Inflammatory or Reparative? Tuning Macrophage Polarization Using Anodized Anisotropic Nanoporous Titanium Implant Surfaces

Abstract

Modulating macrophage phenotype based on implant surface characteristics, including topography and chemistry, has been employed to enhance osseointegration and long-term functional outcomes for titanium (Ti)-based implants. An excessive and/or prolonged M1 macrophage response can lead to damaging immune-inflammatory reactions, negatively influencing the fate of the implant, and hence, modulating these responses via nanoscale implant surface modification is an emerging paradigm. Herein, an anodized titanium implant surface based on single-step electrochemical anodization, with preserved underlying microfeatures and superimposed nanopores (50 and 70 nm), compared with irregular rough and microrough (machined-like) surfaces, is investigated for its effect on the functions of primary macrophages in vitro. Significantly reduced macrophage proliferation and increased tissue-reparative M2 phenotype polarization are confirmed for the nanopores, which are more pronounced for 70 nm diameter. Moreover, osteoclastogenesis is reduced while osteogenic differentiation of osteoblasts is enhanced for the nanopores (higher for 70 nm pores). Advanced nanoengineered Ti implants can enhance titanium implant tissue integration by modulating the inflammatory response at the implant–cell interface.