Nano-engineering the titanium-tissue interface: a 15 year perspective on bio-functionalization and surface innovation

Biofunctionalization of nanostructured titanium surfaces is a promising strategy to improve the performance of biomedical implants and devices. While titanium offers excellent mechanical properties and biocompatibility, it often encounters challenges such as bacterial infections, thrombogenicity, and complex cellular interactions. This review highlights decades of research in our laboratory on surface nanoengineering and biomaterial coating innovations that have significantly enhanced cellular adhesion, growth, and differentiation. Nanoengineered surfaces with adjustable wettability can significantly impact protein adsorption, cell adhesion, and blood compatibility. The potential of various biopolymer coatings, such as tanfloc, chitosan, heparin, and multilayer polyelectrolyte combinations, to promote beneficial cellular responses, support stem cell differentiation, and enhance hemocompatibility is also examined. Furthermore, the antimicrobial effects of these biopolymer-coated nanostructured titanium surfaces show promise in reducing infection risks associated with implants. Additionally, integrating small biomolecules, growth factors, and mineralization processes with relevant active metal ions reveals the potential of combining surface functionalization with nanoalteration. Finally, the review discusses current challenges and prospects in titanium implant surface engineering, underscoring the importance of further research to refine these technologies for therapeutic applications.