Nanointeraction: The profound influence of nanostructured and nano-drug delivery biomedical implant surfaces on cell behavior.

Nanostructured surfaces feature promising biological properties on biomaterials attracting large interest at basic research, implant industry development, and bioengineering applications. Thou, nanoscale interactions at a molecular and cellular level are not yet completely understood and its biological and clinical implications need to be further elucidated. As follows, the aim of this comprehensive review was to evaluate nanostructured surfaces at biomedical implants focusing on surface development, nanostructuration, and nanoengineered drug delivery systems that can induce specific cell interactions in all relevant aspects of biological, reparative, anti-bacterial, anti-inflammatory and clinical processes. The methods and the physio-chemical properties involved in nanotopography performance, the main cellular characteristics involved at surface/cell interaction, and a summary of results and outlooks reported in studies applying nanostructured surfaces and nano-drug delivery systems is presented. The future prospects and commercial translation of this developing field, particularly concerning multifunctional nanostructured surfaces and its clinical implications are further discussed. At a cellular level, nanostructured biomedical implant surfaces can enhance osteogenesis by targeting osteoblasts, osteocytes, and mesenchymal cells, stimulate fibroblast/epithelial cells proliferation and adherence, inhibit bacterial cell proliferation and biofilm accumulation, and act as immune-modulating surfaces targeting macrophages and reducing pro-inflammatory cytokine expression. Moreover, several methodological options to create drug-delivery systems on metallic implant surfaces are available, however, the clinical translation is yet incomplete. The efficiency of which nanostructured/nano-delivery surfaces may target specific cell interactions and favor clinical outcomes needs to be further elucidated in pre-clinical and clinical studies, along with engineering solutions for commercial translation and approval of controlling agencies.