Evaluation of the Safety, Feasibility, and Early Clinical Outcomes of Patient-Specific Bone Defect Implants Fabricated From Titanium Alloy (Ti-6Al-4V) Using 3D Printing Technology

The goal of this clinical trial is to evaluate the safety and feasibility of patient-specific bone defect implants fabricated from Ti-6Al-4V using 3D printing technology and to assess early clinical outcomes within the first 12 months following implantation of these customized devices. The main question it aims to answer is: "In patients with bone defects requiring surgical reconstruction, are patient-specific bone defect implants fabricated from titanium alloy (Ti-6Al-4V) using 3D printing technology - designed and produced at VinUni, safe and feasible for clinical use, and do they result in favorable early clinical outcomes within the first 12 months following implantation?"

Study Overview

• Status: Not yet recruiting
• Conditions: Bone Loss; Bone Defects
• Intervention / Treatment: Device: Patient-specific 3D-printed Ti-6Al-4V bone implant

Detailed Description

Bone defects resulting from trauma, tumor resection, infection, or congenital abnormalities represent a significant clinical burden in orthopedic and reconstructive surgery worldwide. Large or complex bone defects often lead to prolonged disability, functional impairment, and reduced quality of life if not appropriately treated. According to the World Health Organization (WHO), each year there are approximately 20-50 million non-fatal road traffic injuries globally, many of which are associated with fractures and segmental bone loss requiring surgical intervention.1 In addition, age-related musculoskeletal disorders such as osteoporosis, which affects an estimated 200 million people worldwide, further increase the incidence of bone defects and fracture-related complications.2 Epidemiological studies have shown that bone loss following tumor resection, severe trauma, or chronic infection remains a major challenge due to limited regenerative capacity and high mechanical demands at defect sites. Traditional reconstruction methods, including autologous and allogeneic bone grafting, although widely applied, are associated with several limitations such as donor-site morbidity, limited graft availability, risk of infection transmission, prolonged treatment time, and difficulty in achieving optimal anatomical reconstruction.3,4 As a result, bone reconstruction using artificial implantable materials has emerged as a promising therapeutic strategy. Among available options, artificial bone implants based on metallic biomaterials, particularly titanium alloys, have gained increasing attention due to their ability to provide immediate mechanical stability and support biological integration.5-7 Titanium and titanium-based alloys have been extensively used in clinical bone implantation for several decades and are recognized as among the most reliable materials for skeletal reconstruction.5,7 These materials have demonstrated favorable mechanical strength, corrosion resistance, and excellent biocompatibility, allowing long-term implantation in the human body. Titanium implants have been successfully applied in a wide range of clinical settings, including cranial and craniofacial reconstruction, limb and long bone defect replacement, spinal fixation, and dental implantation.5 Regulatory authorities such as the U.S. Food and Drug Administration (FDA) have approved the use of titanium alloys, including Ti-6Al-4V, for implantable medical devices based on accumulated evidence of safety and effectiveness.6 Furthermore, international standards such as ISO 5832 and ISO 10993, and also Vietnamese national standard clearly define requirements for chemical composition, mechanical properties, and biocompatibility testing of titanium alloys used in medical implants.8-10 Numerous international and domestic studies have consistently reported low toxicity, minimal inflammatory response, and good osseointegration associated with titanium-based implants, thereby confirming their clinical safety and suitability for bone defect reconstruction.5-7 In recent years, additive manufacturing, commonly referred to as three-dimensional (3D) printing, has emerged as a major technological advancement in the fabrication of titanium alloy implants. Conventional manufacturing methods, such as casting, forging, or machining, often face limitations in producing complex geometries and patient-specific designs, particularly for irregular or large bone defects.6 In contrast, 3D printing technologies, especially laser-based techniques such as selective laser melting or laser powder bed fusion, enable the precise fabrication of Ti-6Al-4V implants based on individual patient anatomy.11 Using preoperative imaging data from computed tomography or magnetic resonance imaging, personalized implants can be digitally designed to closely match defect morphology. 12-15 This high level of design accuracy allows improved implant fit, optimized load transmission, and the incorporation of porous or lattice structures that enhance bone ingrowth and biological fixation.9,11 Consequently, 3D-printed titanium implants offer significant advantages in addressing complex bone defects where conventional implants may be inadequate.

Globally, a growing number of studies have investigated the clinical application of 3D-printed titanium implants in bone defect reconstruction and have reported encouraging early outcomes. International case series and clinical reports have described successful use of patient-specific 3D-printed Ti-6Al-4V implants in pelvic reconstruction following tumor resection, craniofacial and cranial defect repair, limb-salvage surgery, and complex defects of the foot and ankle.16-19 These studies have demonstrated acceptable safety profiles, satisfactory implant stability, favorable bone integration, and improvement in functional outcomes during early follow-up periods. Reviews published in international orthopedic and biomaterials journals have emphasized the advantages of personalized implant design and porous surface architecture in promoting osseointegration and functional recovery.17 In Vietnam, research and clinical implementation of 3D printing technology in bone implantation are rapidly developing, with increasing application in craniofacial surgery, orthopedic trauma, and oncology.20 However, most domestic reports remain limited to technical descriptions or isolated clinical cases, and prospective clinical studies with standardized evaluation of safety and early outcomes are still scarce.

Despite the growing international experience and emerging clinical applications in Vietnam, several critical gaps remain that justify the necessity of this study. according to the latest guidelines from the Ministry of Health, as high-risk medical devices (Class D), patient-specific 3D-printed titanium implants are required to undergo systematic clinical evaluation across Phase I, II, and III trials to rigorously demonstrate safety, feasibility, and clinical effectiveness prior to widespread clinical implementation.21 Although preliminary studies in Vietnam have investigated similar products, most available evidence remains limited to isolated cases or technical reports, with a lack of prospective, systematically designed clinical studies.22 Furthermore, differences in manufacturing systems, machine configurations, material handling, and process parameters across production facilities may substantially influence implant quality and clinical performance, thereby necessitating site-specific clinical evidence to confirm that implants fabricated at a given 3D printing laboratory are safe, feasible, and effective in patients.23,24 This study is therefore essential to address these regulatory and scientific requirements and to generate foundational clinical evidence supporting responsible clinical translation of 3D-printed titanium implants. In this context, the 3D Medical Technology Laboratory at VinUniversity serves as a site-specific manufacturing facility for patient-specific 3D-printed implants, operating in compliance with internationally recognized ISO standards for medical device production and being entrusted by the Ministry of Health, particularly the Department of Science, Technology and Training, to support clinical evaluation activities.25 This study is therefore essential to address these regulatory and scientific requirements and to generate foundational clinical evidence supporting the responsible clinical translation of 3D-printed titanium implants produced within this manufacturing system.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Trung Dzung Tran, Professor, PhD, MD; Phone Number: +84983762005; Email: dung.tt@vinuni.edu.vn

Study Locations

• Vietnam
  • Hanoi, Vietnam, 100000
    • 3D Technology in Medicine Center (3D Lab, VinUni)
    • Contact: Trung Dung Tran, Professor, PhD, MD; Email: dung.tt@vinuni.edu.vn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with a bone defect requiring surgical reconstruction, as determined by the treating orthopedic surgeon
• Suitable candidate for implantation of a patient-specific device manufactured from Ti-6Al-4V
• Able to undergo preoperative imaging (CT ± MRI) required for implant design
• Willing and able to provide written informed consent
• Willing to comply with scheduled follow-up visits and study assessments

Exclusion Criteria:

• Active systemic or local infection at the surgical site at the time of implantation
• Known hypersensitivity or allergy to titanium or titanium alloys
• Severe uncontrolled comorbidities that significantly increase surgical risk (e.g., uncontrolled diabetes, severe cardiovascular disease)
• Pregnant or breastfeeding women
• Participation in another interventional clinical study that may interfere with the outcomes of this study
• Inability to complete follow-up assessments within the required timeframe

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patient-specific 3D-printed Ti-6Al-4V implant reconstruction; Participants in this arm will undergo surgical reconstruction of bone defects using patient-specific implants fabricated from titanium alloy (Ti-6Al-4V) through three-dimensional (3D) printing technology. Implants are designed based on preoperative imaging data (CT ± MRI) and manufactured using laser powder bed fusion/selective laser melting. The study evaluates the safety, feasibility, and early clinical outcomes of these customized implants during a 12-month follow-up period.

Device: Patient-specific 3D-printed Ti-6Al-4V bone implant; The investigational device is a patient-specific bone implant manufactured from titanium alloy Ti-6Al-4V using metal additive manufacturing technology. The implant is designed individually for each patient based on medical imaging data (CT or MRI), which are converted from DICOM format into three-dimensional digital models for anatomical reconstruction and implant design. The device is fabricated using selective laser melting (SLM) technology, in which high-power laser beams selectively fuse layers of Ti-6Al-4V powder to produce the final implant geometry. The manufacturing process is performed on a metal additive manufacturing system under an inert gas environment to prevent oxidation and ensure material integrity. Titanium powder feedstock complies with ASTM F2924 specifications for medical-grade Ti-6Al-4V used in powder bed fusion processes. Following printing, implants undergo standardized post-processing procedures including support removal, surface cleaning and finishing, stress-

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Major Postoperative Complications	Assessment of major postoperative complications related to the implant or surgical procedure (Yes/No), based on clinical examination and medical record review.	1-4 weeks postoperatively and from 6 weeks up to 12 months postoperatively
Number of Participants with Early Local Complications	Assessment of early local complications including wound discharge, bleeding, swelling, pain, and sensory disturbance, evaluated using standardized clinical examination.	Within 4 weeks postoperatively
Number of Participants with Early Systemic Complications	Assessment of early systemic complications including sepsis, hemodynamic instability, and respiratory failure, based on clinical evaluation and inpatient medical records.	Within 4 weeks postoperatively
Number of Participants with Late Implant-Related Complications	Assessment of late implant-related complications including implant loosening, sinus tract formation, and persistent pain, evaluated through clinical examination.	From 6 weeks up to 12 months postoperatively
Change in C-reactive Protein (CRP) Level	CRP levels (mg/L) will be measured using standard laboratory blood tests as an indicator of systemic inflammatory response following implantation.	Within 4 weeks postoperatively and from 6 weeks up to 12 months postoperatively
Change in White Blood Cell (WBC) Count	WBC count (×10⁹/L) will be measured using standard hematology tests as an indicator of infection or systemic inflammatory response.	Within 4 weeks postoperatively and from 6 weeks up to 12 months postoperatively
Operative Time	Duration of the surgical procedure measured in minutes, recorded from surgical records.	Intraoperative period
Estimated Blood Loss	Estimated intraoperative blood loss measured in milliliters (mL), recorded from surgical records.	Intraoperative period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Implant Stability (No Implant Loosening)	Assessment of implant stability defined as absence of implant loosening (Yes/No), evaluated by clinical examination and imaging (X-ray or CT).	At 3, 6, and 12 months postoperatively
Rate of Successful Bone-Implant Integration on Imaging	Assessment of osseointegration based on imaging findings (X-ray or CT), defined as absence of radiolucent lines and presence of a stable bone-implant interface.	At 3, 6, and 12 months postoperatively
Number of Participants with restoration of Anatomical Structure	Assessment of postoperative anatomical reconstruction (e.g., limb morphology) using clinical evaluation and imaging documentation.	Postoperative period and at 12 months postoperatively
Change in Pain Score Measured by Visual Analog Scale (VAS)	Pain intensity will be assessed using the Visual Analog Scale (VAS), a standardized 0-10 scale, with higher scores indicating greater pain.	Baseline and at 1, 3, 6, and 12 months postoperatively
Change in Functional Outcome Score	Functional outcomes will be assessed using validated patient-reported outcome measures, depending on the anatomical site of implantation: Upper extremity: Disabilities of the Arm, Shoulder and Hand (DASH) score (range: 0-100; higher scores indicate greater disability and worse function); Lower extremity: Lower Extremity Functional Scale (LEFS) (range: 0-80; higher scores indicate better functional status)	Baseline and at 3, 6, and 12 months postoperatively
Change in Health-Related Quality of Life (SF-36 Score)	Health-related quality of life will be assessed using the Short Form-36 Health Survey (SF-36), a validated patient-reported outcome measure. The SF-36 includes eight domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health), which are summarized into Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Scores range from 0 to 100, with higher scores indicating better health-related quality of life.	Baseline and at 12 months postoperatively
Number of Participants with Limb Length Discrepancy	Assessment of limb length discrepancy (Yes/No), evaluated using clinical examination and imaging.	From 6 weeks up to 12 months postoperatively

Collaborators and Investigators

• Sponsor: VinUniversity
• Collaborators: Vinmec Healthcare System

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 10, 2026
• First Submitted That Met QC Criteria: April 16, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Bone defect reconstruction; Three-dimensional (3D) printing; Patient-specific implants; Titanium alloy Ti-6Al-4V
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Bone Diseases, Metabolic
• Other Study ID Numbers: VINUNI-MD-2026-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No