Design of High Throughput Techniques for Functional Medical Devices

Since the early designs of medical devices, it has become apparent that implants should act as modulators of specific biological processes to ensure short- and long-term benefits¹. Nevertheless, standard alloys used in orthopaedics have been repurposed from other industries (e.g. aerospace) as a consequence of their mechanical behaviour, corrosion resistance and biocompatibility. With increased life expectancy requiring longer service life of implantable devices and common alloying elements (e.g. aluminium or vanadium) demonstrated to negatively impact biological processes beyond cytotoxicity, it is clear that novel medical alloys should be developed to modulate clinical outcomes^2. In this work, the difficulties of designing alloys for implantable devices will be contextualised, providing case studies focused on generating high throughput methods for their use in alloy development with especial attention on the advantages posed by metal additive manufacturing (AM) platforms.<br/><br/>When metallic elements are considered, there exist a plethora of materials with reported effects on biocompatibility, antimicrobial, angiogenic, osteogenic properties and/or their ability to modulate the innate and adaptive immune response^3. Nevertheless, most effects been reported for single element compounds, reducing their direct correlation to complex alloys and calling for methods to rapidly evaluate biological properties. The first case study will showcase the development of high throughput techniques for both material processing and biological evaluation. The use of AM and novel Reduce Build Volume designs for Powder Bed fusion coupled with powder blending will be shown as a tool to enable the rapid evaluation of alloy systems for antimicrobial applications with conventional and AM Ti-Cu samples used to highlight their benefits over traditional casting. Microstructural variations were assessed through SEM imaging, X-ray diffraction and Vickers microhardness evaluation which were complemented with antimicrobial assays in model strains of <i>S. aureus</i> and <i>P. aeruginosa</i>. In addition, the power of powder compaction and HIP technologies will be harnessed to enable the rapid analysis of bacterial behaviour and antibiotic synergistic/antagonistic effects through the agar diffuse method and metabolic assays in model strains of Gram-positive and Gram-negative species to enable novel databases in the healthcare industry.<br/><br/>Besides combinations of different metallic elements, alloy design should consider the effect of microstructure and the manufacturing of complex alloys with significantly different processing parameters. Copper and Molybdenum are two elements that have shown promise to tackle antibiotic infection, nevertheless, their disparity in reflectivity or melting point has made their incorporation in titanium alloys a challenge from a manufacturing perspective. Herein, the use of AM, powder compaction and sintering will be used to demonstrate the possibility of providing novel alloys with highly different elemental properties and their use in multicomponent alloys. Through variations in composition and heat treatment, we successfully produced a blended powder of two dissimilar elements which can be used to manufacture SLM parts with reduced input energies (133J/m instead of 300J/m)⁴. Similarly, the effect of microstructural variations with antimicrobial properties and eukaryotic cell line responses will be shown for the rapid optimisation of novel alloys.<br/><br/><b>REFERENCES</b><br/>[1] D.F. Williams, Bioactive Materials, 10, 306-322 (2022) [2] R.P. Brown, et al. In Toxicology of Metals, Academic Press, 127-136 (2022) [3] K. Glenske, et al. International journal of molecular sciences, 19, 826 (2018) [4] R. Duan, et al. Composites Part B: Engineering, 222, 109059 (2021)