improving the fit accuracy and reliability.  A modular pre-operative planning software was developed for computer-aided oral implantology.  With the introduction of dynamic link libraries and some well-known free, open-source software libraries such as Visualization Toolkit (Kitware, Inc., New York, NY) and Insight Toolkit (Kitware, Inc.) a plug-in evolutive software architecture was established, allowing for expandability, accessibility, and maintainability in the system.  To provide a link between the pre-operative plan and the actual surgery, a novel bone-tooth-combined-supported surgical template was fabricated, utilizing laser scanning, image registration, and rapid prototyping.  Clinical studies were conducted on 4 partially edentulous cases to make a comparison with the conventional bone-supported templates.  The fixation was more stable than tooth-supported templates because laser scanning technology obtained detailed dentition information, which brought about the unique topography between the match surface of the templates and the adjacent teeth.  The average distance deviations at the coronal and apical point of the implant were 0.66 mm (range of 0.3 to 1.2) and 0.86 mm (range of 0.4 to 1.2), and the average angle deviation was 1.84 degrees (range of 0.6 to 2.8).  The authors concluded that this pilot study proves that the novel combined-supported templates are superior to the conventional ones.  However, more clinical cases will be conducted to demonstrate their feasibility and reliability.

D'haese et al (2012) reviewed data on accuracy and surgical and prosthodontical complications using stereolithographical surgical guides for implant rehabilitation.  Only papers in English were selected. A dditional references found through reading of selected papers completed the list.  A total of 31 papers were selected; 10 reported deviations between the pre-operative implant planning and the post-operative implant locations.  One in-vitro study reported a mean apical deviation of 1.0 mm; 3 ex-vivo studies reported a mean apical deviation ranging between 0.6 and 1.2 mm.  In 6 in-vivo studies, an apical deviation between 0.95 and 4.5 mm was found.  Six papers reported on complications mounting to 42 % of the cases when stereolithographic guided surgery was combined with immediate loading.  The authors concluded that substantial deviations in 3-D directions were found between virtual planning and actually obtained implant position.  This finding and additionally reported post-surgical complications leads to the conclusion that care should be taken whenever applying this technique on a routine basis.

Ronca et al (2012) noted that the stereolithography process is based on the photo-polymerization through a dynamic mask generator of successive layers of photo-curable resin, allowing the manufactory of accurate micro objects with high aspect ratio and curved surfaces.  In the present work, the stereolithography technique is applied to produce nano-composite bioactive scaffolds from Computer Assisted Design (CAD) files.  Porous scaffolds are designed with computer software and built with a composite poly(D,L-lactide)/nano hydroxyapatite based resin.  Triply-periodic minimal surfaces are shown to be a more versatile source of biomorphic scaffold designs and scaffolds with double-Gyroid architecture are realized and characterized from morphological, mechanical and biological point of view.  The structures show excellent reproduction of the design and good mechanical properties.  Human marrow mesenchymal cells (hMSC) are seeded onto porous PDLLA composites for 3 weeks and cultured in osteogenic medium.  Presence of nano-hap seems to increase the mechanical properties without affecting the morphology of the structures.  The composite double-Gyroid scaffolds exhibit good biocompatibility and confirm that nano-hap enhances the scaffold bioactive and osteo-conductive potential.  The authors concluded that the presented technology and materials enable an accurate preparation of tissue engineering composite scaffolds with a large freedom of design, and really complex internal architectures.  They stated that results indicated that the scaffolds fulfill the basic requirements of bone tissue engineering scaffold, and have the potential to be applied in orthopedic surgery.

Morris and colleagues (2013) stated that stereolithographic (SLA) models have become a resource in pre-operative planning in maxillofacial reconstruction.  These investigators performed a defect specific analysis of the utility of SLA models.  The goal was to determine the manner in which the perceived benefit of pre-operative modeling translates to measurable clinical advantages.  Patients who underwent reconstruction of defects of the mandible or mid-face using SLA modeling between 2006 and 2011 were identified through billing records.  Based on the nature and extent of bony defect, cases requiring nearly identical reconstruction, but without modeling, were matched case-by-case for comparison.  Given the presumed efficiency of SLA modeling, a comparison of total and reconstructive operative times was performed to see if this could offset the cost of the model.  There were 10 patients each in the "model" and "non-model" group.  No significant differences were observed for total operative time between groups.  Surprisingly, the total reconstructive time was lower in the group not using SLA models (p = 0.05).  The authors concluded that SLA models provide several operative planning advantages, but did not appear to decrease operative time enough to sufficiently offset the cost of the model in this group.

Chia et al (2015) stated that 3-D printing promises to produce complex biomedical devices according to computer design using patient-specific anatomical data.  Since its initial use as pre-surgical visualization models and tooling molds, 3-D printing has slowly evolved to create one-of-a-kind devices, implants, scaffolds for tissue engineering, diagnostic platforms, and drug delivery systems.  Fueled by the recent explosion in public interest and access to affordable printers, there is renewed interest to combine stem cells with custom 3-D scaffolds for personalized regenerative medicine.  These investigators noted that before 3-D printing can be used routinely for the regeneration of complex tissues (e.g., bone, cartilage, muscles, vessels, nerves in the cranio-maxillo-facial complex), and complex organs with intricate 3-D microarchitecture (e.g., liver, lymphoid organs), several technological limitations must be addressed.  These researchers reviewed the major materials and technology advances within the last 5 years for each of the common 3-D printing technologies (Three Dimensional Printing, Fused Deposition Modeling, Selective Laser Sintering, Stereolithography, and 3D Plotting/Direct-Write/Bioprinting).  Examples were highlighted to illustrate progress of each technology in tissue engineering, and key limitations were identified to motivate future research and advance this fascinating field of advanced manufacturing.

Lee and Cho (2015) noted that many researchers have attempted to use computer-aided design (CAD) and computer-aided manufacturing (CAM) to realize a scaffold that provides a 3-D environment for regeneration of tissues and organs.  As a result, several 3-D printing technologies, including stereolithography, deposition modeling, inkjet-based printing and selective laser sintering have been developed.  Because these 3-D printing technologies use computers for design and fabrication, and they can fabricate 3-D scaffolds as designed; as a consequence, they can be standardized.  Growth of target tissues and organs requires the presence of appropriate growth factors, so fabrication of 3-D scaffold systems that release these biomolecules has been explored.  A drug delivery system (DDS) that administrates a pharmaceutical compound to achieve a therapeutic effect in cells, animals and humans is a key technology that delivers biomolecules without side effects caused by excessive doses; 3-D printing technologies and DDSs have been assembled successfully, so new possibilities for improved tissue regeneration have been suggested.  The authors concluded that if the interaction between cells and scaffold system with biomolecules can be understood and controlled, and if an optimal 3-D tissue regenerating environment is realized, 3-D printing technologies will become an important aspect of tissue engineering research in the near future.

Popescu and Laptoiu (2016) noted that SLA is a rapid prototyping (RP) process used in the medical setting.  These investigators stated that there has been a lot of hype surrounding the advantages of RP processes in a number of fields.  They evaluated the effectiveness of patient-specific surgical guides manufactured using RP in various orthopedic surgical applications (e.g., bone tissue engineering).  These researchers performed a systematic review to identify and analyze clinical and experimental literature studies in which RP patient-specific surgical guides were used, focusing especially on those that entailed quantifiable outcomes and, at the same time, providing details on the guides' design and type of manufacturing process.  The authors stated that in this field there are not yet medium- or long-term data, and no information on revisions.  In the reviewed studies, the reported positive opinions on the use of RP patient-specific surgical guides related to the following advantages: reduction in operating times, low costs, and improvements in the accuracy of surgical interventions.  Moreover, they discussed disadvantages and sources of errors that can cause patient-specific surgical guide failures.

Yuan and colleagues (2017) stated that bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction.  Autografts and allografts have been used in clinical application for some time, but they have disadvantages.  With the inherent drawback in the precision and reproducibility of conventional scaffold fabrication techniques, the results of bone surgery may not be ideal.  This is despite the introduction of bone tissue engineering that provides a powerful approach for bone repair.  Rapid prototyping technologies have emerged as an alternative and have been employed in bone tissue engineering, enhancing bone tissue regeneration in terms of mechanical strength, pore geometry, and bioactive factors, and overcoming some of the disadvantages of conventional technologies.  These researchers focused on the basic principles and characteristics of various fabrication technologies (e.g., SLA, selective laser sintering, and fused deposition modeling) and reviewed the application of RP techniques to scaffolds for bone tissue engineering.  The authors concluded that in the near future, the use of scaffolds for bone tissue engineering prepared by RP technology might be an effective therapeutic strategy for bone defects.  Moreover,, they noted that for further development, RP-based 3D biochemical printing technology and nanotechnology will be key in overcoming the “development bottleneck”.  Ultimately, it is of great significance to choose proper biomaterials, preparation processes, and scaffold design.  Bone tissue engineering will encounter challenges in the innovation of materials and techniques, optimization of scaffolds, treatment of interfaces, and incorporation of biologically active factors.

Guillaume and associates (2017) noted that fabrication of composite scaffolds using SLA for bone tissue engineering has shown great promises.  However, in order to trigger effective bone formation and implant integration, exogenous growth factors are commonly combined to scaffold materials.  These researchers fabricated biodegradable composite scaffolds using SLA and endowed them with osteo-promotive properties in the absence of biologics.  First, these investigators prepared photo-crosslinkable poly(trimethylene carbonate) (PTMC) resins containing 20 and 40 wt% of hydroxyapatite (HA) nanoparticles and fabricated scaffolds with controlled macro-architecture.  Then, they conducted experiments to investigate how the incorporation of HA in photo-crosslinked PTMC matrices improved human bone marrow stem cells osteogenic differentiation in-vitro and kinetic of bone healing in-vivo.  These investigators observed that bone regeneration was significantly improved using composite scaffolds containing as low as 20 wt% of HA, along with difference in terms of osteogenesis and degree of implant osseo-integration.  Further investigations revealed that SLA process was responsible for the formation of a rich microscale layer of HA corralling scaffolds.  The authors stated that this work is of substantial importance as it showed how the fabrication of hierarchical biomaterials via surface-enrichment of functional HA nanoparticles in composite polymer stereolithographic structures could impact in-vitro and in-vivo osteogenesis.

Lee and co-workers (2017) 3-D bio-printing is a rapidly emerging technique in the field of tissue engineering to fabricate extremely intricate and complex biomimetic scaffolds in the range of micrometers.  Such customized 3-D printed constructs can be used for the regeneration of complex tissues (e.g., cartilage, nerves, and vessels).  However, the 3-D printing techniques often offer limited control over the resolution and compromised mechanical properties due to short selection of printable inks.  To address these limitations, these researchers combined SLA and electro-spinning techniques to fabricate a novel 3-D biomimetic neural scaffold with a tunable porous structure and embedded aligned fibers.  By employing 2 different types of bio-fabrication methods, these investigators successfully utilized both synthetic and natural materials with varying chemical composition as bioink to enhance biocompatibilities and mechanical properties of the scaffold.  The resulting microfibers composed of polycaprolactone (PCL) polymer and PCL mixed with gelatin were embedded in 3-D printed hydrogel scaffold.  These findings showed that 3-D printed scaffolds with electrospun fibers significantly improved neural stem cell adhesion when compared to those without the fibers.  Furthermore, 3-D scaffolds embedded with aligned fibers showed an enhancement in cell proliferation relative to bare control scaffolds.  More importantly, confocal microscopy images illustrated that the scaffold with PCL/gelatin fibers greatly increased the average neurite length and directed neurite extension of primary cortical neurons along the fiber.  The authors concluded that the findings of this study demonstrated the potential to create unique 3-D neural tissue constructs by combining 3-D bio-printing and electro-spinning techniques.

Channasanon and co-workers (2017) noted that porous oligolactide-hydroxyapatite composite scaffolds were obtained by stereolithographic fabrication.  Gentamicin was then coated on the scaffolds afterwards, to achieve anti-microbial delivery ability to treat bone infection.  The scaffolds examined by stereomicroscope, SEM, and μCT-scan showed a well-ordered pore structure with uniform pore distribution and pore inter-connectivity.  The physical and mechanical properties of the scaffolds were examined.  It was shown that not only porosity but also scaffold structure played a critical role in governing the strength of scaffolds.  A good scaffold design could create proper orientation of pores in a way to strengthen the scaffold structure.  The drug delivery profile of the porous scaffolds was also analyzed using microbiological assay.  The authors concluded that the release rates of gentamicin from the scaffolds showed prolonged drug release at the levels higher than the minimum inhibitory concentrations for S. aureus and E. coli over a 2-week period, indicating a potential of the scaffolds to serve as local antibiotic delivery to prevent bacterial infection.

Aisenbrey and associates (2018) stated that damage to articular cartilage can over time cause degeneration to the tissue surrounding the injury.  To address this problem, scaffolds that prevent degeneration and promote neo-tissue growth are needed.  A new hybrid scaffold that combines a stereolithography-based 3D printed support structure with an injectable and photo-polymerizable hydrogel for delivering cells to treat focal chondral defects is introduced.  In this proof of concept study, the ability to (a) infill the support structure with an injectable hydrogel precursor solution, (b) incorporate cartilage cells during infilling using a degradable hydrogel that promotes neo-tissue deposition, and (c) minimize damage to the surrounding cartilage when the hybrid scaffold is placed in-situ in a focal chondral defect in an osteochondral plug that is cultured under mechanical loading is demonstrated.  The authors concluded that with the ability to independently control the properties of the structure and the injectable hydrogel, this hybrid scaffold approach holds promise for treating chondral defects.

Anderson and colleagues (2018) noted that CAD and CAM technologies can leverage cone beam CT data for production of objects used in surgical and non-surgical endodontics and in educational settings.  These investigators reviewed all current applications of 3D printing in endodontics and speculated upon future directions for research and clinical use within the specialty.  They performed a literature search of PubMed, Ovid and Scopus using the following terms: stereolithography, 3D printing, computer aided rapid prototyping, surgical guide, guided endodontic surgery, guided endodontic access, additive manufacturing, rapid prototyping, auto-transplantation rapid prototyping, CAD, CAM.  Inclusion criteria were articles in the English language documenting endodontic applications of 3D printing.  A total of 51 articles met inclusion criteria and were utilized.  The endodontic literature on 3D printing is generally limited to case reports and pre-clinical studies.  Documented solutions to endodontic challenges include: guided access with pulp canal obliteration, applications in auto-transplantation, pre-surgical planning and educational modelling and accurate location of osteotomy perforation sites.  Acquisition of technical expertise and equipment within endodontic practices present formidable obstacles to widespread deployment within the endodontic specialty.  The authors concluded that as knowledge advances, endodontic postgraduate programs should consider implementing 3D printing into their curriculums.  They stated that future research directions should include clinical outcomes assessments of treatments employing 3D printed objects.

Three-Dimensional (3-D) Printed Cranial Implant

On February 18, 2013, the Food and Drug Administration (FDA) granted Performance Materials (OPM) 510(k) clearance for the OsteoFab Patient Specific Cranial Device (OPSCD).  OsteoFab is OPM’s brand for “additively manufactured (also called 3-D Printing)” medical and implant parts produced from PEKK polymer.

On January 19, 2017, OssDsign AB (Uppsala, Sweden) received FDA 510(k) marketing clearance for its 3-D printed OssDsign Cranial PSI (patient-specific implant).  The customized implant is indicated for non-load-bearing applications to reconstruct cranial defects in adults for whom cranial growth is complete and with an intact dura with or without duraplasty.  The OssDsign Cranial PSI is made from a calcium phosphate-based ceramic material, reinforced by a titanium skeleton.  The implant's inter-connecting tile design purportedly allows fluid movement through the device.

Gilardino and colleagues (2015) stated that cranioplasty can be performed either with gold-standard, autologous bone grafts and osteotomies or alloplastic materials in skeletally mature patients.  Recently, custom computer-generated implants (CCGIs) have gained popularity with surgeons because of potential advantages, which include pre-operatively planned contour, obviated donor-site morbidity, and operative time savings.  A remaining concern is the cost of CCGI production.  These researchers compared the operative time and relative cost of cranioplasties performed with autologous versus CCGI techniques at the authors’ center.  These researchers carried out a review of all autologous and CCGI cranioplasties performed at their institution over the last 7 years.  The following operative variables and associated costs were tabulated: length of operating room, length of ward/intensive care unit (ICU) stay, hardware/implants utilized, and need for transfusion.  Total average cost did not differ statistically between the autologous group (n = 15; $25,797.43) and the CCGI cohort (n = 12; $28,560.58).  Operative time (p = 0.004), need for ICU admission (p < 0.001), and number of complications (p = 0.008) were all statistically significantly less in the CCGI group.  The length of hospital stay (LOS) and number of cases needing transfusion were fewer in the CCGI group but did not reach statistical significance.  The authors concluded that the findings of this study demonstrated no significant increase in overall treatment cost associated with the use of the CCGI cranioplasty technique.  In addition, the latter was associated with a statistically significant decrease in operative time and need for ICU admission when compared with those patients who underwent autologous bone cranioplasty.  Level of Evidence = IV.  The authors stated that this study had drawbacks that forced cautious interpretation of the results.  They stated that a major drawback was that the findings represented a preliminary study, based on an analysis of a small study population.

Choi and Kim (2015) stated that 3-D printing has been widely adopted in medical fields.  Application of the 3-D printing technique has even been extended to bio-cell printing for 3-D tissue/organ development, the creation of scaffolds for tissue engineering, and actual clinical application for various medical parts.  Of various medical fields, craniofacial plastic surgery is one of areas that pioneered the use of the 3-D printing concept.  Rapid prototype technology was introduced in the 1990s to medicine via computer-aided design, computer-aided manufacturing.  These investigators examined the current status of 3-D printing technology and its clinical application; they performed a systematic review of the literature.  In addition, these researchers reviewed the benefits and possibilities of the clinical application of 3-D printing in craniofacial surgery, based on personal experiences with more than 500 craniofacial cases conducted using 3-D printing tactile prototype models.  These investigators stated that 3-D printing technology has the potential to be very beneficial to patients and doctors in terms of patient-specific individualized medicine.

The authors stated that 3-D printing techniques have been most actively used in craniofacial surgery.  However, some obstacles need to be overcome.  First, the computer software used for craniofacial reconstruction should be much more specifically designed.  The pre-operative design of surgery is not especially easy however.  Because the segmentation process in computer simulations is time consuming, it needs to be more automated.  If the various software programs were more suitable and specific for craniofacial reconstruction, the 3-D printing technique could be more actively used.  Second, a connection between the pre-operative simulations and the real surgery environment should be made.  Surgical wafers, such as intermediate and final dental splints, would be an example in orthognathic surgery.  In addition, a navigational system could act as a surgical guide to connect the pre-operative simulation and the actual surgery.  In order to apply the 3-D printed titanium implant, the surgical cut or ostectomy should be matched precisely with the pre-operative planning.  Because the 3-D printed implant is so solid that it is not easy to cut or bend, planning and surgery should be identical and efforts should be made to ensure that the pre-operative planning and intra-operative defect are in agreement.  Thus, a surgical osteotomy guide should be made.  A third issue is accuracy.  Although CT scans were made in very thin slices, the imaging modality could only provide the accumulation of the multiple slices.  Error can inevitably occur between the slices.  In particular, the orbital wall was too thin to be reconstructed by only a 3-D printing technique and a 3-D printed orbit model represents the orbit as vacant fields.

Park and associates (2016) examined the efficacy of custom-made 3-D printed titanium implants for reconstructing skull defects.  From 2013 to 2015, a total of 21 patients (aged 8 to 62 years, mean of  28.6; 11 females and 10 males) with skull defects were treated.  Total disease duration ranged from 6 to 168 months (mean of 33.6 months).  The size of skull defects ranged from 84  × 104 to 154  × 193 mm.  Custom-made implants were manufactured by Medyssey Co, Ltd (Jecheon, South Korea) using 3-D CT data, Mimics software, and an electron beam melting machine.  The team reviewed several different designs and simulated surgery using a 3-D skull model.  During the operation, the implant was fit to the defect without dead space.  Operation times ranged from 85 to 180 mins (mean of 115.7).  Operative sites healed without any complications except for 1 patient who had red swelling with exudation at the skin defect, which was a skin infection and defect at the center of the scalp flap reoccurring since the initial head injury.  This patient underwent re-operation for skin defect revision and replacement of the implant.  A total of 21 patients were followed for 6 to 24 months (mean of 14.1 months).  Subjects were satisfied and had no recurrent wound problems.  Head CT following operation showed good fixation of titanium implants and satisfactory skull-shape symmetry.  For the reconstruction of skull defects, the use of autologous bone grafts has been the treatment of choice.  However, bone use depends on availability, defect size, and donor morbidity.  These investigators noted that as 3-D printing techniques are further advanced, it is becoming possible to manufacture custom-made 3-D titanium implants for skull reconstruction.

Tack and co-workers (2016) noted that 3-D printing has numerous applications and has gained much interest in the medical world.  The constantly improving quality of 3-D printing applications has contributed to their increased use on patients.  These researchers summarized the literature on surgical 3-D printing applications used on patients, with a focus on reported clinical and economic outcomes.  Three major literature databases were screened for case series (more than 3 cases described in the same study) and trials of surgical applications of 3-D printing in humans.  A total of 227 surgical papers were analyzed and summarized using an evidence table.  These investigators described the use of 3-D printing for surgical guides, anatomical models, and custom implants; 3-D printing is used in multiple surgical domains, such as orthopedics, maxillofacial surgery, cranial surgery, and spinal surgery.  In general, the advantages of 3-D printed parts included reduced surgical time, improved medical outcome, and decreased radiation exposure.  The costs of printing and additional scans generally increase the overall cost of the procedure.  The authors concluded that 3-D printing is already well-integrated in medical practice.  Applications vary from anatomical models (mainly for surgical planning) to surgical guides and implants.  The main advantages stated by the authors of the selected papers were reduced surgical time, improved medical outcome, and decreased radiation exposure.  Unfortunately, the subjective character and lack of evidence supporting majority of these advantages did not allow for conclusive statements.  The increased cost of this new technology, and the often limited or unproven advantages, made it questionable whether 3-D printing is cost effective for all patients and applications. 

Francaviglia and colleagues (2017) noted that cranioplasty represents a challenge in neurosurgery.  Its goal is not only plastic reconstruction of the skull but also to restore and preserve cranial function, to improve cerebral hemodynamics, and to provide mechanical protection of the neural structures.  The ideal material for the reconstructive procedures and the surgical timing are still controversial.  Many alloplastic materials are available for performing cranioplasty and among these, titanium still represents a widely proven and accepted choice.  These researchers presented their preliminary experience with a "custom-made" cranioplasty, using electron beam melting (EBM) technology, in a series of 10 patients; EBM is a new sintering method for shaping titanium powder directly in 3-D implants.  To the best of the authors’ knowledge, this was the first report of a skull reconstruction performed by this technique.  In a 1-year follow-up, no post-operative complications had been observed and good clinical and esthetic outcomes were achieved.  The authors concluded that costs higher than those for other types of titanium mesh, a longer production process, and the greater expertise needed for this technique were compensated by the achievement of most complex skull reconstructions with a shorter operative time.

In a systematic review, Diment and associates (2017) evaluated the efficacy and effectiveness of using 3-D printing to develop medical devices across all medical fields.  Data sources included PubMed, Web of Science, OVID, IEEE Xplore and Google Scholar.  A double-blinded review method was used to select all abstracts up to January 2017 that reported on clinical trials of a 3-D printed medical device.  The studies were ranked according to their level of evidence, divided into medical fields based on the International Classification of Diseases chapter divisions and categorized into whether they were used for pre-operative planning, aiding surgery or therapy.  The Downs and Black Quality Index critical appraisal tool was used to assess the quality of reporting, external validity, risk of bias, risk of confounding and power of each study.  Of the 3,084 abstracts screened, 350 studies met the inclusion criteria.  Oral and maxillofacial surgery contained 58.3 % of studies, and 23.7 % covered the musculoskeletal system.  Only 21 studies were randomized controlled trials (RCTs), and all fitted within these 2 fields.  The majority of RCTs were 3-D printed anatomical models for pre-operative planning and guides for aiding surgery.  The main benefits of these devices were decreased surgical operation times and increased surgical accuracy.  The authors concluded that all medical fields that assessed 3-D printed devices concluded that they were clinically effective.  The fields that most rigorously assessed 3-D printed devices were oral and maxillofacial surgery and the musculoskeletal system, both of which concluded that the 3-D printed devices out-performed their conventional comparators.  However, the efficacy and effectiveness of 3-D printed devices remained undetermined for the majority of medical fields.  These investigators stated that this study was limited to a critical appraisal of individual studies, rather than a meta-analysis, because of the breadth of uses (from anatomical models and surgical guides to therapeutic devices) and the lack of comparable hypotheses; they stated that more rigorous and long-term assessments are needed to determine if 3-D printed devices are clinically relevant before they become part of standard clinical practice.

Volpe and co-workers (2018) validated a design methodology for the virtual surgery and the fabrication of cranium vault custom plates.  Recent advances in the field of medical imaging, image processing and additive manufacturing (AM) have led to new insights in several medical applications.  The engineered combination of medical actions and 3-D processing steps, foster the optimization of the intervention in terms of operative time and number of sessions needed.  Complex craniofacial surgical intervention, such as for instance severe hypertelorism accompanied by skull holes, traditionally requires a 1st surgery to correctly "re-size" the patient cranium and a 2nd surgical session to implant a customized 3-D printed prosthesis.  Between the 2 surgical interventions, medical imaging needs to be performed to aid the design the skull plate.  Instead, this paper proposed a CAD/AM-based one-in-all design methodology allowing the surgeons to perform, in a single surgical intervention, both skull correction and implantation.  A strategy envisaging a virtual/mock surgery on a CAD/AM model of the patient cranium so as to plan the surgery and to design the final shape of the cranium plaque is proposed.  The procedure relies on patient imaging, 3-D geometry reconstruction of the defective skull, virtual planning and mock surgery to determine the hypothetical anatomic 3-D model and, finally, to skull plate design and 3-D printing.  The methodology has been tested on a complex case study.  Results demonstrated the feasibility of the proposed approach and a consistent reduction of time and overall cost of the surgery, not to mention the huge benefits on the patient that is subjected to a single surgical operation.  The authors concluded that despite a number of AM-based methodologies have been proposed for designing cranial implants or to correct orbital hypertelorism, to the best of the their knowledge, the present work was the first to simultaneously treat osteotomy and titanium cranium plaque.

Huang and colleagues (2019) examined the biomechanical behaviors of the pre-shaped titanium (PS-Ti) cranial mesh implants with different pore structures and thicknesses as well as the surface characteristics of the 3-D printed Ti (3DP-Ti) cranial mesh implant.  The biomechanical behaviors of the PS-Ti cranial mesh implants with different pore structures (square, circular and triangular) and thicknesses (0.2, 0.6 and 1 mm) were simulated using finite element analysis.  Surface properties of the 3DP-Ti cranial mesh implant were performed by means of scanning electron microscopy, X-ray diffraction and static contact angle goniometer.  It was found that the stress distribution and peak Von Mises stress of the PS-Ti cranial mesh implants significantly decreased at the thickness of 1 mm.  The PS-Ti mesh implant with the circular pore structure created a relatively lower Von Mises stress on the bone defect area as compared to the PS-Ti mesh implant with the triangular pore structure and square pore structure.  Moreover, the spherical-like Ti particle structures were formed on the surface of the 3DP-Ti cranial mesh implant.  The microstructure of the 3DP-Ti mesh implant was composed of α and rutile-TiO2 phases.  For wettability evaluation, the 3DP-Ti cranial mesh implant possessed a good hydrophilicity surface.  The authors concluded that the 3DP-Ti cranial mesh implant with the thickness of 1 mm and circular pore structure is a promising biomaterial for cranioplasty surgery applications.

Penile Surface Mold Brachytherapy

D'Alimonte and colleagues (2019) described a technique of penile surface mold high-dose-rate (HDR) brachytherapy and early outcomes.  A total of 5 patients diagnosed with a T1aN0 squamous cell carcinoma (SCC) of the penis were treated using a penile surface mold HDR brachytherapy technique.  A negative impression of the penis was obtained using dental alginate; CT images were acquired of the penile impression; subsequently, a virtual model of the patient's penis was generated.  The positive model was imported into a computer-assisted design program where catheter paths were planned such that an optimized off-set of 5 mm from the penile surface was achieved.  The virtual model was converted into a custom applicator.  A total dose of 40 Gy was delivered in 10 fractions.  Patients were followed at 1, 3, 6, and 12 months after treatment and then every 6 months thereafter.  Toxicities were reported using Common Terminology Criteria for Adverse Events v4.0.  All patients tolerated treatment well.  Acute grade-2 skin reactions were observed within the 1st month following treatment.  Median follow-up was 35 months.  Late grade-1 skin toxicities were observed; 1 patient experienced a urethral stricture requiring dilatation; and 2 patients developed local recurrence.  The authors concluded that this technique allowed the delivery of penile HDR brachytherapy as an out-patient procedure with minimal discomfort to the patient during each application and was a repeatable and accurate set-up.  These researchers stated that this technique needs validation in larger series with longer follow-up.

3D Printing of Anatomic Structures for Pre-Operative Planning

Vukicevic and colleagues (2017) noted that as catheter-based structural heart interventions become increasingly complex, the ability to effectively model patient-specific valve geometry as well as the potential interaction of an implanted device within that geometry will become increasingly important.  These investigators combined the technologies of high-spatial resolution cardiac imaging, image processing software, and fused multi-material 3D printing, to demonstrate that patient-specific models of the mitral valve apparatus could be created to facilitate functional evaluation of novel trans-catheter mitral valve repair strategies.  Clinical three-dimensional (3D) trans-esophageal echocardiography (TEE) and computed tomography (CT) images were acquired for 3 patients being evaluated for a catheter-based mitral valve repair.  Target anatomies were identified, segmented and reconstructed into 3D patient-specific digital models.  For each patient, the mitral valve apparatus was digitally reconstructed from a single or fused imaging data set.  Using multi-material 3D printing methods, patient-specific anatomic replicas of the mitral valve were created.  3D print materials were selected based on the mechanical testing of elastomeric TangoPlus materials (Stratasys, Eden Prairie, MN) and were compared to freshly harvested porcine leaflet tissue.  The effective bending modulus of healthy porcine MV tissue was significantly less than the bending modulus of TangoPlus (p < 0.01).  All TangoPlus varieties were less stiff than the maximum tensile elastic modulus of mitral valve tissue (3697.2 ± 385.8 kPa anterior leaflet; 2582.1 ± 374.2 kPa posterior leaflet) (p < 0.01).  However, the slopes of the stress-strain toe regions of the mitral valve tissues (532.8 ± 281.9 kPa anterior leaflet; 389.0 ± 156.9 kPa posterior leaflet) were not different than those of the Shore 27, Shore 35, and Shore 27 with Shore 35 blend TangoPlus material (p > 0.95).  These investigators have demonstrated that patient-specific mitral valve models can be reconstructed from multi-modality imaging data-sets and fabricated using the multi-material 3D printing technology and they provided 2 examples to show how catheter-based repair devices could be evaluated within specific patient 3D printed valve geometry.  Moreover, the authors concluded that the use of 3D printed models for the development of new therapies, or for specific procedural training has yet to be defined.

Leng and associates (2017) provided a framework for the development of a quality assurance (QA) program for use in medical 3D printing applications.  An inter-disciplinary QA team was built with expertise from all aspects of 3D printing.  A systematic QA approach was established to examine the accuracy and precision of each step during the 3D printing process, including: image data acquisition, segmentation and processing, and 3D printing and cleaning.  Validation of printed models was performed by qualitative inspection and quantitative measurement.  The latter was achieved by scanning the printed model with a high resolution CT scanner to obtain images of the printed model, which were registered to the original patient images and the distance between them was calculated on a point-by-point basis.  A phantom-based QA process, with 2 QA phantoms, was also developed.  The phantoms went through the same 3D printing process as that of the patient models to generate printed QA models.  Physical measurement, fit tests, and image based measurements were performed to compare the printed 3D model to the original QA phantom, with its known size and shape, providing an end-to-end assessment of errors involved in the complete 3D printing process.  Measured differences between the printed model and the original QA phantom ranged from -0.32 mm to 0.13 mm for the line pair pattern.  For a radial-ulna patient model, the mean distance between the original data-set and the scanned printed model was -0.12 mm (ranging from -0.57 to 0.34 mm), with a standard deviation of 0.17 mm.  The authors concluded that this study described the development of a comprehensive QA program for 3D printing in medicine.  These researchers hoped that the methodologies described would contribute toward the growing body of work needed to establish standards for QA programs for medical 3D printing.

The authors stated that this study had several drawbacks.  First, the protocols were based on experience with a single type of 3D printer and with segmentation software from a single vendor.  The general framework and concepts of this QA program, though, can be extended to other types of printers with appropriate adjustments made according to the specific printing technology and to type of segmentation software.  Second, the authors’ experience relied heavily on the use of CT imaging data that was used for the majority of their models as CT provided high spatial resolution and high geometric accuracy, both of which were critical for 3D printed models used in medicine.  However, general principles outlined in this study applied to 3D printing using other imaging modalities too; MRI data were increasing used as an adjunct to the CT data as higher resolution MRI imaging sequences are being developed.  The use of 3D ultrasound (US) data is still in early stages of exploration for 3D printing.  Finally, the QA program did not provide specific and quantifiable standard for 3D printing.  As this technology evolves, substantial QA data from multiple institutions need to be accumulated over time so that appropriate specific and quantifiable QA standard could be developed and adopted by the medical 3D printing community.

Pucci and co-workers (2017) stated that 3D printers are a developing technology penetrating a variety of markets, including the medical sector.  Since its introduction to the medical field in the late 1980s, 3D printers have constructed a range of devices, such as dentures, hearing aids, and prosthetics.  With the ultimate goals of decreasing healthcare costs and improving patient care and outcomes, neurosurgeons are utilizing this dynamic technology, as well.  Digital Imaging and Communication in Medicine (DICOM) can be translated into stereolithography (STL) files, which are then read and methodically built by 3D printers.  Vessels, tumors, and skulls are just a few of the anatomical structures created in a variety of materials, which enable surgeons to conduct research, educate surgeons in training, and improve pre-operative planning without risk to patients.  Due to the infancy of the field and a wide range of technologies with varying advantages and disadvantages, there is currently no standard 3D printing process for patient care and medical research.  In an effort to enable clinicians to optimize the use of additive manufacturing (AM) technologies, the authors outlined the most suitable 3D printing models and computer-aided design (CAD) software for 3D printing in neurosurgery.  These researchers noted that 3D printing applications and the limitations of 3D printers must be overcome before this technology can significantly impact the field of neurosurgery.

Barber and colleagues (2018) noted that otolaryngologists increasingly use patient-specific 3D-printed anatomic physical models for pre-operative planning.  However, few reports described concomitant use with virtual models.  These investigators employed a 3D-printed patient-specific physical model with lateral skull base navigation for pre-operative planning; reviewed anatomy virtually via augmented reality (AR); and compared physical and virtual models to intra-operative findings in a challenging case of a symptomatic petrous apex cyst; CT imaging was manually segmented to generate 3D models; AR facilitated virtual surgical planning.  Navigation was then coupled to 3D-printed anatomy to simulate surgery using an endoscopic approach.  Intra-operative findings were comparable to simulation.  Virtual and physical models adequately addressed details of endoscopic surgery, including avoidance of critical structures.  The authors concluded that complex lateral skull base cases may be optimized by surgical planning via 3D-printed simulation with navigation.  Moreover, these researchers stated that future studies are needed to examine if simulation could improve patient outcomes, including patient safety.

Lin and associates (2018) noted that using 3D printing to create individualized patient models of the skull base, the optic chiasm and facial nerve can be pre-visualized to help identify and protect these structures during tumor removal surgery.  Pre-operative imaging data for 2 cases of sellar tumor and 1 case of acoustic neuroma were obtained.  Based on these data, the cranial nerves were visualized using 3D T1-weighted turbo field echo sequence and diffusion tensor imaging-based fiber tracking.  Mimics software was used to create 3D reconstructions of the skull base regions surrounding the tumors, and 3D solid models were printed for use in simulation of the basic surgical steps.  The 3D printed personalized skull base tumor solid models contained information regarding the skull, brain tissue, blood vessels, cranial nerves, tumors, and other associated structures.  The sphenoid sinus anatomy, saddle area, and cerebello-pontine angle region could be visually displayed, and the spatial relationship between the tumor and the cranial nerves and important blood vessels was clearly defined.  The models allowed for simulation of the operation, prediction of operative details, and verification of accuracy of cranial nerve reconstruction during the operation.  Questionnaire assessment showed that neurosurgeons highly valued the accuracy and usefulness of these skull base tumor models.  The authors concluded that 3D printed models of skull base tumors and nearby cranial nerves, by allowing for the surgical procedure to be simulated beforehand, facilitated pre-operative planning and may help prevent cranial nerve injury.  Moreover, these investigators noted that although 3D printed models in neurosurgery have been reported, these models lacked some details and practical significance.

Alyaev (2018) developed a non-biological 3D printed simulator for training and pre-operative planning in percutaneous nephrolithotripsy (PCNL), which allowed doctors to master and perform all stages of the operation under US and fluoroscopy guidance.  The 3D model was constructed using multi-slice spiral CT (MSCT) images of a patient with staghorn urolithiasis.  The MSCT data were processed and used to print the model.  The simulator consisted of 2 parts: a non-biological 3D printed soft model of a kidney with reproduced intra-renal vascular and collecting systems; and a printed 3D model of a human body.  Using this 3D printed simulator, PCNL was performed in the interventional radiology operating room under US and fluoroscopy guidance.  The designed 3D printed model of the kidney completely reproduced the individual features of the intra-renal structures of the particular patient.  During the training, all the main stages of PCNL were performed successfully: the puncture, dilation of the nephrostomy tract, endoscopic examination, intra-renal lithotripsy.  The authors concluded that their proprietary 3D-printed simulator was a promising development in the field of endourologic training and pre-operative planning in the treatment of complicated forms of urolithiasis.

Dong and co-workers (2018) reported their experience with customized 3D printed models of patients with brain arterio-venous malformation (bAVM) as an educational and clinical tool for patients, doctors, and surgical residents.  Using CT angiography (CTA) or digital subtraction angiography (DSA) images, the rapid prototyping process was completed with specialized software and "in-house" 3D printing service.  Intra-operative validation of model fidelity was performed by comparing to DSA images of the same patient during the endovascular treatment process; 3D bAVM models were used for pre-operative patient education and consultation, surgical planning, and resident training.  3D printed bAVM models were successfully made.  By neurosurgeons' evaluation, the printed models precisely replicated the actual bAVM structure of the same patients (n = 7, 97 % concordance, range of 95 % to 99 % with average of less than 2 mm variation).  The use of 3D models was associated shorter time for pre-operative patient education and consultation, higher acceptable of the procedure for patients and relatives, shorter time between obtaining intra-operative DSA data and the start of endovascular treatment.  A total of 30 surgical residents from residency programs tested the bAVM models and provided feedback on their resemblance to real bAVM structures and the usefulness of printed solid model as an educational tool.  The authors concluded that further study of 3D printing technology application in neurovascular disease still needs to be performed.  The use of 3D printed models has highest value in aneurysm clipping, pre-operative simulation, and accurate understanding of the local anatomy.  With printed bAVM models, the surgeon could be aware of the structural property of nidus and related vessels, guiding in treatment planning.  However, the models still have some limitations.  Fabrication cost and time varied with model size and the authors’ models did not yet give information regarding detailed structures directly inside the nidus; models that could overcome these limitations are the efforts of these researchers’ ongoing study on human bio-modeling.

Qiu and colleagues (2018) stated that medical errors are a major concern in clinical practice, suggesting the need for advanced surgical aids for pre-operative planning and rehearsal.  Conventionally, CT and MRI scans, as well as 3D visualization techniques, have been used as the primary tools for surgical planning.  While effective, it would be useful if additional aids could be developed and employed in particularly complex procedures involving unusual anatomical abnormalities that could benefit from tangible objects providing spatial sense, anatomical accuracy, and tactile feedback.  Recent advancements in 3D printing technologies have facilitated the creation of patient-specific organ models with the purpose of providing an effective solution for pre-operative planning, rehearsal, and spatiotemporal mapping.  These investigators reviewed the state-of-the-art in 3D printed, patient-specific organ models with an emphasis on 3D printing material systems, integrated functionalities, and their corresponding surgical applications and implications; they also discussed prior limitations, current progress, and future perspectives in this field.

The authors stated that significant advances in 3D printing organ models and their corresponding surgical applications have been achieved.  However, there is still plenty of room for further improvement in the field, and future studies are expected to focus on several different directions.  First, most 3D printed organ models were static, meaning they lacked the ability to simulate dynamic conditions of organ models, such as pulsations of the heart.  Thus, incorporation of convenient and accurate dynamic functionalities (such as actuation) into the organ models will be useful for more realistic surgical rehearsal.  Second, although the initial integration of 3D printed soft electronics has been achieved, the functionalities are still limited.  For more complicated, multi-dimensional feedback applications, different types of conformal electronics with more powerful functionalities need to be developed and integrated into the organ models.  Third, virtual and assisted reality tools could be used in conjunction with the organ models for visualization of fine features such as vasculature during surgical simulation.  Fourth, the 3D printed organ models with integrated functionalities should be evaluated in real-use cases under various surgical environments for statistical surveys of surgical outcomes and patient safety to accurately and quantitatively evaluate their effectiveness with large data assessment criteria.  Finally, anisotropic properties could possibly be introduced into the 3D printed organ models by controlling the orientation of printing pathways and imbedding fillers.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
There are no specific codes for stereolithography:
Other CPT codes related to the CPB:
21076 - 21088	Impression and custom preparation
21100	Application of halo type appliance for maxillofacial fixation, includes removal (separate procedure)
21110	Application of interdental fixation device for conditions other than fracture or dislocation, includes removal
21120 - 21196	Repair, revision, and/or reconstruction bones of face
21206	Osteotomy, maxilla, segmental (e.g., Wassmund or Schuchard)
21210	Graft, bone; nasal, maxillary or malar areas (includes obtaining graft)
21246	Reconstruction of mandible or maxilla, subperiosteal implant; complete
30400 - 30465	Rhinoplasty
42200 - 42225	Palatoplasty
76376	3D rendering with interpretation and reporting of computed tomography, magnetic resonance imaging, ultrasound, or other tomographic modality with image postprocessing under concurrent supervision; not requiring image postprocessing on an independent workstation
76377	requiring image postprocessing on an independent workstation
77316	Brachytherapy isodose plan; simple (calculation[s] made from 1 to 4 sources, or remote afterloading brachytherapy, 1 channel), includes basic dosimetry calculation(s)
77317	intermediate (calculation[s] made from 5 to 10 sources, or remote afterloading brachytherapy, 2-12 channels), includes basic dosimetry calculation(s)
77318	complex (calculation[s] made from over 10 sources, or remote afterloading brachytherapy, over 12 channels), includes basic dosimetry calculation(s)
77767	Remote afterloading high dose rate radionuclide skin surface brachytherapy, includes basic dosimetry, when performed; lesion diameter up to 2.0 cm or 1 channel
77768	lesion diameter over 2.0 cm and 2 or more channels, or multiple lesions
77770	Remote afterloading high dose rate radionuclide interstitial or intracavitary brachytherapy, includes basic dosimetry, when performed; 1 channel
77771	2-12 channels
77772	over 12 channels
77799	Unlisted procedure, clinical brachytherapy
CPT codes not covered for indications listed in the CPB:
0559T	Anatomic model 3D-printed from image data set(s); first individually prepared and processed component of an anatomic structure
+ 0560T	each additional individually prepared and processed component of an anatomic structure (List separately in addition to code for primary procedure)
0561T	Anatomic guide 3D-printed and designed from image data set(s); first anatomic guide
+ 0562T	each additional anatomic guide (List separately in addition to code for primary procedure)
ICD-10 codes not covered for indications listed in the CPB:
Z01.818	Encounter for other preprocedural examination

The above policy is based on the following references: