REVIEW

3D Printing and Personalized Airway Stents

George Z. Cheng . Erik Folch . Adam Wilson . Robert Brik .

Noah Garcia . Raul San Jose Estepar . Jorge Onieva Onieva .

Sidhu Gangadharan . Adnan Majid

Received: February 9, 2016 / Published online: January 16, 2017� The Author(s) 2017. This article is published with open access at Springerlink.com

ABSTRACT

In recent years, the 3D printing industry hasundergone rapid development. Clinicians andresearchers have begun to apply this technologyin procedural planning, tissue engineering, anddevice manufacturing. Rapid prototyping andadditive manufacturing techniques in thehealthcare field have already yielded veryexciting results and point to a bright futureinvolving these technologies. This is especiallytrue in pulmonology. 3D printing industry

growth is accompanied by increasedavailability of 3D printers andprintable materials, which offers excitingarrays of possible applications. In this review,we present a brief history of 3D printing and itsapplications in the medical field with a focus onpulmonology. Additionally, we describe amethodology on how to 3D model and printpersonalized airway prosthesis via 3D Slicer anda commercial 3D printer. We hope this will helpto stimulate additional innovation andapplication of 3D printing in medicine.

Keywords: 3D printing; 3D slicer; Pulmonary;Stent

INTRODUCTION

Airway malformations due to stenosis, malacia,traumatic injury, or external compression fromcancers of the mediastinum can lead tosignificant dyspnea, increased work ofbreathing, decreased exertional tolerance.Current methodologies to address the airwaymalformation are limited to airway stents basedon silicone, metal, or hybrid material. Thesestents are often plagued by a variety of issuesincluding but not limited to the high cost ofmanufacturing, difficulty to place, frequentlymigrating in the airway, and often becoming

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G. Z. Cheng (&)Division of Pulmonary, Allergy, and Critical Care,Duke University Hospital, Duke University MedicalSchool, Durham, NC, USAe-mail: george.cheng@duke.edu

E. FolchDivision of Pulmonary and Critical Care Medicine,Massachusetts General Hospital, Harvard MedicalSchool, Boston, MA, USA

A. Wilson � R. Brik � N. Garcia � S. Gangadharan �A. MajidDivision of Thoracic Surgery and InterventionalPulmonology, Beth Israel Deaconess MedicalCenter, Harvard Medical School, Boston, MA, USA

R. S. J. Estepar � J. O. OnievaDepartment of Radiology, Brigham and Women’sHospital, Harvard Medical School, Boston, MA, USA

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DOI 10.1007/s41030-016-0026-y

obstructed by granulation tissues. Developmentof novel approach to manufacture airway stentsis urgently needed to address these issues [1].

Many consider 3D printing the thirdindustrial revolution [2]. Unlike conventionalmanufacturing, 3D printing technology allowsadditive manufacturing, which results in lessraw material waste, decreased cost ofmanufacturing, and increased freedom ofdesign. The ability to alter rapidly and testnew designs is often referred to as rapidprototyping. This freedom for customizingcomplex designs makes 3D printing anespecially appealing technology to the field ofmedicine. 3D printing has been increasinglyapplied to medical disciplines wheretherapeutic interventions rely on definingcomplex anatomic structural relationships [3].This article aims to provide a brief history of 3Dprinting development and medical applicationsin pulmonary medicine. Most importantly, wewill focus on designing personalized airwaystents and review the limitations that the fieldfaces today. This article is based on previouslyconducted studies and does not involve anynew studies of human or animal subjectsperformed by any of the authors.

HISTORY OF 3D PRINTING

Conceptually, 3D printing converts a digital fileinto a physical model. Taking a 3Dcomputer-aided design (CAD) model, printingsoftware performs a virtual slice to create a stackof 2D slices that will then be fed to a 3D printer.The 3D printer will build the 3D object layer bylayer using the 2D slices by joining these layerstogether. 3D printing has its origins in the1980s. Charles ‘‘Chuck’’ Hull, co-founder of 3DSystems, is credited with the invention of theworld’s first 3D printer (stereolithography, SLA)in 1983. SLA (3D systems INC, Rock Hill, SC,USA; Formlabs, Somerville, MA, USA) uses anultraviolet laser light to trace at the surface of apool of photosensitive resin, where the lasercomes into contact with resin there is a localpolymerization and crosslinking of the liquidresin [2]. The reaction platform israised/dropped as each layer of the 2D

cross-section is created. This method offershighly accurate models, but is limited by theavailable photopolymer resin for use [4]. In themid to late 1980s, there was a proliferation of3D printing technology. In 1987, Dr. CarlDeckard, as a graduate student at theUniversity of Texas Austin, developed theselective laser sintering (SLS) process. Selectivelaser sintering (3D systems INC, Rock Hill, SC)uses a carbon dioxide laser to fuse thermoplasticpowder ranging from plastic, metal, to ceramic.After sintering a cross-section, the powderplatform descends 1 layer thickness and a newlayer of thermoplastic powder is applied. Thismethod increases the range of materials, affordshigh accuracy and resolution, but at a highercost. In 1989, Scott Crump invented fusiondeposition modeling (FDM) and went on toco-found Stratasys Inc. FDM (Stratasys Inc, EdenPrairie, MN, USA) extrudes various filaments orplastic pellets, most commonly acyrylonitrilebutadiene styrene (ABS) and polylactic acid(PLA), through a heated extrusion nozzle. Theprinter nozzle moves in an x–y–z plane andtraces each cross-sectional layer that hardensafter extrusion on a platform. FDM offers highgeometric accuracy and resolution with a widerange of material. Today, these two companies,3D systems and stratasys, are the leaders in the3D printing industry [2]. In 1993, EmanuelSachs of Massachusetts Institute of Technologydeveloped three-dimensional printing (3DP)that applies a thin layer of powder substrateon a build platform, then solidifies each layerswith a liquid binder that enable rapid prototypemodeling. The process allows a range ofmaterial, but does not produce functional finalparts.

For the first two decades of its existence, 3Dprinting was limited to industrial purposes,which was expensive and proprietary. Theintroduction of 3D printing to the everydayconsumer began through open source projectslike RepRap (lead by Dr. Adrian Bowyer ofUniversity of Bath) and FAB@Home (lead byDr. Hod Lipson of Cornell University). Thesedo-it-yourself (DIY) projects coincided withseveral patent expirations that allowed thedevelopment of affordable desktop 3D printersystems and led to the rise of the entry-level 3D

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printer industry. The adoption by both privateand public sectors has resulted in rapid growthof the 3D printing industry, currently valued atfive billion dollars and projected to grow to over20 billion dollars worldwide in 2020 (Fig. 1) [5].

3D PRINTING AND MEDICALAPPLICATIONS

Since 1990, 3D printing has been used in oraland maxillofacial surgery [6], neurosurgery [7],and orthopedics [8]. Investigators usedcomputerized tomography (CT) and magneticresonance imaging (MRI) data to createanatomical models of long bones, facial bones,brain, heart, and lung. These applications of 3Dprinting have proved to be valuable inpreoperative planning, education and training,intraoperative use of instruments, and evenimplantable devices [4, 9]. Perhaps the mostexciting potential of the technology is theefforts in creating biological scaffolds forreseeding, which lays the foundation for thedevelopment of organ printing in the future[10–12].

AIRWAY STENTS CONSIDERATIONS

The tracheobronchial tree is well suited for 3Dprinting [13]. Human adult trachea spans 10–13centimeters (cm), with 16–20 c-shapedcartilages anteriolaterally, while the posteriortrachea is membranous. The right and leftmainstem bronchus is *1.5 and 4–4.5 cm inlength, respectively. Internal diameter for thetrachea, right and left mainstem bronchi are16–20, 10–12, and 8–12 mm, respectively [14].The silicone stents (Dumon stents, Novatech)

have a range of diameter (9–18 mm), thickness(1–1.5 mm), and length (20–110 mm). Thesestents are manufactured via conventional moldinjection techniques. While customization ispossible, the custom stent requires significanttime and cost due to the need to create a newmold for each change in design [15]. Thisrepresents an opportunity to apply 3Dprinting technology to the manufacturing ofairway stents.

CURRENT DEVELOPMENTSIN PULMONOLOGY

Recently, several different groups reporteddifferent approaches of applying 3D printingto address clinical problems in pulmonology.Morrison et al. created personalized airwaysplints for pediatric patients withtracheobronchomalacia using MATLAB(MathWorks) and Mimics (Materialise, NV,USA) based on CT data. The airway splint wasprinted via Formiga P 100 System (EOSe-Manufacturing Solutions, Munich, Germany)with a blend of 96% CAPA 6501 PCL(Polysciences Inc, Warrington, PA, USA) and4% hydroxyapatitie (Plasma Biotal Ltd.,Derbyshire, UK). Subsequently, the splintswere treated with air blasting, sonication in70% ethanol for 30 min, and ethylene oxidesterilization at 49 �C. The airway splints wereimplanted under the medical device emergencyuse exemption. All patients responded totreatment as expected [16]. There have beenincreasingly more case reports using 3D printedmodels in thoracic surgery planning or stentplacement. Tam et al. 3D printed an airwaymodel using a CT scan from a patient withtracheobronchial chondromalacia to

Fig. 1 Brief historictimeline of 3D print-ing development

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understand and characterize better the extentand location of stenosis or malacic changes.Kurenov et al. showed that it is readily feasibleto 3D print pulmonary arteries from CT data,allowing for surgical planning. Finally, ourgroup has recently reported using 3D customdesigned t-tube, for a patient with recurrentmedullary thyroid cancer status post resection,to bridge a segment of trachea that is fashionedfrom AlloDerm (LifeCell, Branchburg, NJ, USA)[13, 17, 18]. These articles, when taken together,suggest that personalized airway prosthesis via3D design and printing is a feasible approach.

AIRWAY MODELING

Our group has examined several softwarepackages to aid in 3D modeling and design. Inour experience, 3D Slicer (a free, open sourcesoftware) offers a user-friendly approach tomedical visualization and computation (www.slicer.org). Initially started as a collaborativeproject from MIT and surgical planning lab(SPL), the 3D Slicer prototype was built by DavidGering in 1999, further developed by StevePieper and Ron Kikinis under the support ofNational Institutes of Health (NIH) [19].

3D Slicer provides an extensible platform formany automated algorithms. Nardelli et al.developed an airway segmentation algorithmas a 3D Slicer extension and validated theirapproach with different of CT scan parameters.Applying a region-growing approach, using aseed voxel and a threshold for separating airfrom tissue, the author generated a veryaccurate tracheobronchial tree [20]. Theprocess to generate a physical airway model isstraightforward when using this extension.(video 1).

After opening 3D Slicer, the user will need toinstall the airway segmentation module. Afterloading the CT scan, airway segmentationmodule can be applied to the dataset. Withinthe airway segmentation extension, fiducials (orseeds) are placed in the trachea, right and leftbronchi, respectively. Airway modeling canbegin after placement of the fiducials. Aftergenerating digital airway model, the user cansave the model into .STL format, which is a

printable file in a 3D printer. The physicalmodel can be generated from a 3D printer.(Fig. 2).

AIRWAY INSPECTOR

Using the airway inspector extension (www.airwayinspector.org), 3D Slicer has been used toperform CT-based quantification of COPDpatients by extracting lung densitometry anal-ysis such as air trapping quantification. Using3D Slicer, COPDGene investigators evaluatedover 3600 subjects’ CT scans and found thatairway wall thickness increased with bron-chodilator responsiveness [21–25]. In a recentstudy of patients with NSCLC, Velazquez et al.extracted volumetric data on NSCLC size using3D Slicer extensions [26]. The ability to provideaccurate tumor growth assessment allows moreprecise treatment response monitoring. Theseapproaches illustrate how 3D slicer is appliedtoday and hints at the exciting potential incomputational medical imaging.

COMBINING ART, ENGINEERING,AND MEDICINE

3D model of the airway can be easily done with3D Slicer or an equivalent imaging software.The airway model can be further modified incommercially available digital modelingsoftware, such as SolidWorks (DS SolidWorksCorp. Waltham, MA, USA) or Rhino(Rhinoceros; Robert McNeel & Associates,Seattle, WA, USA). Using SolidWorks, thephysician can accurately design airwayprosthesis based on anatomical boundaries.These designs can be rapidly altered to matchclinical needs. A 3D printer can print the airwayprosthesis model into a physical model for rapidprototyping. Using Rhino, the designers cancreate repeated patterns via a process known astessellation. This process uses the virtualboundary from the airway walls as the surfacewhere multiple patterns can be repeated. Theseprocesses can be used to generate a variety ofstents in a matter of hours. Collaborating withengineers, the physical 3D printed model can be

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converted into silicone stent via injectionmolding. However, the most reliable andreproducible way to create silicone stent is todo indirect 3D printing (i.e. using the digitalmodel of the airway to generate a digital moldfor casting, which is then 3D printed). Thesilicone stent can then be manufactured (Fig. 3).

Perhaps more exciting, the next generationairway inspector is being developed. The chestimaging platform (www.chestimagingplatform.org) aims to facilitate chest CT imaging com-putational analysis. When complete, CIP willprovide physicians with a portfolio of analytictools for CT imaging analysis that includes lungdensity, airway wall thickness, airway size, vas-cular distribution, and vascular size. Addition-ally, using the information gathered, one mayperform disease-specific quantification taskssuch as digital modeling of airway, automaticsizing of stents, and even guidance of stentplacement (Fig. 4) [27].

BARRIERS IN 3D MEDICALPRINTING

Despite the exciting developments inhealthcare 3D printing, we are faced withseveral challenges. While 3Dprintable materials are increasing, there is stilla lack of FDA approved, 3D printable, flexible,implantable grade material that is suited formanufacturing endobronchial stents.Furthermore, the lack of clear FDA guidanceon cleansing and material testing protocols for3D printed products makes it hard for designersand manufacturers. Four sterilizationtechniques are commonly used to sterilizemedical equipment. Autoclaves with steam athigh temperature (121 or 132 �C ) and pressureis commonly used for equipment cleansing;however, most materials from 3D printerscannot tolerate these conditions. Low

Fig. 2 a Personalizedstent project workflowschematic. b 3D slicerguided stent designand rapid prototyping

Fig. 3 a Tessellatedstents. b Current andcustom silicone stent

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temperature ([60 �C ) approaches, such asethylene oxide, hydrogen peroxide, andgamma radiation, are more suitable forsterilize 3D printed material [28]. Typically,several FDA pathways can bring a product tomarket. Premarket approval (PMA), 510(k), andhumanitarian use device (HUD) are the mostcommon [29]. Medical devices are classified intoclass I, II, and III, with increasing risk associatedwith higher the class, which require a veryrigorous evaluation process [30].510(k) approval requires a new product todemonstrate equivalence to a prior marketeddevice, which requires a less stringent reviewprocess [31]. Humanitarian use device (HUD)pertains to devices targeting rare disease (\4000patients per year) that can get to marketwithout effectiveness guarantee [32].Currently, the majority of 3D printed devicesreceived FDA approval via 510(k) [33, 34].Similarly, the European commission also hasregulatory framework for medical devices,which falls under council directive 90/385/EEC, 93/42/EEC, and 98/79/EEC that applies toactive implantable medical devices (AIMDD),medical devices (MDD), and in vitro diagnosticmedical devices (IVDMD), respectively. 3Dprinted devices that are implantable and based

on morphological features specific of eachpatient are classified as custom-made devicesaccording to the directive 93/42/EEC.

EXCITING FUTURE DIRECTIONS

As the field of 3D printing expands intohealthcare, it is only a matter of time topersonalized medical devices that can bemanufactured onsite (i.e. in the hospital). Thisdevelopment will bring customization ofmedical prosthesis to address each patient’sspecific needs. Airway stents are a perfectexample. Given individual anatomy and needsdiffer (i.e. central airway stenosis withanatomical distortion), airway stents should bemanufactured with those personalized criteriain mind. Currently, airway prosthesis such asairway stents is mass-produced withoutsignificant consideration to the individualairway parameters. This often results in stentmigration due to poor sizing and fit of the stent.Additionally, granulation tissue formation canoccur at the end of the stents due to constantmechanical irritation resulting from a stentdigging into the airway tissue. Theselimitations of the current airway stents can be

Fig. 4 3D Slicer stentmodeling as part ofthe CIP package forstent modeling. Stentmodel is based on CTdataset. The coronal,sagittal, axial views ofCT scan and modelstent based on the 3Dreconstruction of theairway are presented

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reduced with a 3D printed personalized airwaystent that is a perfect match to the patient’sairway. While this is an exciting possibility, thefull potential of 3D printed airway stentsremains to be evaluated through futureclinical trials. Current limitation for therealization of 3D printed airway stent is thelack of a suitable 3D printable flexible,biocompatible material. However, with theexpansion of 3D printing involve drug-eluting,biodegradable stents or grafts, which are alreadybeing explored in the cardiovascular arena, weare hopeful that a suitable material will beavailable in the near future [35]. Personalizedairway prosthesis will be a reality in theforeseeable future.

ACKNOWLEDGMENTS

CIMIT/NIH fundingwasused for 3DmodelingandCIP development. No funding or sponsorship wasreceived for publication of this article.All named authors meet the International

Committee of Medical Journal Editors (ICMJE)criteria for authorship for this manuscript, takeresponsibility for the integrity of the work as awhole, and have given final approval for theversion to be published.

Disclosures. George Z Cheng, Erik Folch,Adam Wilson, Robert Brik, Noah Garcia, RaulSan Jose Estepar, Jorge Onieva Onieva, SidhuGangadharan, and Adnan Majid have nothingto disclose.

Compliance with Ethics Guidelines. Thisarticle is based on previously conducted studiesand does not involve any new studies of human oranimal subjects performed by any of the authors.

Open Access. This article is distributedunder the terms of the Creative CommonsAttribution-NonCommercial 4.0 InternationalLicense (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercialuse, distribution, and reproduction in anymedium, provided you give appropriate credit tothe original author(s) and the source, provide a

link to the Creative Commons license, andindicate if changes were made.

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