Rethinking Biomedical Titanium Alloy Design: A Review of Challenges from Biological and Manufacturing Perspectives.

Current biomedical titanium alloys have been repurposed from other industries, which has contributed to several biologically driven implant failure mechanisms. This review highlights the added value that may be gained by building an appreciation of implant biological responses at the onset of alloy design. Specifically, the fundamental mechanisms associated with immune response, angiogenesis, osseointegration and the potential threat of infection are discussed, including how elemental selection can modulate these pivotal systems. With a view to expedite inclusion of these interactions in alloy design criteria, methods to analyze these performance characteristics are also summarized. While machine learning techniques are being increasingly used to unearth complex relationships between alloying elements and material properties, much is still unknown about the correlation between composition and some bio-related properties. To bridge this gap, high-throughput methods are also reviewed to validate biological response along with cutting edge manufacturing approaches that may support rapid discovery. Taken together, this review encourages the alloy development community to rethink their approach to enable a new generation of biomedical implants intrinsically designed for a life in the body, including functionality to tackle biological challenges thereby offering improved patient outcomes.