Corrosion of titanium dental implants has been associated with implant failure and is considered one of the triggering factors for peri-implantitis. This corrosion is concerning, because a large amount of metal ions and debris are generated in this process, the accumulation of which may lead to adverse tissue reactions in vivo. The goal of this study is to investigate the mechanisms for implant degradation by evaluating the surface of five titanium dental implants retrieved due to peri-implantitis. The results demonstrated that all the implants were subjected to very acidic environments, which, in combination with normal implant loading, led to cases of severe implant discoloration, pitting attack, cracking and fretting-crevice corrosion. The results suggest that acidic environments induced by bacterial biofilms and/or inflammatory processes may trigger oxidation of the surface of titanium dental implants. The corrosive process can lead to permanent breakdown of the oxide film, which, besides releasing metal ions and debris in vivo, may also hinder re-integration of the implant surface with surrounding bone.

At present, the exact mechanism for introduction of these materials and their role in peri-implantitis is unknown. Further research is warranted to determine their etiology and potential role in pathogenesis.

Titanium alloys are widely used in total-joint replacements due to a combination of outstanding mechanical properties, biocompatibility, passivity and corrosion resistance. Nevertheless, retrieval studies have pointed out that these materials can be subjected to localized or general corrosion in modular interfaces when mechanical abrasion of the oxide film (fretting) occurs. Modularity adds large crevice environments, which are subject to micromotion between contacting interfaces and differential aeration of the surface. Titanium alloys are also known to be susceptible to hydrogen absorption, which can induce precipitation of hydrides and subsequent brittle failure. In this work, the surface of three designs of retrieved hip-implants with Ti-6Al-4V/Ti-6Al-4V modular taper interfaces in the stem were investigated for evidence of severe corrosion and precipitation of brittle hydrides during fretting-crevice corrosion in the modular connections. The devices were retrieved from patients and studied by means of scanning electron microscopy (SEM), x-ray diffraction (XRD) and chemical analysis. The surface qualitative investigation revealed severe corrosion attack in the mating interfaces with evidence of etching, pitting, delamination and surface cracking. In vivo hydrogen embrittlement was shown to be a mechanism of degradation in modular connections resulting from electrochemical reactions induced in the crevice environment of the tapers during fretting-crevice corrosion.

It was demonstrated in this study that acidic environments coupled with rubbing are able to introduce noticeable morphological changes and corrosion on the surface of both titanium grades.

Despite the successful clinical application of titanium (Ti) as a biomaterial, the exact cellular and molecular mechanisms responsible for Ti osseointegration remains unclear, especially because of the limited methodological tools available in this field.Objective:In this study, we present a microscopic and molecular characterization of an oral implant osseointegration model using C57Bl/6 mice.Material and Methods:Forty-eight male wild-type mice received a Ti implant on the edentulous alveolar crest and the peri-implant sites were evaluated through microscopic (μCT, histological and birefringence) and molecular (RealTimePCRarray) analysis in different points in time after surgery (3, 7, 14 and 21 days).Results:The early stages of osseointegration were marked by an increased expression of growth factors and MSC markers. Subsequently, a provisional granulation tissue was formed, with high expression of VEGFb and earlier osteogenic markers (BMPs, ALP and Runx2). The immune/inflammatory phase was evidenced by an increased density of inflammatory cells, and high expression of cytokines (TNF, IL6, IL1) chemokines (CXCL3, CCL2, CCL5 and CXC3CL1) and chemokine receptors (CCR2 and CCR5). Also, iNOS expression remained low, while ARG1 was upregulated, indicating predominance of a M2-type response. At later points in time, the bone matrix density and volume were increased, in agreement with a high expression of Col1a1 and Col21a2. The remodelling process was marked by peaks of MMPs, RANKL and OPG expression at 14 days, and an increased density of osteoclasts. At 21 days, intimate Ti/bone contact was observed, with expression of final osteoblast differentiation markers (PHEX, SOST), as well as red spectrum collagen fibers.Conclusions:This study demonstrated a unique molecular view of oral osseointegration kinetics in C57Bl/6 mice, evidencing potential elements responsible for orchestrating cell migration, proliferation, ECM deposition and maturation, angiogenesis, bone formation and remodeling at the bone-implant interface in parallel with a novel microscopic analysis.

New dicationic imidazolium-based ionic liquids (ILs) were synthesized, characterized and tested in regards to cytotoxicity and antimicrobial activity. Insertion of a new cationic head and use of organic anions increased the biocompatibility of the ILs developed. IC 50 (concentration necessary to inhibit 50% of enzymatic activity) values obtained were considerably higher than those described for monocationic ILs, which indicates an improvement in cytocompatibility. Antimicrobial activity against bacterial species of clinical relevance in wounds and the oral environment was tested. The results showed that ILs were effective in inhibiting bacterial growth even below the minimum inhibitory concentration (MIC). It was observed that structural features that confer higher hydrophobicity to ILs decreased both the IC 50 and MIC simultaneously. However, it was possible to establish an equilibrium between those two effects, which gives the safe range of concentrations that ILs can be employed. The results demonstrated that the dicationic-imidazolium-based ILs synthesized may constitute a potent strategy for applications requiring non-toxic materials exhibiting antimicrobial activity.

The release of the prototypic DAMP High Mobility Group Box 1 (HMGB1) into extracellular environment and its binding to the Receptor for Advanced Glycation End Products (RAGE) has been described to trigger sterile inflammation and regulate healing outcome. However, their role on host response to Ti-based biomaterials and in the subsequent osseointegration remains unexplored. In this study, HMGB1 and RAGE inhibition in the Ti-mediated osseointegration were investigated in C57Bl/6 mice. C57Bl/6 mice received a Ti-device implantation (Ti-screw in the edentulous alveolar crest and a Ti-disc in the subcutaneous tissue) and were evaluated by microscopic (microCT [bone] and histology [bone and subcutaneous]) and molecular methods (ELISA, PCR array) during 3, 7, 14, and 21 days. Mice were divided into 4 groups: Control (no treatment); GZA (IP injection of Glycyrrhizic Acid for HMGB1 inhibition, 4 mg/Kg/day); RAP (IP injection of RAGE Antagonistic Peptide, 4 mg/Kg/day), and vehicle controls (1.5% DMSO solution for GZA and 0.9% saline solution for RAP); treatments were given at all experimental time points, starting 1 day before surgeries. HMGB1 was detected in the Ti-implantation sites, adsorbed to the screws/discs. In Control and vehicle groups, osseointegration was characterized by a slight inflammatory response at early time points, followed by a gradual bone apposition and matrix maturation at late time points. The inhibition of HMGB1 or RAGE impaired the osseointegration, affecting the dynamics of mineralized and organic bone matrix, and resulting in a foreign body reaction, with persistence of macrophages, necrotic bone, and foreign body giant cells until later time points. While Control samples were characterized by a balance between M1 and M2-type response in bone and subcutaneous sites of implantation, and also MSC markers, the inhibition of HMGB1 or RAGE caused a higher expression M1 markers and pro-inflammatory cytokines, as well chemokines and receptors for macrophage migration until later time points. In conclusion, HMGB1 and RAGE have a marked role in the osseointegration, evidenced by their influence on host inflammatory immune response, which includes macrophages migration and M1/M2 response, MSC markers expression, which collectively modulate bone matrix deposition and osseointegration outcome.

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