Precision Surface Engineering of Metallic Biomaterials: Translating Cell-Instructive Nanoscale Topographies from Bench to Bone-Interfacing Implants

Abstract

Metallic biomaterials remain foundational to orthopedic, spinal and dental implants owing to their mechanical properties, corrosion resistance and biocompatibility. Yet, unsatisfactory osseointegration and implant failure persist, often driven by limited stability, poor bone quality and dysregulated host immune responses. Over the past two decades, nanoscale surface engineering has consolidated its role as a powerful strategy to tune early cell-material interactions and downstream tissue remodeling, with compelling evidence that nanotopographical features regulate cell-and tissue-level functions. Despite a large mechanistic and preclinical literature, clinical translation of cell-instructive nanotopographies remains constrained by manufacturing scalability on complex 3D implant geometries, metrological and process reproducibility, and an enduring in vitro-in vivo disconnect driven by factors such as simplified test systems, dynamic protein adsorption phenomena and interspecies variability, among others. In this perspective, we examine precision nanoscale topographical control as a design variable for bone-interfacing metallic implants and synthesize advances in top-down and bottom-up nanofabrication routes, from deterministic lithographies to scalable anodization and laser texturing. We critically evaluate preclinical model systems spanning 2D assays, 3D and microphysiological platforms, ex vivo tissues and animal studies, emphasizing how model selection shapes mechanistic inference and translational predictability. Finally, we discuss potential pathways toward clinical adoption to enable next-generation implant surfaces that deliver effective osseointegration and long-term clinical performance.