Micro/Nanostructured Topography on Titanium Orchestrates Dendritic Cell Adhesion and Activation via [beta]2 Integrin-FAK Signals

Background and Purpose: In clinical application of dental implants, the functional state of dendritic cells (DCs) has been suggested to have a close relationship with the implant survival rate or speed of osseointegration. Although microscale surfaces have a stable osteogenesis property, they also incline to trigger unfavorable DCs activation and threaten the osseointegration process. Nanoscale structures have an advantage in regulating cell immune response through orchestrating cell adhesion, indicating the potential of hierarchical micro/nanostructured surface in regulation of DCs' activation without sacrificing the advantage of microscale topography. Materials and Methods: Two micro/nanostructures were fabricated based on microscale rough surfaces through anodization or alkali treatment, the sand-blasted and acid-etched (SA) surface served as control. The surface characteristics, in vitro and in vivo DC immune reactions and [beta]2 integrin-FAK signal expression were systematically investigated. The DC responses to different surface topographies after FAK inhibition were also tested. Results: Both micro/nano-modified surfaces exhibited unique composite structures, with higher hydrophilicity and lower roughness compared to the SA surface. The DCs showed relatively immature functional states with round morphologies and significantly downregulated [beta]2 integrin-FAK levels on micro/nanostructures. Implant surfaces with micro/nano-topographies also triggered lower levels of DC inflammatory responses than SA surfaces in vivo. The inhibited FAK activation effectively reduced the differences in topography-caused DC activation and narrowed the differences in DC activation among the three groups. Conclusion: Compared to the SA surface with solely micro-scale topography, titanium surfaces with hybrid micro/nano-topographies reduced DC inflammatory response by influencing their adhesion states. This regulatory effect was accompanied by the modulation of [beta]2 integrin-FAK signal expression. The [beta]2 integrin-FAK-mediated adhesion plays a critical role in topography-induced DC activation, which represents a potential target for material-cell interaction regulation. Keywords: micro/nanostructure, dendritic cell, osteoimmunology, [beta]2 integrin-FAK signal, surface modification