Three-Dimensional Printing of Patient-Specific Titanium Plates in Jaw Surgery: A Pilot Study

Study Overview
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Brief Summary
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Medical titanium plates are routinely used in fixing mobilized bone segments in jaw surgeries. Generally these plates are commercialized with standard construction specifications. Thus they should be repeatedly bended and arched to match the contour of anchored jaw bones before located in place and fastened by screws. To prevent stress fatigue induced by plate bending and improve structural design, we utilized the three-dimensional printing technique and developed a new production procedure in fabricating customized titanium plates according to each patient's specific skeletal contours and dimensions derived from medical imaging data. In general, the three-dimensional printing of customized implants are expected to facilitate surgical operation, reduce application duration and improve precise restoration. Up until now, the application of three-dimensional printing of titanium fixation plates in jaw surgery has been available only at two centers globally. The published preliminary work have proved the prospect of customized titanium plates in promoting mandibular reconstruction surgery and upper maxilla orthognathic surgery though their printed titanium plates looked rather bulky and the sample sizes were small and there is still lack of qualified randomized controlled trials between the printed and the conventional titanium plates. To better benefit from the burgeoning use of three-dimensional printing in health care, it is imperative to conduct a feasibility study in exploring the application of three-dimensional printing of titanium fixation plates in jaw surgery based on our patients. The aim of the study is to conduct a case series study focusing on the feasibility and safety of applying three-dimensional printed titanium plates in jaw reconstruction surgery and orthognathic surgery. The outcome measures include the success rate, potential adverse events and accuracy. A sample size of 48 subjects will be recruited prospectively. Considering the facts that titanium plates are widely used in jaw surgery and our unit is the largest oral and maxillofacial surgery center in Hong Kong, the well-designed customized titanium plate is therefore with great potential benefit for the patients in our population. Furthermore, the well-developed three-dimensional manufacturing protocol could also be applied in other relevant medical areas and push forward the personalized medicine era in the future.

Detailed Description
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Plate osteosynthesis is the basic philosophy in maintaining skeletal stabilization in jaw surgery. Numerous branded osteosynthesis systems are available and most of them are made from pure titanium or titanium alloys with standard construction specifications. Usually these titanium plates should be bended and arched to better match the three-dimensional contour of anchored jaw bones. However the optimal bending of the titanium plate sometimes is difficult and time-consuming especially for the inexperienced surgeons and in complicated cases. Excessive bending could also initiate residual stress and potentially worsen the mechanical properties of titanium plates(1). The three-dimensional (3D) printing, or additive manufacturing, has been well developed in fabricating customized materials from the computer-generated digital files. In recent years, 3D printing of patient-specific medical implants has been evolving with the newly-emerged technology of powder bed fusion, which enabled the melting of metals and further shaping of devices(2). In September 2015, China's innovative 3D printed hip joint prosthesis was commercially certified by China's State Food and Drug Administration. In February 2016, the world's first 3D printed patient-specific titanium cranial/craniofacial plate implant got the U.S. Food and Drug Administration's approval. Beyond that, a number of other printed implants have showed excellent performance in clinical research. These printed medical implants are majorly from pure titanium or Ti6Al4V alloy, which exhibit good resistance to fatigue and corrosion and are considered the most biocompatible metal(3). Relying on individualized imaging data, the printed implants are patient-specific and adapt to the anatomical structures precisely. Since the additive manufacturing is ultimately different from the conventional multi-step production operations, it could reduce costs and lead times, especially in printing complex devices for individualized cases. While in clinical applications, 3D printing of customized implants are expected to facilitate surgical operation, reduce application duration and improve precise restoration(4). It is predicted the application of 3D printing technique in medical area may bring forward another major advance toward personalized medicine(5). Many more customized medical implants will be approved in the future across the world. With the advent of metal additive manufacturing, the 3D-printed patient-specific titanium plates have been successfully fabricated. In 2012, Per Derand et al. reported the first application of 3D-printed titanium plates with the established workflow from imaging, via virtual design, to manufacturing of cutting guide and customized titanium reconstruction plates, and its utility in the fibula-based mandibular reconstruction surgery. The pre-printed plates did facilitate the operation and reduced the operation duration about half an hour though the postoperative accuracy of the grafted bone was modest compared with the virtual planning(6). Simultaneously, Leonardo Ciocca et al. reported the computer-aided designing and manufacturing in guiding secondary mandibular reconstruction of a discontinuity defect involving the employment of the surgical guide and printed titanium reconstruction plate in surgical transferring of virtual planning(7). In 2013, Simona Mazzoni and Leonardo Ciocca et al. applied the same surgical protocol in a study group of seven mandibular reconstruction patients and compared its advantages with the standard pre-plating technique on stereolithographic models in a control group. The results revealed the computer-aided surgical protocol was viable in reproducing the patients' anatomical contour, giving the surgeon better procedural control and reducing procedure time(8). In 2015, Simona Mazzoni et al. further developed the computer-aided designing and manufacturing technique in fabricating surgical cutting guides and titanium fixation plates in upper maxilla repositioning surgery without an occlusal wafer. The study result confirmed the high accuracy in transferring the virtual planning by using the surgical guides and fixation plates(9). In reviewing the literature, the application of 3D printing of titanium fixation plates in jaw surgery are available only at two centers currently: the Maxillofacial Surgery Department of S Orsola Malpighi Hospital in Italy and the Oral and Maxillofacial Surgery Department of Lund University in Sweden(6,7). The published preliminary work have proved the prospect of 3D-printed titanium plates in promoting mandibular reconstruction surgery and upper maxilla orthognathic surgery though their printed titanium plates looked rather bulky and the sample sizes were small and there is still lack of qualified randomized controlled trials between the printed and the conventional titanium plates. To better benefit from the burgeoning use of 3D printing in health care, we will develop a new designing and manufacturing protocol in printing customized fixation plates, which will be designed in specific loading circumstances and will perfectly adapt to the anatomical structures of the jaw. It is imperative to conduct a feasibility study in exploring the application of 3D printing of titanium fixation plates in jaw surgery based on our patients.

Official Title
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Three-Dimensional Printing of Patient-Specific Titanium Plates in Jaw Surgery: An Open-Label, Prospective Pilot Clinical Study

Conditions
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Mandibular Neoplasms, Maxillary Neoplasms, Dentofacial Deformities, Maxillofacial Injuries

Intervention / Treatment
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* Device: 3D-printed patient-specific titanium plates


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 18 of either gender; and Signed informed consent form;and Single or double-jaw orthognathic surgery under general anaesthesia, or Jaw reconstruction due to benign or malignant tumor, osteomyelitis, and osteonecrosis under general anaesthesia. Exclusion Criteria: Unstable or complicated systemic diseases that contraindicate the surgical process. Severe systemic diseases or conditions that would potentially compromise the healing process. Patients who are pregnant. Patients who are unable to take CT/CBCT scans.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open-label, prospective, single-arm, and single-center interventional clinical study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3D Jaw Plate<br>3D Jaw Plate will be used in internal fixation. | Device: 3D-printed patient-specific titanium plates<br>* 3D-printed patient-specific titanium plates will be used in patients.<br>* Other names: 3D Jaw Plate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative success rate | 1) the uneventful application of the 3D-printed patient-specific titanium plate in jaw surgery without any minor revision; 2) the final restored outcome being optimal based on clinical parameters. | Intraoperation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of postoperative adverse events [safety] | An adverse event is defined as any untoward medical occurrence in a patient administered the 3D-printed patient-specific titanium plate, which may or may not necessarily have a causal relationship with this new device. | 2-5 years postoperation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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3D printing, patient-specific titanium plate, mandibular malignancy, dento-maxillofacial deformity, orthognathic surgery, mandibular reconstruction