Core Legal Challenges for Medical 3D Printing in the EU.

3D printing has been adopted into routine use for certain medical applications, but more widespread usage has been hindered by, among other things, unclear legislation. We performed an analysis, using legal doctrinal study and legal informatics, of relevant EU legislation and case law in four issues relevant to medical 3D printing (excluding bioprinting or pharmacoprinting): pre-market approval, post-market liability, intellectual property rights, and data protection. Several gaps and uncertainties in the current legislation and interpretations were identified. In particular, we regard the current EU regulatory framework to be quite limiting and inflexible, exemplifying a cautionary approach common in EU law. Though the need to establish high safety standards in order to protect patients as a disadvantaged population is understood, both legal uncertainties and overregulation are seen as harmful to innovation. Hence, more adaptive legislation is called for to ensure continuous innovation efforts and enhanced patient outcomes.

Metal Laser-Based Powder Bed Fusion Process Development Using Optical Tomography.

In this study, a set of 316 L stainless steel test specimens was additively manufactured by laser-based Powder Bed Fusion. The process parameters were varied for each specimen in terms of laser scan speed and laser power. The objective was to use a narrow band of parameters well inside the process window, demonstrating detailed parameter engineering for specialized additive manufacturing cases. The process variation was monitored using Optical Tomography to capture light emissions from the layer surfaces. Process emission values were stored in a statistical form. Micrographs were prepared and analyzed for defects using optical microscopy and image manipulation. The results of two data sources were compared to find correlations between lack of fusion, porosity, and layer-based energy emissions. A data comparison of Optical Tomography data and micrograph analyses shows that Optical Tomography can partially be used independently to develop new process parameters. The data show that the number of critical defects increases when the average Optical Tomography grey value passes a certain threshold. This finding can contribute to accelerating manufacturing parameter development and help meet the industrial need for agile component-specific parameter development.

Integration of 3D-printed middle ear models and middle ear prostheses in otosurgical training.

BACKGROUND: In otosurgical training, cadaveric temporal bones are primarily used to provide a realistic tactile experience. However, using cadaveric temporal bones is challenging due to their limited availability, high cost, and potential for infection. Utilizing current three-dimensional (3D) technologies could overcome the limitations associated with cadaveric bones. This study focused on how a 3D-printed middle ear model can be used in otosurgical training. METHODS: A cadaveric temporal bone was imaged using microcomputed tomography (micro-CT) to generate a 3D model of the middle ear. The final model was printed from transparent photopolymers using a laser-based 3D printer (vat photopolymerization), yielding a 3D-printed phantom of the external ear canal and middle ear. The feasibility of this phantom for otosurgical training was evaluated through an ossiculoplasty simulation involving ten otosurgeons and ten otolaryngology-head and neck surgery (ORL-HNS) residents. The participants were tasked with drilling, scooping, and placing a 3D-printed partial ossicular replacement prosthesis (PORP). Following the simulation, a questionnaire was used to collect the participants' opinions and feedback. RESULTS: A transparent photopolymer was deemed suitable for both the middle ear phantom and PORP. The printing procedure was precise, and the anatomical landmarks were recognizable. Based on the evaluations, the phantom had realistic maneuverability, although the haptic feedback during drilling and scooping received some criticism from ORL-HNS residents. Both otosurgeons and ORL-HNS residents were optimistic about the application of these 3D-printed models as training tools. CONCLUSIONS: The 3D-printed middle ear phantom and PORP used in this study can be used for low-threshold training in the future. The integration of 3D-printed models in conventional otosurgical training holds significant promise.

Feasibility of 3D-printed middle ear prostheses in partial ossicular chain reconstruction.

Despite advances in prosthesis materials, operating microscopes and surgical techniques during the last 50 years, long-lasting hearing improvement remains a challenge in ossicular chain reconstruction. Failures in the reconstruction are mainly due to inadequate length or shape of the prosthesis, or defects in the surgical procedure. 3D-printed middle ear prosthesis might offer a solution to individualize treatment and obtain better results. The aim of the study was to study the possibilities and limitations of 3D-printed middle ear prostheses. Design of the 3D-printed prosthesis was inspired by a commercial titanium partial ossicular replacement prosthesis. 3D models of different lengths (1.5-3.0 mm) were created with Solidworks 2019-2021 software. The prostheses were 3D-printed with vat photopolymerization using liquid photopolymer Clear V4. Accuracy and reproducibility of 3D printing were evaluated with micro-CT imaging. The acoustical performance of the prostheses was determined in cadaver temporal bones with laser Doppler vibrometry. In this paper, we present an outline of individualized middle ear prosthesis manufacturing. 3D printing accuracy was excellent when comparing dimensions of the 3D-printed prostheses and their 3D models. Reproducibility of 3D printing was good if the diameter of the prosthesis shaft was 0.6 mm. 3D-printed partial ossicular replacement prostheses were easy to manipulate during surgery even though they were a bit stiffer and less flexible than conventional titanium prostheses. Their acoustical performance was similar to that of a commercial titanium partial ossicular replacement prosthesis. It is possible to 3D print functional individualized middle ear prostheses made of liquid photopolymer with good accuracy and reproducibility. These prostheses are currently suitable for otosurgical training. Further research is needed to explore their usability in a clinical setting. In the future, 3D printing of individualized middle ear prostheses may provide better audiological outcomes for patients.

Legal issues and underexplored data protection in medical 3D printing: A scoping review.

Introduction: 3D printing has quickly found many applications in medicine. However, as with any new technology the regulatory landscape is struggling to stay abreast. Unclear legislation or lack of legislation has been suggested as being one hindrance for wide-scale adoption. Methods: A scoping review was performed in PubMed, Web of Science, SCOPUS and Westlaw International to identify articles dealing with legal issues in medical 3D printing. Results: Thirty-four articles fulfilling inclusion criteria were identified in medical/technical databases and fifteen in the legal database. The majority of articles dealt with the USA, while the EU was also prominently represented. Some common unresolved legal issues were identified, among them terminological confusion between custom-made and patient-matched devices, lack of specific legislation for patient-matched products, and the undefined legal role of CAD files both from a liability and from an intellectual property standpoint. Data protection was mentioned only in two papers and seems an underexplored topic. Conclusion: In this scoping review, several relevant articles and several common unresolved legal issues were identified including a need for terminological uniformity in medical 3D printing. The results of this work are planned to inform our own deeper legal analysis of these issues in the future.

3D Printing, Intellectual Property Rights and Medical Emergencies: In Search of New Flexibilities.

The COVID-19 pandemic has exponentially accelerated the use of 3D printing (3DP) technologies in healthcare. Surprisingly, though, we have seen hardly any public intellectual property right (IPR) disputes concerning the 3D-printed medical equipment produced to cope with this crisis. Yet it can be assumed that a great variety of IPRs could potentially have been enforced against the use of various items of equipment printed out without express consent from IP holders. Many reasons might have motivated IP owners not to enforce their rights during the pandemic, such as the fear of acquiring a bad reputation during a declared situation of national emergency. There is no internationally recognised general exception to IPR enforcement for health emergencies, while several - sometimes ineffective - tools, like compulsory licensing, voluntary licensing arrangements and potential TRIPS waivers, have been considered or used to facilitate access to and the distribution of innovations in critical situations. During the COVID-19 emergency, this has meant that the 3DP community has been operating in a state of relative uncertainty including with regard to the risks of IP infringement. This study contextualises these issues for pandemic-relevant 3DP. Building upon experience gathered during the COVID-19 pandemic, we look to the future to see what novel mechanisms within the IPR system could provide the additional flexibility required for dealing more smoothly, with the help and support of digital technologies, with situations such as global health emergencies.

Microstructure and Properties of Additively Manufactured AlCoCr0.75Cu0.5FeNi Multicomponent Alloy: Controlling Magnetic Properties by Laser Powder Bed Fusion via Spinodal Decomposition.

A non-equiatomic AlCoCr0.75Cu0.5FeNi alloy has been identified as a potential high strength alloy, whose microstructure and consequently properties can be widely varied. In this research, the phase structure, hardness, and magnetic properties of AlCoCr0.75Cu0.5FeNi alloy fabricated by laser powder bed fusion (LPBF) are investigated. The results demonstrate that laser power, scanning speed, and volumetric energy density (VED) contribute to different aspects in the formation of microstructure thus introducing alterations in the properties. Despite the different input parameters studied, all the as-built specimens exhibit the body-centered cubic (BCC) phase structure, with the homogeneous elemental distribution at the micron scale. A microhardness of up to 604.6 ± 6.8 HV0.05 is achieved owing to the rapidly solidified microstructure. Soft magnetic behavior is determined in all as-printed samples. The saturation magnetization (Ms) is dependent on the degree of spinodal decomposition, i.e., the higher degree of decomposition into A2 and B2 structure results in a larger Ms. The results introduce the possibility to control the degree of spinodal decomposition and thus the degree of magnetization by altering the input parameters of the LPBF process. The disclosed application potentiality of LPBF could benefit the development of new functional materials.

Modeling, Simulation and Data Processing for Additive Manufacturing.

Additive manufacturing or, more commonly, 3D printing is one of the fundamental elements of Industry 4 [...].

Additive Manufacturing for Localized Medical Parts Production: A Case Study.

Centralized supply chains (SCs) are prone to disruption, which makes them a risky choice for medical equipment production. Additive manufacturing (AM) allows for production localization and improvements in SC resilience. However, the comparative competitiveness of a localized SC from the time and cost perspective is still unclear. In this study, we investigate the competitiveness of localized medical part AM SCs against centralized ones by analyzing the responsiveness and cost of each SC. We utilize a real-world case study in which an AM service provider supplies medical parts to university medical centers in the Netherlands to construct six scenarios. We also develop a thorough empirical cost formulation for both central and local AM of patient-specific medical parts. The results of scenario analysis show that when utilizing the currently available AM technology, localized SC configurations significantly reduce the delivery time from about 54 to 27h, but at a 4.3-fold higher cost. Hence, we illustrate that the cost difference between the localized and centralized scenarios can be reduced when state-of-the-art AM machines are utilized, demand volumes increase, and the distances between the SC network nodes expand. Moreover, our scenario analysis confirms that the cost of the measures taken to prevent dust dispersion associated with powder-bed fusion AM has a major impact on the total cost of localized AM SCs for medical parts. The results of this study contribute to the understanding of the relevant factors in deciding whether central or localized SC configurations can be used in the AM production of medical parts. Furthermore, this study provides managerial insights for decision-makers at governments and hospitals as well as AM service providers and AM equipment manufacturers.

Additive Manufacturing of Resected Oral and Oropharyngeal Tissue: A Pilot Study.

Better visualization of tumor structure and orientation are needed in the postoperative setting. We aimed to assess the feasibility of a system in which oral and oropharyngeal tumors are resected, photographed, 3D modeled, and printed using additive manufacturing techniques. Three patients diagnosed with oral/oropharyngeal cancer were included. All patients underwent preoperative magnetic resonance imaging followed by resection. In the operating room (OR), the resected tissue block was photographed using a smartphone. Digital photos were imported into Agisoft Photoscan to produce a digital 3D model of the resected tissue. Physical models were then printed using binder jetting techniques. The aforementioned process was applied in pilot cases including carcinomas of the tongue and larynx. The number of photographs taken for each case ranged from 63 to 195. The printing time for the physical models ranged from 2 to 9 h, costs ranging from 25 to 141 EUR (28 to 161 USD). Digital photography may be used to additively manufacture models of resected oral/oropharyngeal tumors in an easy, accessible and efficient fashion. The model may be used in interdisciplinary discussion regarding postoperative care to improve understanding and collaboration, but further investigation in prospective studies is required.

Additive Manufacturing Processes in Medical Applications.

Additive manufacturing (AM, 3D printing) is used in many fields and different industries. In the medical and dental field, every patient is unique and, therefore, AM has significant potential in personalized and customized solutions. This review explores what additive manufacturing processes and materials are utilized in medical and dental applications, especially focusing on processes that are less commonly used. The processes are categorized in ISO/ASTM process classes: powder bed fusion, material extrusion, VAT photopolymerization, material jetting, binder jetting, sheet lamination and directed energy deposition combined with classification of medical applications of AM. Based on the findings, it seems that directed energy deposition is utilized rarely only in implants and sheet lamination rarely for medical models or phantoms. Powder bed fusion, material extrusion and VAT photopolymerization are utilized in all categories. Material jetting is not used for implants and biomanufacturing, and binder jetting is not utilized for tools, instruments and parts for medical devices. The most common materials are thermoplastics, photopolymers and metals such as titanium alloys. If standard terminology of AM would be followed, this would allow a more systematic review of the utilization of different AM processes. Current development in binder jetting would allow more possibilities in the future.

Three-Dimensional Presentation of Tumor Histopathology: A Model Using Tongue Squamous Cell Carcinoma.

Medical imaging often presents objects in three-dimensional (3D) form to provide better visual understanding. In contrast, histopathology is typically presented as two-dimensional (2D). Our objective was to present the tumor dimensions in 3D by creating a 3D digital model of it and so demonstrate the location of the tumor and the histological slices within the surgical soft tissue resection specimen. We developed a novel method for modeling a tongue squamous cell carcinoma using commonly available instruments. We established our 3D-modeling method by recognizing and solving challenges that concern the selection of the direction of histological slices. Additional steps to standard handling included scanning the specimen prior to grossing and modeling the carcinoma, which required only a table scanner and modeling software. We present challenges and their solutions in modeling the resection specimen and its histological slices. We introduce a finished 3D model of a soft tissue resection specimen and the actual tumor as well as its histopathological grossing sites in 3D digital and printed form. Our novel method provides steps to create a digital model of soft tissue resection specimen and the tumor within. To our knowledge, this is the first attempt to present histopathological margins of a tongue tumor in 3D form, whereas previously, only 2D has been available. The creation of the 3D model does not call for predetermined grossing directions for the pathologist. In addition, it provides a crucial initiative to enhance oncological management. The method allows a better visual understanding of tumor margins, topography, and orientation. It thus provides a tool for an improved postoperative assessment and aids, for example, in the discussion of the need for additional surgery and adjuvant therapy.

Three-dimensional printed surgical templates for fresh cadaveric osteochondral allograft surgery with dimension verification by multivariate computed tomography analysis.

BACKGROUND: The fit of the allograft is a particular concern in fresh cadaveric osteochondral allograft (FOCA) surgery. Digital design and fabrication were utilized in conjunction with traditional surgery to enable efficient discovery and reproduction of appropriately dimensioned allograft. METHODS: A patient with large osteochondral defects in the lateral femoral condyle was to undergo FOCA surgery. A digital virtual operation was performed, based on computed tomography (CT) images of the patient. Polyamide saw templates were manufactured using a selective laser sintering process, and gypsum powder was used to manufacture preoperative and intraoperative medical models with binder jetting process. The design dimensions were verified numerically by determining the intactness of the section surface and allograft volume based on four independent measurements of the initial design, and an automated design optimization strategy was postulated. For the surgery, a lateral longitudinal approach was employed. RESULTS: The virtual operation allowed an efficient design of the saw templates. Their shape and dimensions were verified with a numerical CT analysis method. The allograft dimensions (medial-lateral/superior-inferior/anterior-posterior) were approximately 40/28.5/24 mm, respectively, with the anterosuperior corner diagonally removed, yielding a section volume of approximately 16.5 cm3. These manually chosen dimensions were reminiscent of the corresponding computationally optimized values. CONCLUSIONS: Use of computer-aided design in virtual operation planning and three-dimensional printing in the fabrication of designed templates allowed for an efficient FOCA procedure and accurate allograft fitting. The numerical optimization method allowed for a semiautomated design process, which could in turn be realized also with surgical navigation or robotic surgery methods.

Implementation of Industrial Additive Manufacturing: Intelligent Implants and Drug Delivery Systems.

The purpose of this study is to demonstrate the ability of additive manufacturing, also known as 3D printing, to produce effective drug delivery devices and implants that are both identifiable, as well as traceable. Drug delivery devices can potentially be used for drug release in the direct vicinity of target tissues or the selected medication route in a patient-specific manner as required. The identification and traceability of additively manufactured implants can be administered through radiofrequency identification systems. The focus of this study is to explore how embedded medication and sensors can be added in different additive manufacturing processes. The concept is extended to biomaterials with the help of the literature. As a result of this study, a patient-specific drug delivery device can be custom-designed and additively manufactured in the form of an implant that can identify, trace, and dispense a drug to the vicinity of a selected target tissue as a patient-specific function of time for bodily treatment and restoration.

In vitro cytotoxicity and surface topography evaluation of additive manufacturing titanium implant materials.

Custom-designed patient-specific implants and reconstruction plates are to date commonly manufactured using two different additive manufacturing (AM) technologies: direct metal laser sintering (DMLS) and electron beam melting (EBM). The purpose of this investigation was to characterize the surface structure and to assess the cytotoxicity of titanium alloys processed using DMLS and EBM technologies as the existing information on these issues is scarce. "Processed" and "polished" DMLS and EBM disks were assessed. Microscopic examination revealed titanium alloy particles and surface flaws on the processed materials. These surface flaws were subsequently removed by polishing. Surface roughness of EBM processed titanium was higher than that of DMLS processed. The cytotoxicity results of the DMLS and EBM discs were compared with a "gold standard" commercially available titanium mandible reconstruction plate. The mean cell viability for all discs was 82.6% (range, 77.4 to 89.7) and 83.3% for the control reconstruction plate. The DMLS and EBM manufactured titanium plates were non-cytotoxic both in "processed" and in "polished" forms.

Possibilities of Preoperative Medical Models Made by 3D Printing or Additive Manufacturing.

Most of the 3D printing applications of preoperative models have been focused on dental and craniomaxillofacial area. The purpose of this paper is to demonstrate the possibilities in other application areas and give examples of the current possibilities. The approach was to communicate with the surgeons with different fields about their needs related preoperative models and try to produce preoperative models that satisfy those needs. Ten different kinds of examples of possibilities were selected to be shown in this paper and aspects related imaging, 3D model reconstruction, 3D modeling, and 3D printing were presented. Examples were heart, ankle, backbone, knee, and pelvis with different processes and materials. Software types required were Osirix, 3Data Expert, and Rhinoceros. Different 3D printing processes were binder jetting and material extrusion. This paper presents a wide range of possibilities related to 3D printing of preoperative models. Surgeons should be aware of the new possibilities and in most cases help from mechanical engineering side is needed.

A novel classification and online platform for planning and documentation of medical applications of additive manufacturing.

Additive manufacturing technologies are widely used in industrial settings and now increasingly also in several areas of medicine. Various techniques and numerous types of materials are used for these applications. There is a clear need to unify and harmonize the patterns of their use worldwide. We present a 5-class system to aid planning of these applications and related scientific work as well as communication between various actors involved in this field. An online, matrix-based platform and a database were developed for planning and documentation of various solutions. This platform will help the medical community to structurally develop both research innovations and clinical applications of additive manufacturing. The online platform can be accessed through http://www.medicalam.info.

Imaging requirements for medical applications of additive manufacturing.

Additive manufacturing (AM), formerly known as rapid prototyping, is steadily shifting its focus from industrial prototyping to medical applications as AM processes, bioadaptive materials, and medical imaging technologies develop, and the benefits of the techniques gain wider knowledge among clinicians. This article gives an overview of the main requirements for medical imaging affected by needs of AM, as well as provides a brief literature review from existing clinical cases concentrating especially on the kind of radiology they required. As an example application, a pair of CT images of the facial skull base was turned into 3D models in order to illustrate the significance of suitable imaging parameters. Additionally, the model was printed into a preoperative medical model with a popular AM device. Successful clinical cases of AM are recognized to rely heavily on efficient collaboration between various disciplines - notably operating surgeons, radiologists, and engineers. The single main requirement separating tangible model creation from traditional imaging objectives such as diagnostics and preoperative planning is the increased need for anatomical accuracy in all three spatial dimensions, but depending on the application, other specific requirements may be present as well. This article essentially intends to narrow the potential communication gap between radiologists and engineers who work with projects involving AM by showcasing the overlap between the two disciplines.

Inaccuracies in additive manufactured medical skull models caused by the DICOM to STL conversion process.

INTRODUCTION: The process of fabricating physical medical skull models requires many steps, each of which is a potential source of geometric error. The aim of this study was to demonstrate inaccuracies and differences caused by DICOM to STL conversion in additively manufactured medical skull models. MATERIAL AND METHODS: Three different institutes were requested to perform an automatic reconstruction from an identical DICOM data set of a patients undergoing tumour surgery into an STL file format using their software of preference. The acquired digitized STL data sets were assessed and compared and subsequently used to fabricate physical medical skull models. The three fabricated skull models were then scanned, and differences in the model geometries were assessed using established CAD inspection software methods. RESULTS: A large variation was noted in size and anatomical geometries of the three physical skull models fabricated from an identical (or "a single") DICOM data set. CONCLUSIONS: A medical skull model of the same individual can vary markedly depending on the DICOM to STL conversion software and the technical parameters used. Clinicians should be aware of this inaccuracy in certain applications.