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

Overview

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?"

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.