The Promise and Challenges of 3D Bioprinting in Otolaryngology: A Contemporary Perspective Viewpoint.

The Promise and Challenges of 3D Bioprinting in Otolaryngology: A Contemporary Perspective Viewpoint. | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL Clinical Otolaryngology This is a preprint and has not been peer reviewed. Data may be preliminary. 28 April 2025 V1 Latest version Share on The Promise and Challenges of 3D Bioprinting in Otolaryngology: A Contemporary Perspective Viewpoint. Authors : Alfio Torrisi 0000-0003-2404-5062 , Mario Lentini , Salvatore Pezzino , Caterina Gagliano 0000-0001-8424-0068 , Salvatore Lavalle , Jerome Rene Lechien , Roberta Malaguarnera , Sergio Castorina , Filippo Torrisi , and A. Maniaci [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174582249.96179914/v1 Published Clinical Otolaryngology Version of record Peer review timeline 350 views 191 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Objectives: To conduct a critical review of the current applications, challenges, and future directions of three-dimensional bioprinting (3DBP) in otolaryngology with a focus on surgical education, personalized implants, and regenerative medicine. Design: Expert opinion based on a targeted literature review and clinical experience. Setting: Translational research relevance of academic otolaryngology. Main Outcome Measures: Assessment of bioprinting approaches and new materials, anatomical accuracy, overcoming limitations by pairing with enhanced technology as virtual and augmented reality, Results: 3DBP is fast becoming an asset to otolaryngology. These Stereolithography (SLA) models facilitate the use of high-fidelity temporal bone models for surgical simulation and training. Functional outcomes of patient-specific implants for ossiculoplasty and cochlear implantation are promising, albeit mostly in preclinical settings. Educators have turned to virtual and augmented reality platforms to improve classroom experiences. But significant hurdles remain, including biocompatibility, the cost of high-resolution technologies, and regulatory impediments to clinical translation. Conclusion: Numerous studies have reported on the transformative potential of 3DBP for surgical planning, education, and implementation of personalized treatment in otolaryngology. A balanced assessment of both its current limitations and future promise is essential for ethical integration. The translation of this technology into routine practice will require multidisciplinary collaboration and rigorous validation through clinical trials. The Promise and Challenges of 3D Bioprinting in Otolaryngology: A Contemporary Perspective Viewpoint. Objectives: To conduct a critical review of the current applications, challenges, and future directions of three-dimensional bioprinting (3DBP) in otolaryngology with a focus on surgical education, personalized implants, and regenerative medicine. Design: Expert opinion based on a targeted literature review and clinical experience. Setting: Translational research relevance of academic otolaryngology. Main Outcome Measures: Assessment of bioprinting approaches and new materials, anatomical accuracy, overcoming limitations by pairing with enhanced technology as virtual and augmented reality, Results: 3DBP is fast becoming an asset to otolaryngology. These Stereolithography (SLA) models facilitate the use of high-fidelity temporal bone models for surgical simulation and training. Functional outcomes of patient-specific implants for ossiculoplasty and cochlear implantation are promising, albeit mostly in preclinical settings. Educators have turned to virtual and augmented reality platforms to improve classroom experiences. But significant hurdles remain, including biocompatibility, the cost of high-resolution technologies, and regulatory impediments to clinical translation. Conclusion: Numerous studies have reported on the transformative potential of 3DBP for surgical planning, education, and implementation of personalized treatment in otolaryngology. A balanced assessment of both its current limitations and future promise is essential for ethical integration. The translation of this technology into routine practice will require multidisciplinary collaboration and rigorous validation through clinical trials. Keywords: 3D bioprinting, biomaterials, otolaryngology, tissue engineering, regenerative medicine, personalized medicine, surgical planning. Level of Evidence: V Bullet points • 3D bioprinting of high-fidelity anatomical models improves surgical teaching and preoperative planning in complex otologic surgery, while stereolithography can recreate the temporal bone down to the millimetre. • While still in its early stages, the use of patient-specific implants for ossicular chain reconstruction and cochlear implantation is a potential area for enhanced outcomes for patients with conductive hearing loss through tailored treatments. • The integration of 3D bioprinted models with virtual/augmented reality platforms can provide immersive learning environments that likely speed the acquisition of surgical skills and improve intuitive comprehension of complex anatomical relationships. • Significant barriers to widespread clinical implementation exist, including concerns about biocompatibility and long-term stability of implantable constructs, significant economic challenges for high-resolution technologies, and regulatory hurdles. • The establishment of standardized bioprinting protocols and corresponding validation pathways will necessitate multi-centre collaboration of otolaryngologists to enable bioengineers and material scientists to provide the evidence base for clinical translation. Introduction Otolaryngology poses a unique challenge due to the complexity and compactness of head and neck anatomy for surgical practice and education. In challenging anatomical areas, such as the temporal bone, middle ear, and skull base, this spatial understanding and surgical skill development is often insufficiently represented in traditional training models and imaging-based preoperative planning. The 3DBP, an additive manufacturing technique, has the potential to revolutionize the generation of patient specific, high-fidelity anatomical models and implantable constructs. These models enable procedural simulation, surgical training, and even tissue regeneration. In otologic surgery, stereolithographic models have been used to improve mastoidectomy training and have shown sub-millimetre accuracy in replicating the ossicular chain [1,2]. Individualized 3D-printed prostheses have been used successfully in ossiculoplasty and cochlear implantation, and both functional and anatomical comparability to native structures has been shown [3-5]. However, other grafts and hydrogel-based scaffolds are still being investigated for tympanic membrane repair and bone regeneration suggesting an inevitable paradigm shift in reconstructive otologic care [6-9]. Undeniably, important limitations remain despite these advances. These elements hinder its routine clinical application due to limitations in biocompatibility, resolution, regulatory, and cost issues [10,11]. Moreover, although virtual and augmented reality integrations of various 3D models have been demonstrated, especially improving surgical education [12,13], their general usability has yet to be established. This viewpoint seeks to summarize current 3DBP applications in otolaryngology, highlight exciting areas of promise, and discuss challenges that need to be overcome for safe and effective clinical integration. Methods Design This manuscript is a narrative Viewpoint article using a targeted literature search, supplemented by clinical experience. The goal of this review was to examine the current and potential clinical applications of 3DBP in the field of otolaryngology, specifically focusing on its use in surgical education, patient-specific implants, and tissue engineering. Setting An academic otolaryngology and translational research environment were used for this review, which illustrates the interdisciplinary relationship between surgical subspecialists and biomedical engineers. Participants There was no human subject participants involved directly. This study is a constituent part of a systematic review based on an analysis of previously published studies and does not report original patient data or interventions. Main Outcome Measures The co-primary outcomes of interest were: • Overall influence of 3D bio-printing in otolaryngologic clinical practice • Accuracy and verification of anatomical models • Application of 3DBP in surgical preparation and teaching • Implications for regenerative medicine and implantable constructs Ethical Considerations No human participants, identifiable data nor interventions were involved in this study. No institutional review board (IRB) or ethical approval was needed. The review was derived entirely from publicly available, already-published data. Reporting Guideline Preparation of this manuscript was guided by PRISMA-ScR (the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) and the COA guidelines for literature-based Viewpoint articles. Results 3D Bioprinting in Surgical Education 3D bioprinting has revolutionized surgical training in otolaryngology by allowing for the development of inexpensive, anatomically correct models. SLA has been used to create high-fidelity temporal bone models suited for mastoidectomy and middle cranial fossa simulations [1,14]. Comparable tactile and spatial nature of feedback is offered by way of these models [19], which can be utilized, along with traditional dissection techniques, to further develop procedural preparedness (Table I) Freiser et al. demonstrated the educational benefits of consumer-grade SLA models with sub-millimetre resolution [1]. Custom 3D-printed simulators have also helped middle ear training. Models for ossiculoplasty [15], stapedotomy [16], and tympanic membrane repair [6,7] enhance procedural preparation and spatial comprehension. More sophisticated designs, including embedding the facial and cochlear nerve pathways, deliver near-clinical fidelity [17](Fig. 1). Bioprinted models, when combined with virtual and augmented reality (VR/AR) environments, improved learning methods with surprising positive outcomes. Frendø et al. Cochlear implantation training enhanced with VR simulation adhered to printed models [12]. Applications on digital anatomy platforms and holographic interfaces have emerged in parallel [11,13]. Patient-Specific Guides and Implants One of the main clinical applications of 3D bioprinting is with custom implants. In cadaveric studies, SLA-produced patient-specific ossicular prostheses using UV-cured resins exhibited similar mechanical properties to native ossicles [3,4]. Markodimitraki et al. validated patient-specific cochlear implant templates that increased surgeon accuracy [5]. Based on this data, Della Volpe et al. reported on transcutaneous Bonebridge implant placement guided by individualized 3D skull models and its impact on air-bone gap closure in patients with severe atresia [18]. Similarly, patient adjusted models have been utilized to orient safe surgical corridors in the context of pediatric cochlear surgery [14]. Both methods minimize complications and make anatomic placement easier. Regenerative Engineering and Emerging Biomaterials Bioprinting is finding use also in regenerative applications via scaffold-based tissue engineering. De Angelis et al. showed the efficacy of poly(ε-caprolactone)-based composites in bone regeneration [8], whereas Shehzad et al. devised dual-crosslinked gelatin-based hydrogels with 90% cell viability, a good candidate for otologic scaffolds [9]. Freeman et al. published on positionally controlled release of growth factors from bioactive constructs for directed tissue repair [14]. Multi-material constructs, as shown by Rienas et al., allow for simultaneous modeling of both soft and hard- tissue in a single framework [19]. Collagen, GelMA, and tricalcium phosphate are among the materials yet to be tested for tympanic membrane and ossicular replacement [20-22]. Clinical applications are in ealry stages, yet advances in material science, as described by Lan et al. and Li et al. suggest wider potential for auricular and vocal fold reconstruction [22,23]. In addition, pioneering studies from Murphy, Kang, and Gungor-Ozkerim remain fundamental for the field’s progression toward biologically functional implants [10,20,24]. Discussion The 3DBP is quickly converting from an experimental modality to a clinic-ready platform otolaryngology. This review serves to confirm its multifaceted applications in surgical simulation, tailored surgery and regenerative applications in early studies. 3DBP differs from traditional 3D printing because of its ability to integrate living cells, bioactive molecules and customized biomaterials within clinically significant constructs [20,24]. Strengths and Limitations One of the most significant areas of 3DBP application in otolaryngology is teaching, in particular enhanced surgical teaching. SLA-printed temporal bones and middle ear models are useful adjuncts for skill acquisition in cadaveric and simulation studies [1,14,15,17]. But it won’t take over anytime soon. Preclinical or in vitro models are common, with only a few exceptions [6-8]. Although functional validation has been reported for ossicular prostheses [3] and surgical guides [4,5], there are few high-quality, longitudinal data of clinical outcomes. Another significant limitation pertains to standardisation. Across studies, the technologies differ in resolution, materials and validation methods, making it challenging to compare across studies. This heterogeneity underlines the necessity for common performance standards and standardized manufacturing routes. Many of the reported designs remain unresolved by respect to biocompatibility, and reproducibility [9-11]. Comparisons to Existing Work In contrast to previous reviews that abstracted across surgical disciplines, this article highlights otolaryngology-specific innovations, including seminal research on cochlear implant guides [5], ossiculoplasty models [15,16], and temporal bone simulation [1,19]. ENT applications are still at a earlier stage of translation than those seen in dental and orthopedic specialties. Still, multi-material strategies like the one discussed in Rienas et al. and Freeman et al. indicates that the field of otolaryngology is starting to integrate more advanced tissue modeling approaches [14,19]. Clinical Applicability and Generalisability Training models are instantly transferrable between teaching centers. Their cost-effective and repeatable nature lends itself well to resident education and preoperative planning. In contrast, with their limited generalisability to routine interventions, patient-specific implants are better suited to complex, anatomically variable cases today, such as paediatric cochlear implantation or congenital atresia [13,18,19]. Regenerative medicine applications as vocal folds or auricular reconstruction are promising but require scalable production methods and clinical-grade validation [22,23]. The bioprinted scaffolds produced by De Angelis and Shehzad are an important first step toward this [8,9]. Conclusions Three-dimensional bioprinting has transformative potential in otolaryngology, enabling advances from high-fidelity anatomical models for surgical training to personalized implants and regenerative solutions. It complements immersive technologies like virtual and augmented reality for enhanced educational engagement and spatial awareness. However, clinical translation is hindered by issues related to biocompatibility, cost, manufacturing resolution and regulatory oversight. As this field continues to grow, we need to have a balanced approach — one that encourages evolution but perhaps with a dose of realism in terms of what is possible right now. Advancements will rely on continued cross-disciplinary cooperation between otolaryngologists, bioengineers, and material scientists. Future work is needed to formulate standard protocols that validate outcomes through clinical studies while introducing 3DBP into routine care practices in a responsible manner that will maximize surgical precision and patient outcomes. This viewpoint seeks to summarize current 3DBP applications in otolaryngology, highlight exciting areas of promise, and discuss challenges that need to be overcome for safe and effective clinical integration. References 1. Freiser M.E., Ghodadra A., McCall A.A., et al. (2021) Operable, Low-Cost, High-Resolution, Patient-Specific 3D Printed Temporal Bones for Surgical Simulation and Evaluation. Ann Otol Rhinol Laryngol 130, 1044–1051. 2. Zhao D., Lu Q., Zou S., et al. (2021) Accuracy of individualized 3D modeling of ossicles using high-resolution computed tomography imaging data. Quant Imaging Med Surg 11, 2406–2414. 3. Sokołowski J., Orłowski A., Lachowska M., et al. (2023) 3D-printed custom ossicular prosthesis - methodology of design and LDV measurements in a cadaver study. Otolaryngol Pol 77, 1–5. 4. Sokołowski J., Orłowski A., Bartoszewicz R., et al. (2024) Quantitative analysis of 3D-printed custom ossicular prostheses motion using laser Doppler vibrometry. Otolaryngol Pol 77, 23–30. 5. Markodimitraki L.M., Ten Harkel T.C., Bleys R.L.A.W., et al. (2022) Cochlear implant positioning and fixation using 3D-printed patient-specific surgical guides; a cadaveric study. PLoS One 17, e0270517. 6. Kuo C.-Y., Wilson E., Fuson A., et al. (2018) Repair of Tympanic Membrane Perforations with Customized Bioprinted Ear Grafts Using Chinchilla Models. Tissue Eng Part A 24, 527–535. 7. Kozin E.D., Black N.L., Cheng J.T., et al. (2016) Design, fabrication, and in vitro testing of novel three-dimensionally printed tympanic membrane grafts. Hear Res 340, 191–203. 8. De Angelis N., Amaroli A., Lagazzo A., et al. (2023) Poly(ε-caprolactone) scaffolds for bone regeneration. Biology (Basel) 12, 1474. 9. Shehzad A., Mukasheva F., Moazzam M., et al. (2023) Dual-Crosslinking of Gelatin-Based Hydrogels: Promising Compositions for a 3D Printed Organotypic Bone Model. Bioengineering 10, 704. 10. Kang H.-W., Lee S.J., Ko I.K., et al. (2016) A 3D bioprinting system to produce human-scale tissue constructs. Nat Biotechnol 34, 312–319. 11. Zhong N. & Zhao X. (2017) 3D printing for clinical application in otorhinolaryngology. Eur Arch Otorhinolaryngol 274, 4079–4089. 12. Frendø M., Frithioff A., Konge L., et al. (2021) Cochlear implant surgery: Learning curve in virtual reality simulation training and transfer of skills to a 3D-printed temporal bone - A prospective trial. Cochlear Implants Int 22, 330–337. 13. Frendo M., Bartoli A. & Calvo J. (2021) VR and 3D printed model integration in CI training. Cochlear Implants Int 22, 330–337. 14. Freeman F.E., Pitacco P., van Dommelen L.H.A., et al. (2020) Spatiotemporally defined growth factor release in bioprinted scaffolds. Sci Adv 6, eabb5093. 15. Lähde S., Hirsi Y., Salmi M., et al. (2024) Integration of 3D-printed middle ear models and middle ear prostheses in otosurgical training. BMC Med Educ 24, 451. 16. Razavi C., Galaiya D., Vafaee S., et al. (2021) Low-cost middle-ear training model for surgical management of otosclerosis. Laryngoscope Investig Otolaryngol 6, 1133–1136. 17. de Souza M.A., Bento R.F. & Lopes P.T. (2023) A 3D printed otological model for cholesteatoma mastoidectomy training. Eur Arch Otorhinolaryngol 280, 671–680. 18. Della Volpe A., De Lucia A., Ippolito V., et al. (2021) Use of a 3D reconstruction model in a patient with severe atresia auris for optimal placement of Bonebridge transcutaneous bone conduction implant. Eur Arch Otorhinolaryngol 278, 3559–3564. 19. Rienas W., Hubbell R., Toivonen J., et al. (2024) 3D printed temporal bones for preoperative simulation and planning. Am J Otolaryngol 45, 104340. 20. Gungor-Ozkerim P.S., Inci I., Zhang Y.S., et al. (2018) Bioinks for 3D bioprinting: an overview. Biomater Sci 6, 915–946. 21. Gao S., Nie T., Lin Y., et al. (2024) 3D printing tissue-engineered scaffolds for auricular reconstruction. Materials Today Bio 27, 101141. 22. Lan X., Liang Y., Erkut E.J.N., et al. (2021) Bioprinting of human nasoseptal chondrocytes-laden collagen hydrogel for cartilage tissue engineering. FASEB J 35, e21191. 23. Li L., Stiadle J.M., Lau H.K., et al. (2016) Tissue engineering-based therapeutic strategies for vocal fold repair and regeneration. Biomaterials 108, 91–110. 24. Murphy S.V. & Atala A. (2014) 3D bioprinting of tissues and organs. Nat Biotechnol 32, 773–785. 25. Jenks C.M., Patel V., Bennett B., et al. (2021) 3D middle ear model to teach anatomy and surgical skills. OTO Open 5, 2473974X211046598. Figures Legend Fig 1. Conceptual map describing 3d Bioprinting potential application and limits Reference Year Country Study design 3D Printing Technology Material Resolution Anatomical Structures Accuracy Validation Method Application Outcome Zhao et al. 2020 China Ossicular Tissue (Simulation Study) HRCT temporal bone axial scan + Philips Brilliance iCT 256-slice spiral CT and CAD of DICOM – – Ossicles 0.4 mm (after split-layer scanning). Kappa consistency test Ossicles reconstruction High accuracy of the visualization of the malleus and incus after restoration, good degree of restoration. The study needs further improvement. Della Volpe et al. 2021 Italy Temporal bones CT images acquired using a Siemens SOMATOM Definition dual source scanner + DICOM files uploaded into the MIMICS InPrint 3.0 software (Materialise NV, Leuven, Belgium). segmented model of the temporal bone was exported in standard tessellation language (STL) file format for editing and 3D printing with a printing system using additive technology (Raise 3d Pro Plus) with and polylactic acid (PLA) filaments. Polylactic acid (PLA) filaments – Bonebridge transcutaneous bone conduction – Hearing tests Patients affected by severe atresia auris (AA) The 3D model allowed to correctly pinpoint the best location in which to place the Bonebridge into the bone 2], thereby maximizing the patient’s auditory rehabilitation by obtaining a complete closure of the air–bone gap Markodimitraki et al. 2021 Netherlands Cochlear implantation Cone beam CT (CBCT) scans, followed by virtual planning of the CI position. Surgical, bone-supported drilling guides were designed to conduct a minimally invasive procedure and were 3D-printed (laser sintering 3D printing). Photopolymer resin (Model 2.0, Next-Den, Soesterberg, The Netherlands) – Temporal Bones High placement accuracy Statistics on Iterative Closest Point (ICP) algorithm Unilateral and bilateral cochlear implantation The surgical guide performed well in translational accuracy, showing more heterogeneity in rotational accuracy. The presented surgical guide confirm its potential to increase positioning accuracy in unilateral and bilateral cochlear implantations. Riemann et al. 2021 Germany Intracochlear Air Fused Deposition Modeling (FDM) PETG, Simubone™, Photopolymer resin 0.1 mm (FDM), 0.05 mm (DLP) Cochlea – Pressure measurements Cochlear implantation PETG and resin suitable for mastoidectomy Sokołowski, Orłowski, Bartoszewicz et al. 2023 Poland Ossicular prosthesis Cone-Beam Computed Tomography (CBCT) + OsiriX software. The incus model was processed using “3D Surface rendering” mode and exported to the stereolithography (STL) file. Prostheses were fabricated using a DWS DW 020D 3D printer, using stereolithographic (SLA) technology. Ultraviolet (UV) light-cured resin – Ossicular chain 0.05 mm Acoustic stimuli AND laser Doppler vibrometer (LDV) Patient-specific ossiculoplasty The reconstructed chain movability was characterized by statistically insignificant movability reduction at all tested frequencies. Sokołowski,Orłowski, Lachowska et al. 2023 Poland Ossicular prosthesis Cone-Beam Computed Tomography (CBCT) + OsiriX software. The incus model was processed using “3D Surface rendering” mode and exported to the stereolithography (STL) file. Prostheses were fabricated using a DWS DW 020D 3D printer, using stereolithographic (SLA) technology. Ultraviolet (UV) light-cured resin – Ossicular chain – Canal wall-up tympanoplasty Patient having chronic otitis media and ossicular chain defects The results experiment with designing and printing the 3D custom ossicular prosthesis and its Laser Doppler Vibrometer velocity measurements show it may be an interesting option for conductive hearing loss treatment De Angelis N et al. 2023 Italy Bone cells for rigenerative medicine Prusa Mini LCD ®3D printer (Prusa Research a.s., Prague, Czech Republic) Poly(ε-caprolactone) (PCL) + 20% beta-tricalcium phosphate (β-TCP), L-polylactic acid (PLLA) + 10% HA (synthetic hydroxyapatite) and PCL + 20% β-TCP – Bone regeneration – Statical Mechanical Tests (3 Points Bending Test Zwick Roell); Microscopic Morphological Analysis; immunofluorescence to evaluate biomarkers of MSC differentiation and maturation bone tissue engineering Both the polymeric matrices are highly biocompatible, and, in perspective, they may represent a viable option as scaffolds for bone regeneration. Freiser et al. 2024 USA Temporal Bone Dissection Stereolithography (SLA) White acrylic resin 0.625 mm Temporal bone – CT scan comparison Surgical training Effective for stepwise surgical training So J., et al 2022 South Korea Surgical planning of tumor 3D-printed bone model and the PSP; RS6000 3D printer (Uniotech, Shanghai, China). computer-aided 3D design software (3-DS Max; Autodesk, San Francisco, CA, USA) applied to the MRI and CT images 3-D printer (Style NEO-A22C; Cubicon) and polylactic acid filament (PLA filament; Cubicon). 0.2 mm Bone model for sphenoid-wing craniectomy – Postcontrast CT images were converted to stereolithography files. Segmentation, 3D model reconstruction, and prosthesis design were then performed using computer-aided design software (Mimics; Materialize NV, Leuven, Belgium) Precision surgery of Endoscopy-assisted resection The sphenoid-wing meningioma could be safely approached by endoscopy-assisted 3D-PSP without requiring neuronavigation. Xue et al. 2022 China Bone tissue engineering for bone defect treatment, focusing on scaffold materials, 3D printing technologies, and clinical applications in bone regeneration. stereolithography (SLA), selective laser sintering (SLS), fused deposition modeling (FDM), and direct ink writing (DIW). Inorganic biomaterials (e.g., titanium alloys, tantalum), bioceramics (e.g., hydroxyapatite, β-tricalcium phosphate), synthetic polymers (e.g., PLA, PGA), and natural biomaterials (e.g., collagen, chitosan) for developing scaffolds suitable for bone repair. – The scaffolds are designed for integration with various anatomical structures, such as cortical and trabecular bone, and are intended for areas including the skull, mandible, and long bone segments. – In vitro and in vivo testing Employment of 3D-printed scaffolds to repair critical bone defects, such as those from cranial injuries, as well as defects in long bones and alveolar bones. The scaffolds support bone regeneration and angiogenesis, essential for effective bone healing. Prevention and management of skeletal injuries is mainly to reduce the risk of bone stress injury. Freeman et al. 2021 Ireland Experimental Protocol description RegenHU 3D Discovery, Generation 1 Polycaprolactone (PCL) 30G needle, 3 mm/s feed rate Large bone defects – In vitro and in vivo testing Bone regeneration Enhanced bone regeneration with spatio-temporal control of growth factor delivery Shu et al. 2021 China Experimental validation 3D printing PLA 0.2 mm layer thickness Maxillofacial (TMJ) <5% difference Comparison of experimental and FE model strains Validationof FE models of TMJ Accurate simulation of TMJ interactions Stramiello et al. 2022 USA Prospective, proof-of-concept study Material jetting 3D printing Photopolymer (trade names Bone Matrix and Agilus 30) - Pediatric middle ear Adequate high anatomic fidelity Anatomy quizzes, survey Endoscopic ear surgery training model Validated as appropriate surgical simulator Gao et al. 2023 China 3D-printed calcium silicate artificial bone improved by a calcium sulfate-Cu2+ delivery system CeramBuilder 100pro Calcium silicate, calcium sulfate, Cu²⁺ 40 µm slice thickness, 120 µm curing depth Large bone defects – In vivo and in vitro analyses Bone repair Improved osteogenesis, angiogenesis, and antibacterial properties Westarp E. et al. 2024 Switzerland 3D technology for preplanned patient-specific implants external manufacturer based on the preplanned 3D data set, 3D-based premanufactured silicon mold Polyetheretherketone (PEEK) and customized Polymethylmethacrylate (PMMA) - Frontotemporal – Computer Tomography (CT) Bone reconstruction preplanned PEEK for template-based craniectomies or custom-made molds for intraoperative PMMA cranioplasty facilitate one-stage cranioplasty after resection of intraosseous meningiomas, provide exact reconstruction of even complex cranial geometries and suitable patients’ satisfaction Balazova K et al. 2024 Czech Republic 3D printed temporal bone models with different levels of complexity Conventional fused filament fabrication 3D printer Original Prusa i3 MK3S+ and polylactic acid filament Design of 3D printed temporal bone models with different levels of complexity. The endoscope resolution is reduced with growing distance from the surgical field (it is more significant for the 0° endoscope). Temporal bone models – Image analysis or visibility of anatomical structures to compare 0° or 30° endoscopes surgery Both types of endoscopes have advantages and disadvantages, and the choice depends on the surgeon’s personal preference and on the type of planned procedure. Frendø et al. 2021 Denmark Prospective trial Visual Ear Simulator – – Temporal bone 33% improvement in VR, 21% improvement in 3D-printed model Performance scores using CISAT Cochlear implant surgery training VR SBT improves CI surgery skills Freiser et al. 2021 USA Temporal bones Micro CT scan and Consumer-level SLA 3D printer Acrylic resin materials, Acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA) 0.15 mm Mastoidectomy 0.625 mm Statistics between different experience levels for mastoidectomy Promising method to employ for formative and summative evaluations. The employment of a consumer-level 3D printer results favorably for mastoidectomy case preparation Ock et al. 2023 Seoul Mastoidectomy CT scan + Stereolithography White resin post-cured at 60 °C for 30 min High-resolution Mastoidectomy 0.01 mm measuring the screw insertion torque for infll specimens and cadaveric temporal bones and investigating its usability with a fve-point Likert-scale questionnaire completed by fve otolaryngologists. Realistic Training analyze the reliability and challenges of radiomics in MR imaging protocols. Goyanes et al. 2016 England 3D scanning and 3D printing Stereolithography (SLA) NF (NinjaFlex® red filament, thermoplastic polyurethane); FPLA (Flex EcoPLA™ BLUE 45D filament, flexible polylactic acid);PCL (Polycaprolactone, 6-caprolactone polymer, (C6H10O2)n, MW:80,000 Da); PEGDA (poly(ethylene glycol) diacrylate, MW: 700 Da); PEG (poly(ethylene glycol) 300, MW: 300 Da) and diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide Salicylic acid; Tetrahydrofuran (THF, HPLC grade); dichloromethane (DCM, ≥99.5% purity); methanol (≥99.9% purity, HPLC grade). point-to-point spacing of 0.65 mm, Nose-shaped mask – Mechanical, Thermal, X-rays powder diffraction, SEM, Diffusion Studies SLA printing is a convenient and promising SLA printing involves a one-step process that leads to 3D printed devices Rienas W. et al. 2024 USA Case series Projet 5500X-E 3D printer with CE-NT amber soft resin for facial nerve and cholesteatoma, CR-CL hard translucent resin for bony structures; 32 µm layer thickness CE-NT amber soft resin for facial nerve and cholesteatoma, CR-CL hard translucent resin for bony structures 32 µm layer thickness Temporal bone, cochlea, internal auditory canal (IAC), semicircular canals, facial nerve, cholesteatoma 0.1-0.5 mm margin of error Comparison of preoperative 3D printed models with intraoperative findings and outcomes Preoperative planning and simulation for cochlear implantation and cholesteatoma surgery; training for surgical techniques and approaches Reduced operative time and costs, improved safety and efficacy, avoidance of complications, enhanced surgical planning and intraoperative referencing, successful surgeries without complications Leonov et al. 2022 Russia Design and validation of a phantom for transcranial ultrasonography FDM and LCD PLA, Photopolymer resin 50 µm (FDM), 31 µm (LCD) Skull, Brain 31 µm Ultrasonography and CT scan Transcranial ultrasonography Effective for training and research Cafino et al. 2024 Philippines Experimental study - Materials evaluation for 3D printing FDM and DLP PETG, Simubone™, Photopolymer resin 0.1 mm (FDM), 0.05 mm (DLP) Temporal bone – CT scan comparison Surgical simulation Resin models most accurate Tapiala J et al. 2024 Finland Mastoidectomy on a 3D-printed temporal bone model after Virtual reality training 3D-printed temporal bone models (Temporal Bone Patient “Schmidt”, Phacon, USA, Atlanta) – – Mastoidectomy – VR temporal bone model vs. traditional anatomy books Training on mastoidectomy surgery Utilization of VR training in complete novices as it has higher trainee satisfaction Shehzad A et al. 2023 Kazakhstan Bone tissue engineering 3D Bioprinting by BioX 3D printer (CELLINK, Goteborg, Sweden) Gelatin methacryloyl (GelMA) mixed with 1% w/v alginate solution, Rat mesenchymal stem cells (rMSCs) High-resolution 3D-printed hydrogel scaffolds bone tissue ca. 90% Nuclear magnetic resonance (NMR) proton spectra of unfunctionalized and methacrylated gelatin. Rheometer (Anton Paar, MCR302, Graz, Austria) was used to test the hydrogel inks’ mechanical and viscoelastic properties. Calcein-AM (green fluorescence) stains for live cells and ethidium homodimer (red fluorescence) for dead cells. The osteogenic differentiation was observed on the bioprinted scaffold by evaluating the alkaline phosphatase (ALP) activity using the ALP ELISA kit. Histological evaluation for mineralization and ECM, calcium deposition Bone tissue engineering The demonstrated approach implemented on optimized hydrogel ink formulation offers a simple yet effective technique for fabricating high-precision 3D-printed hydrogel scaffolds bone tissue engineering as well as other related applications Razavi et al. 2021 USA Experimental study on 3D printing Stereolithographic – – Middle ear with stapedotomy site Able to detect force range of 1.2 to 5200 mN Experimental calculation of torsional spring constant Low-cost training model for surgical management of otosclerosis Developed model with measurable objective outcomes Ding et al. 2022 USA 4D biofabrication Instantly generated graded hydrogel scaffolds PEG, Alginate, Gelatin derivatives – Bone-like tissue – Cell viability, DNA content, ALP activity, Calcium deposition Tissue engineering Demonstrated feasibility of 4D biofabrication for bone tissue engineering with high cell viability and osteogenic differentiation He et al. 2021 China Experimental study on 3D printing Photonic Hyperthermia of Osteosarcoma CaCO3-PCL High-resolution Bone (Osteosarcoma) – In vitro and in vivo tests Photothermal therapy and bone regeneration Effective OS elimination and enhanced bone regeneration Brown et al. 2022 USA Temporal bones Objet350 Connex3 3D printer Patented (not specified) – Temporal Bones – Standardized blast test model The pressure measurements in the 3D printed Temporal Bone (TB) demonstrated that the developed 3D printed TB is a valid model for testing passive Hearing Protection Device designs. It was demonstrated that the developed 3D printed TB is a valid model for testing passive Hearing Protection Device designs. de Souza et al. 2023 Brazil Temporal bones Descriptive qualitative study CT scan + Form Labs 3L printer Light-curing resin (Formlabs White Resin). Nylon filaments were embedded in their pathways represented the facial, cochlear, and vestibular nerves, during the printing. The cholesteatoma was represented by silicone glue deposited on the topography occupied by the lesion. High-resolution Temporal bone with cholesteatoma – MiSSES template, Likert-scale questionnaire Training in otologic surgery for cholesteatoma High fidelity, low cost, replicability, educational value; The model demonstrated adequate face and content validity and provided an anatomically realistic dissection experience with educational value. Jenks et al. 2021 USA Middle ear and external auditory canal (model study) CT + Pixologic ZBrush in which import segmentation. Structures not captured on segmentation were scupted using Maxon Cinema 4D R21. The model was processed on GrabCAD studios and printed on a Stratasys J750 printer. – – Middle ear and external auditory canal – Otoendoscopy Study of middle ear anatomy This model represents an advancement in otologic surgical simulation to be used for both anatomic teaching and otoendoscopic surgical skills acquisition. Lahde et al. 2024 Finland Middle ear 3D printer SE Plus material extrusion based Liquid photopolymer Clear V4 18.8 µm Middle ear – Ossiculoplasty Development of a functional mid-dle ear model. This middle ear model is suitable for ossiculoplasty practice with regular commercial prostheses or with 3D-printed practice prostheses. Posta et al. 2022 Hungary Cochlear implantation CT scan + RadiAnt DICOM viewer Cochlear Osia 2 system (Titanium Implant) High-resolution Cochlear implantation – Measure of bone and soft tissue thickness from retrospective examination of cranial CT scans of 5-12 year old patiens, using also 3D printed temporal bones. Pediatric Population 3 mm BI300 implants results the best choice;a slight superior positioning of the implant may prevent breaching the mastoid air cells. Preoperative CT is unnecessary for Osia(R) implantation in non-complicated cases. Veres et al. 2021 Hungary Radiomics phantom analysis Fused Deposition Modeling (FDM) Polylactic Acid (3DJake ecoPLA, White) - 1-2 mm – – Textures for analyzing the reliability of radiomic data from MR scans. Radiomic data evaluation Three-dimensional-printed QR codes provide a unique opportunity to analyze the reliability and challenges of radiomics in MR imaging protocols El Chemaly et al. 2023 USA Protocol validation Calibration of an electromagnetically tracked surgical stereo microscope for augmented reality visualization – 0.11 ± 0.06 mm in 2D, 0.98 ± 0.13 mm in 3D. Middle and inner ear 0.98 ± 0.13 mm in 3D Registration error calculation Augmented reality visualization in microscopic surgery Improving of operative safety by allowing the 3D visualization of anatomical structures from preoperative computed tomography (CT) scans on real intraoperative microscope video feed. \sout \sout \sout \sout \sout \sout Table I. Literature evidence on 3d bio-printing. Technologies and materials used, anatomical structures targeted, validation methods applied, and key outcomes achieved are described. Abbreviations : AR, Augmented Reality; AR, Augmented Reality; CBCT, Cone Beam Computed Tomography; CT, Computed Tomography; DICOM, Dig Imaging and Communications in Medicine; DLP, Digital Light Processing; EM, Electromagnetic; FE, Finite Element; FD. Deposition Modeling; HA, Hydroxyapatite; HRCT, High-Resolution Computed Tomography; ICP, Iterative Closest Point; MRI, Magnetic Resonance Imaging; PLA, Polylactic Acid; PCL, Polycaprolactone; PMMA, Polymethylmethacrylate; PSP, Patient-Specific Pointer; RE, Registration Error; SLA, Stereolithography; SLS, Selective Laser Sintering; STL, Standard Tessellation Language; TCP, Tricalcium Phosphate; TMJ, Temporomandibular Joint; VR, Virtual Reality; 3D, Three-Dimensional; 4D, Four-Dimensional (dynamic bioprinting involving time as an additional factor). Information & Authors Information Version history V1 Version 1 28 April 2025 Peer review timeline Published Clinical Otolaryngology Version of Record 14 May 2025 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Collection Clinical Otolaryngology Authors Affiliations Alfio Torrisi 0000-0003-2404-5062 Universita degli Studi di Enna 'Kore' View all articles by this author Mario Lentini Universita degli Studi di Enna 'Kore' View all articles by this author Salvatore Pezzino Universita degli Studi di Enna 'Kore' View all articles by this author Caterina Gagliano 0000-0001-8424-0068 Universita degli Studi di Enna 'Kore' View all articles by this author Salvatore Lavalle Universita degli Studi di Enna 'Kore' View all articles by this author Jerome Rene Lechien Universite de Mons Faculte de Medecine Pharmacie et Sciences Biomedicales View all articles by this author Roberta Malaguarnera Universita degli Studi di Enna 'Kore' View all articles by this author Sergio Castorina Centro Clinico Diagnostico GB Morgagni Srl View all articles by this author Filippo Torrisi Universita degli Studi di Enna 'Kore' View all articles by this author A. Maniaci [email protected] Universita degli Studi di Enna 'Kore' View all articles by this author Metrics & Citations Metrics Article Usage 350 views 191 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Alfio Torrisi, Mario Lentini, Salvatore Pezzino, et al. The Promise and Challenges of 3D Bioprinting in Otolaryngology: A Contemporary Perspective Viewpoint.. Authorea . 28 April 2025. DOI: https://doi.org/10.22541/au.174582249.96179914/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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