Antibacterial alloys: development by additive 3D manufacturing, characterization and clinical applications

Population ageing presents an extraordinary challenge for society. Treatments of age-related diseases like osteoarthritis and dental conditions are increasing accordingly. Around 1.5 million orthopaedic and 5.5 million dental implants are implanted annually in the EU. But even when the implant materials are appropriately selected, and the surgical technique is highly efficient, the implant may fail due to the implant-related infection (IRI). IRI is the most severe complication of reconstruction surgery, which requires long-term antibiotic treatment, implant replacement, and sometimes amputation. Prosthetic joint infections have similar mortality as some common cancers. The impacts on the healthcare systems are enormous. Therefore, it is in great interest primarily for the patients, the medical community, and the national health budget to keep the infection incidence low - either by improving antibiotic prophylaxis or by using the innovative materials to prevent IRI. The current clinical practice does not include materials able to fight against infection and relies on antibiotics and implant explantation. Abundant antibiotic consumption is leading to antimicrobial resistance. This project aims to combat implant infection by taking a different strategy, namely, by developing a new class of antibacterial alloys for implants with inherent long-term antibacterial activity. Antibacterial alloys will eliminate the need for surface modifications or coatings, which have still not entered the clinical phase although being vividly researched academically. The work programme is divided into two parts. In the CLINICAL part, retrospective and prospective studies on the infection incidence and factor analysis will be performed for orthopaedic and dental implants. Healthcare clinical guidelines on IRI will be postulated. In parallel, clinical samples will be collected and analyzed microbiologically. In the EXPERIMENTAL part, we will start from the most crucial commercial implant material, Ti-6Al-4V alloy, and intend to add copper, as a known antimicrobial agent and an essential element in the human body, to obtain Ti-6Al-4V-xCu alloys, where x is the content of copper. This new material will be developed using a novel technology of additive 3D manufacturing and selected post-treatments to tailor the materials and design properties. Materials characterization in terms of mechanical, materials, corrosion, Cu release, in vitro osteointegration, antibacterial and biocompatibility properties will be carried out. Finally, animal in vivo testing of selected samples will be performed as a final, preclinical step. Scientific challenges include developing the Ti-6Al-4V-xCu alloy with optimized content of Cu, appropriate microstructure, minimum porosity and defined roughness, suitable mechanical properties, high corrosion resistance, antibacterial activity against relevant clinical bacteria strains and biocompatibility. Project results will be significant for the medical community, technology and materials development and natural science. Most importantly, the gain of new material could result in alleviating of patients’ suffering due to IRI. Project partners form a consortium that is capable of establishing antibacterial alloys as a new strategy of combating IRI. They are experts from various disciplines: orthopaedic surgery (VOH) and dental implantology (FM UL), technology development (FME UL), materials and corrosion science (JSI), microbiology, biocompatibility, antibacterial treatments, implant lifetime statistics (VOH) and animal experiments (BF UL). The project covers a whole cycle starting from the clinical needs and expertise in medicine over technology development and materials characterization, antibacterial and biocompatibility assessment up to animal testing as a preclinical phase. The project will also open new possibilities for a broad spectrum of applications in medicine and biotechnology.