Rational design, bio-functionalization and biological performance of hybrid additive manufactured titanium implants for orthopaedic applications: A review.

Evolution of metallurgy and biomaterials has progressively shifted the focus of metallic bone-interfacing implant design from adequate mechanical strength and biocompatibility to rapid osseointegration and infection inhibition. The now relatively well-established technology - powder bed additive manufacturing (AM), offers the ability to fabricate porous implants with precise mechanical properties, topological pore architectures and patient-specific design functions, has revolutionized the production of customized multifunctional metallic implants for the individual patient with anatomic-specific requirement. Even though AM titanium and its alloy Ti-6Al-4V have been investigated and adopted for clinical application for decades, the development of porous AM titanium implants is far from complete and further research is required to achieve excellent long-term clinical performance. In this review, we summarize the current status of AM in bone-interfacing implant fabrication, with particular focus on the experimental outcomes of various factors that influence osseointegration, bone and vascular ingrowth as well as hybrid strategies to combat infection, including: pore size, porosity, pore structure, surface modification techniques and incorporation of biological factors. In addition, we also discuss the osteogenic capacity of constructs fabricated through different manufacturing methods and titanium alloys. To this end, we highlight the exciting prospect of AM for bone-interfacing implant manufacture through optimization via material development, implant design, bio-functionalization to clinical evaluation to provide enhanced patient specificity and long-term function.