Titanium micro-nano texturized surface with strontium incorporation improves osseointegration. An in vivo and in vitro study.

Abstract

Abstract Objectives: This study aimed to investigate the osseointegration of titanium (Ti) implants with micro-nanotextured surfaces functionalized with strontium additions (Sr) in a pre-clinical rat tibia model. Materials and Methods: Ti commercially pure (cp-Ti) implants were installed bilaterally on the tibia of 64 Holtzman rats, divided into four experimental groups (n=16/group): (1) Machined surface - control (C group); (2) Micro-nano textured surface treatment (MN group); (3) Micro-nano textured surface with Sr2+ addition (group MNSr); (4) Micro-nano textured surface with a higher complementary addition of Sr2+ (MNSr+). Two experimental euthanasia periods were assessed at 15 and 45 days (n=8/period). The tibia was subjected to micro-computed tomography (μ-CT), histomorphometry with the EXAKT system, removal torque (TR) testing, and gene expression analysis by PCR-Array of 84 osteogenic markers. Gene expression and protein production of bone markers were performed in an in vitro model with MC3T3-E1 cells. The surface characteristics of the implants were evaluated by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and laser scanning confocal microscopy. Results: SEM, confocal, and EDS analyses demonstrated the formation of uniform micro-nano textured surfaces in the MN group and Sr addition in the MNSr and MNSr+ groups. The removal torque (TR) test indicated greater osseointegration in the later period for treated surfaces. Histological analysis highlighted the benefits of the treatments, especially in cortical bone, where there was an increase in bone-implant contact in groups MN (15 days) and MNSr (45 days) compared to the control group. Micro-CT revealed similar trends to histological analyses, although they did not reach statistical significance between the treatment groups and the control group. Gene expression analysis of osteogenic activity markers showed modulation of various genes related to osteogenesis. According to the in vitro model, RT-qPCR and ELISA demonstrated that the treatments favored gene expression and production of osteoblastic differentiation and activity markers. Conclusions: Our results demonstrated that the micro-nano textured surface and Sr addition may be effective in improving and accelerating the implant osseointegration in cortical and cancellous bone, resulting in increased osseointegration. This makes this approach an attractive option for modifying titanium implant surfaces with significant potential in clinical practice. Clinical relevance: Subsequent advancements in the design and composition of dental implant surfaces are deemed pivotal to enhance osseointegration. This is a pre-clinical study in an animal model that evaluated the behavior of new strontium-doped surfaces. The results showed that doped titanium surfaces with Sr can improve osseointegration events, highlighting the potential use of Sr surfaces to improve results in complex clinical scenarios.