Local and Systemic In Vivo Responses to Osseointegrative Titanium Nanotube Surfaces

Abstract

Orthopedic implants requiring osseointegration are often surface modified; however, implants may shed these coatings and generate wear debris leading to complications. Titanium nanotubes (TiNT), a new surface treatment, may promote osseointegration. In this study, in vitro (rat marrow-derived bone marrow cell attachment and morphology) and in vivo (rat model of intramedullary fixation) experiments characterized local and systemic responses of two TiNT surface morphologies, aligned and trabecular, via animal and remote organ weight, metal ion, hematologic, and nondecalcified histologic analyses. In vitro experiments showed total adherent cells on trabecular and aligned TiNT surfaces were greater than control at 30 min and 4 h, and cells were smaller in diameter and more eccentric. Control animals gained more weight, on average; however, no animals met the institutional trigger for weight loss. No hematologic parameters (complete blood count with differential) were significantly different for TiNT groups vs. control. Inductively coupled plasma mass spectrometry (ICP-MS) showed greater aluminum levels in the lungs of the trabecular TiNT group than in those of the controls. Histologic analysis demonstrated no inflammatory infiltrate, cytotoxic, or necrotic conditions in proximity of K-wires. There were significantly fewer eosinophils/basophils and neutrophils in the distal region of trabecular TiNT-implanted femora; and, in the midshaft of aligned TiNT-implanted femora, there were significantly fewer foreign body giant/multinucleated cells and neutrophils, indicating a decreased immune response in aligned TiNT-implanted femora compared to controls.