Profiling to Probing: Atomic force microscopy to characterize nano-engineered implants

Surface modification of implants in the nanoscale or implant nano-engineering has been recognized as a strategy for augmenting implant bioactivity and achieving long-term implant success. Characterizing and optimizing implant characteristics is crucial to achieve desirable effects post-implantation. Modified implant enables tailored, guided and accelerated tissue integration; however, our understanding is limited to multicellular (bulk) interactions. Finding the nanoscale forces experienced by a single cell on nano-engineered implants will aid in predicting implants' bioactivity via precise quantification of adhesive forces between a cell and the modified implant surface and engineering the next generation of bioactive implants. Atomic force microscope (AFM) is a unique tool that enables surface characterization and understanding of the interactions between implant surface and biological tissues, aiding in understanding implant-tissue interactions and bioactivity. The characterization of surface topography using AFM to gauge nano-engineered implants' characteristics (topographical, mechanical, chemical, electrical and magnetic) and bioactivity (adhesion of cells) is presented. A special focus of the review is to discuss the use of single-cell force spectroscopy (SCFS) employing AFM to investigate the minute forces involved with the adhesion of a single cell (resident tissue cell or bacterium) to the surface of nano-engineered implants. Finally, the research gaps and future perspectives relating to AFM-characterized current and emerging nano-engineered implants are discussed towards achieving desirable bioactivity performances. This review highlights the use of advanced AFM-based characterization of nano-engineered implant surfaces via profiling (investigating implant topography) or probing (using a single cell as a probe to study precise adhesive forces with the implant surface). Nano-engineering is emerging as a surface modification platform for implants to augment their bioactivity and achieve favourable treatment outcomes. In this extensive review, we closely examine the use of Atomic Force Microscopy (AFM) to characterize the properties of nano-engineered implant surfaces (topography, mechanical, chemical, electrical and magnetic). Next, we discuss Single-Cell Force Spectroscopy (SCFS) via AFM towards precise force quantification encompassing a single cell's interaction with the implant surface. This interdisciplinary review will appeal to researchers from the broader scientific community interested in implants and cell adhesion to implants and provide an improved understanding of the surface characterization of nano-engineered implants.