Implant surface modifications and their impact on osseointegration and peri-implant diseases through epigenetic changes: A scoping review.

Dental implant surfaces and their unique properties can interact with the surrounding oral tissues through epigenetic cues. The present scoping review provides current perspectives on surface modifications of dental implants, their impact on the osseointegration process, and the interaction between implant surface properties and epigenetics, also in peri-implant diseases. Findings of this review demonstrate the impact of innovative surface treatments on the epigenetic mechanisms of cells, showing promising results in the early stages of osseointegration. Dental implant surfaces with properties of hydrophilicity, nanotexturization, multifunctional coatings, and incorporated drug-release systems have demonstrated favorable outcomes for early bone adhesion, increased antibacterial features, and improved osseointegration. The interaction between modified surface morphologies, different chemical surface energies, and/or release of molecules within the oral tissues has been shown to influence epigenetic mechanisms of the surrounding tissues caused by a physical-chemical interaction. Epigenetic changes around dental implants in the state of health and disease are different. In conclusion, emerging approaches in surface modifications for dental implants functionalized with epigenetics have great potential with a significant impact on modulating bone healing during osseointegration.

TiO2 nanotubes as an antibacterial nanotextured surface for dental implants: Systematic review and meta-analysis.

OBJECTIVES: Nanotechnology is constantly advancing in dental science, progressing several features aimed at improving dental implants. An alternative for surface treatment of dental implants is electrochemical anodization, which may generate a nanotubular surface (TiO2 nanotubes) with antibacterial potential and osteoinductive features. This systematic review and meta-analysis aims to elucidate the possible antibacterial properties of the surface in question compared to the untreated titanium surface. SOURCES: For that purpose, was performed a systematic search on the bases PubMed, Lilacs, Embase, Web Of Science, Cinahl, and Cochrane Central, as well as, manual searches and gray literature. STUDY SELECTION: The searches resulted in 742 articles, of which 156 followed for full-text reading. Then, 37 were included in the systematic review and 8 were included in meta-analysis. RESULTS: Fifteen studies revealed significant antibacterial protection using TiO2 nanotube surfaces, while 15 studies found no statistical difference between control and nanotextured surfaces. Meta-analysis of in vitro studies demonstrated relevant bacterial reduction only for studies investigating Staphylococcus aureus in a period of 6 h. Meta-analysis of in vivo studies revealed three times lower bacterial adhesion and proliferation on TiO2 nanotube surfaces. CONCLUSIONS: TiO2 nanotube topography as a surface for dental implants in preclinical research has demonstrated a positive relationship with antibacterial properties, nevertheless, factors such as anodization protocols, bacteria strains, and mono-culture methods should be taken into consideration, consequently, further studies are necessary to promote clinical translatability.

Unveiling the consequences of early human saliva contamination on membranes for guided bone regeneration.

AIMS: GBR membranes have various surface properties designed to elicit positive responses in regenerative clinical procedures; dental clinicians attempt to employ techniques to prevent the direct interaction of contaminated oral fluids with these biomaterials. However, saliva is uninterruptedly exhibited in oral surgical procedures applying GBR membranes, suggesting a persistent interaction with biomaterials and the surrounding oral tissues. This fundamental study aimed to investigate potential alterations in the physical, chemical, and key biological properties of membranes for guided bone regeneration (GBR) caused by isolated early interaction with human saliva. METHODS: A reproducible step-by-step protocol for collecting and interacting human saliva with membranes was developed. Subsequently, membranes were evaluated for their physicochemical properties, protein quantification, DNA, and 16S rRNA levels viability of two different cell lines at 1 and 7 days, and ALP activity. Non-interacted membranes and pure saliva of donors were applied as controls. RESULTS: Qualitative morphological alterations were noticed; DNA extraction and 16S quantification revealed significantly higher values. Furthermore, the viability of HGF-1 and MC3T3-E1 cells was significantly (p < .05) reduced following saliva interaction with biodegradable membranes. Saliva contamination did not prejudice PTFE membranes significantly in any biological assay. CONCLUSIONS: These outcomes demonstrated a susceptible response of biodegradable membranes to isolated early human saliva interaction, suggesting impairment of structural morphology, reduced viability to HGF-1 and MC3T3-E1, and higher absorption/adherence of DNA/16S rRNA. As a result, clinical oral procedures may need corresponding refinements.

Trans-mucosal platforms for dental implants: Strategies to induce muco-integration and shield peri-implant diseases.

OBJECTIVES: Trans-mucosal platforms connecting the bone-anchored implants to the prosthetic teeth are essential for the success of oral rehabilitation in implant dentistry. This region promotes a challenging environment for the successfulness of dental components due to the transitional characteristics between soft and hard tissues, the presence of bacteria, and mechanical forces. This review explored the most current approaches to modify trans-mucosal components in terms of macro-design and surface properties. METHODS: This critical review article revised intensely the literature until July 2023 to demonstrate, discuss, and summarize the current knowledge about marketable and innovative trans-mucosal components for dental implants. RESULTS: A large number of dental implant brands have promoted the development of several implant-abutment designs in the clinical market. The progress of abutment designs shows an optimistic reduction of bacteria colonization underlying the implant-abutment gap, although, not completely inhibited. Fundamental and preclinical studies have demonstrated promising outcomes for altered-surface properties targeting antibacterial properties and soft tissue sealing. Nanotopographies, biomimetic coatings, and antibiotic-release properties have been shown to be able to modulate, align, orient soft tissue cells, and induce a reduction in biofilm formation, suggesting superior abilities compared to the current trans-mucosal platforms available on the market. SIGNIFICANCE: Future clinical implant-abutments show the possibility to reduce peri-implant diseases and fortify soft tissue interaction with the implant-substrate, defending the implant system from bacteria invasion. However, the absence of technologies translated to commercial stages reveals the need for findings to "bridge the gap" between scientific evidences published and applied science in the industry.

Nano-scaled surfaces and sustainable-antibiotic-release from polymeric coating for application on intra-osseous implants and trans-mucosal abutments.

Multifunctional surfaces may display the potential to accelerate and promote the healing process around dental implants. However, the initial cellular biocompatibility, molecular activity, and the release of functionalized molecules from these novel surfaces require extensive investigation for clinical use. Aiming to develop and compare innovative surfaces for application in dental implants, the present study utilized titanium disks, which were treated and divided into four groups: machined (Macro); acid-etched (Micro); anodized-hydrophilic surface (TNTs); and anodized surface coated with a rifampicin-loaded polymeric layer (poly(lactide-co-glycolide), PLGA) (TNTsRIMP). The samples were characterized regarding their physicochemical properties and the cumulative release of rifampicin (RIMP), investigated at different pH values. Additionally, differentiated osteoblasts from mesenchymal cells were used for cell viability and qRT-PCR analysis. Antibacterial properties of each surface treatment were investigated against Staphylococcus epidermidis. TNTsRIMP demonstrated controlled drug release for up to 7 days in neutral pH environments. Osteogenic cell cultures indicated that all the evaluated surfaces showed biocompatibility. The TNTs group revealed up-regulated values for bone-related gene quantification in 7 days, followed by the TNTsRIMP group. Furthermore, the antibiotic-functionalized surface revealed effectiveness to inhibit S. epidermidis and stimulate promising conditions for osteogenic cell behavior. Characteristics such as nanomorphology and hydrophilicity were determinants for the up-regulated quantification of osteogenic biomarkers related to early bone maturation, encouraging application in intra-osseous implant surfaces; in addition, antibiotic-functionalized surfaces demonstrated significant higher antibacterial properties compared to the other groups. Our findings suggest that polymeric-antibiotic-loaded coating might be applied for the prevention of early infections, favoring its application in multifunctional surfaces for intra- and/or trans-mucosal components of dental implants, while, hydrophilic nanotextured surfaces promoted optimistic properties to stimulate early bone-related cell responses, favoring its application in bone-anchored surfaces.

Does saliva contamination interfere or stimulate regenerative processes applying current biomaterials on oral surgical sites?

Innovative dental biomaterials have been developed in order to stimulate higher biocompatibility and faster healing times using responsive surfaces for regenerative procedures. However, saliva is one of the fluids to interact with these biomaterials in the first instance. Studies have revealed significant negative effects on the biomaterials' properties, biocompatibility and bacterial colonisation after saliva contact. Nevertheless, the current literature is unclear about the profound effects of saliva on regenerative procedures. The scientific community urges further detailed studies associating innovative biomaterials/saliva/microbiology/immunology in order to clarify clinical outcomes. This paper discusses and provides information about the challenges of research using human saliva, the lack of standardisation in protocols applying saliva, and tentative applications of saliva proteins associated with innovative dental biomaterials.

Bench-to-bedside: Feasibility of nano-engineered and drug-delivery biomaterials for bone-anchored implants and periodontal applications.

Nanotechnology and drug-release biomaterials have been thoroughly explored in the last few years aiming to develop specialized clinical treatments. However, it is rare to find biomaterials associated with drug delivery properties in the current dental market for application in oral bone- and periodontal-related procedures. The gap between basic scientific evidence and translation to a commercial product remains wide. Several challenges have been reported regarding the clinical translation of biomaterials with drug-delivery systems (BDDS) and nanofeatures. Therefore, processes for BDDS development, application in preclinical models, drug delivery doses, sterilization processes, storage protocols and approval requirements were explored in this review, associated with tentative solutions for these issues. The diversity of techniques and compounds/molecules applied to develop BDDS demands a case-by-case approach to manufacturing and validating a commercial biomaterial. Promising outcomes such as accelerated tissue healing and higher antibacterial response have been shown through basic and preclinical studies using BDDS and nano-engineered biomaterials; however, the adequate process for sterilization, storage, cost-effectiveness and possible cytotoxic effects remains unclear for multifunctional biomaterials incorporated with different chemical compounds; then BDDSs are rarely translated into products. The future benefits of BDDS and nano-engineered biomaterials have been reported suggesting personalized clinical treatment and a promising reduction in the use of systemic antibiotics. Finally, the launch of these specialized biomaterials with solid data and controlled traceability onto the market will generate strong specificity for healthcare treatments.

Guided bone regeneration in implant dentistry: Basic principle, progress over 35 years, and recent research activities.

Bone augmentation procedures are frequent today in implant patients, since an implant should be circumferentially anchored in bone at completion of bone healing to have a good long-term stability. The best documented surgical technique to achieve this goal is guided bone regeneration (GBR) utilizing barrier membranes in combination with bone fillers. This clinical review paper reflects 35 years of development and progress with GBR. In the 1990s, GBR was developed by defining the indications for GBR, examining various barrier membranes, bone grafts, and bone substitutes. Complications were identified and reduced by modifications of the surgical technique. Today, the selection criteria for various surgical approaches are much better understood, in particular, in post-extraction implant placement. In the majority of patients, biodegradable collagen membranes are used, mainly for horizontal bone augmentation, whereas bioinert PTFE membranes are preferred for vertical ridge augmentation. The leading surgeons are using a composite graft with autogenous bone chips to accelerate bone formation, in combination with a low-substitution bone filer to better maintain the augmented bone volume over time. In addition, major efforts have been made since the millenium change to reduce surgical trauma and patient morbidity as much as possible. At the end, some open questions related to GBR are discussed.

The Role of Titanium Particles and Ions in the Pathogenesis of Peri-Implantitis.

Titanium (Ti) particles and ions have been investigated in recent years as important factors in the pathogenesis of peri-implantitis. However, their role in the pathogenesis is yet to be fully understood. A review of pertinent literature was performed in various databases to determine the current position of Ti particles and ions role in the pathogenesis of peri-implantitis. There are several in vitro, preclinical and clinical published studies that have addressed the role of Ti particles and ions in the pathogenesis of peri-implantitis. These studies explored the effect of Ti particles and ions in the pathogenesis of peri-implantitis with respect to foreign body reaction, cellular response, epigenetic mechanisms, namely DNA methylation, and the oral microbiome. Studies have shown that the release of Ti particles/ions during implant insertion, early healing stages, late healing stages, and treatments during peri-implantitis might contribute to peri-implantitis through different mechanisms, such as foreign body reaction, cellular response, DNA methylation, and shaping the oral microbiome by increasing dysbiosis. However, further studies are needed to elucidate the complex interactions between all these mechanisms and Ti particles/ions in the pathogenesis and progression of peri-implantitis.

Superhydrophilic Nanotextured Surfaces for Dental Implants: Influence of Early Saliva Contamination and Wet Storage.

Hydrophilic and nanotextured surfaces for dental implants have been reported as relevant properties for early osseointegration. However, these surface characteristics are quite sensitive to oral interactions. Therefore, this pilot study aimed to investigate the superficial alterations caused on hydrophilic nanotubular surfaces after early human saliva interaction. Titanium disks were treated using an anodization protocol followed by reactive plasma application in order to achieve nanotopography and hydrophilicity, additionally; surfaces were stored in normal atmospheric oxygen or wet conditioning. Following, samples were interacted with saliva for 10 min and analyzed regarding physical-chemical properties and cellular viability. Saliva interaction did not show any significant influence on morphological characteristics, roughness measurements and chemical composition; however, hydrophilicity was statistically altered compromising this feature when the samples were stored in common air. Cellular viability tested with pre-osteoblasts cell line (MC3T3-E1) reduced significantly at 48 h on the samples without wet storage after saliva contamination. The applied wet-storage methodology appears to be effective in maintaining properties such as hydrophilicity during saliva interaction. In conclusion, saliva contamination might impair important properties of hydrophilic nanotubular surfaces when not stored in wet conditions, suggesting the need of saliva-controlled sites for oral application of hydrophilic surfaces and/or the use of modified-package methods associated with their wet storage.

Complete oral rehabilitation with direct and indirect composite resins: a minimally invasive approach on severely compromised teeth.

The rehabilitation of severely worn teeth is a complex challenge for dental practitioners. There are many different types of dental materials and restorative techniques, and there is not a single way to achieve the desired result. This clinical report demonstrates a complete oral rehabilitation with composite resins when using an indirect application and direct techniques, with the support of the Lucia Jig technique, the Willis technique, and diagnostic waxing for the vertical dimension correction. The wide clinical improvement was achieved with the recovery of the function, the esthetics, and the increase of vertical dimension of occlusion through the planned treatment. The proposed treatment maintained the natural teeth, without the intense wear by the application of the composite resins instead of ceramics, together with excellent conditions for the patient to control the posttreatment and extend the durability, with the correct follow-up of appointments. Young patients with extensive dental wear and the loss of vertical dimension should not be directly submitted to ceramic treatments, with preparations for full crowns. Oral rehabilitation using composite resins, either directly or indirectly, allows for the recovery of the function and esthetics, without the intense predictable dental wear, and reduced financial investment.

Innovative surfaces and alloys for dental implants: What about biointerface-safety concerns?

OBJECTIVES: The present review article aimed to discuss the recent technologies employed for the development of dental implants, mainly regarding innovative surface treatments and alternative alloys, emphasizing the bio-tribocorrosion processes. METHODS: An electronic search applying specific MeSH terms was carried out in PubMed and Google Scholar databases to collect data until August 2021, considering basic, pre-clinical, clinical and review studies. The relevant articles (n=111), focused on innovative surface treatments for dental implants and their potential undesirable biological effects, were selected and explored. RESULTS: Novel texturization methodologies for dental implants clearly provided superficial and structural atomic alterations in micro- and nanoscale, promoting different mechanical-chemical interactions when applied in the clinical set. Some particulate metals released from implant surfaces, their degradation products and/or contaminants exhibited local and systemic reactions after implant installation and osseointegration, contributing to unexpected treatment drawbacks and adverse effects. Therefore, there is an urgent need for development of pre-clinical and clinical platforms for screening dental implant devices, to predict the biointerface reactions as early as possible during the development phases. SIGNIFICANCE: Modern surface treatments and innovative alloys developed for dental implants are not completely understood regarding their integrity during long-term clinical function, especially when considering the bio-tribocorrosion process. From this review, it is possible to assume that degradation and contamination of dental surfaces might be associated within peri-implant inflammation and cumulative long-lasting systemic toxicity. The in-depth comprehension of the biointerface modifications on these novel surface treatments might preclude unnecessary expenses and postoperative complications involving osseointegration failures.

Influence of saliva interaction on surface properties manufactured for rapid osseointegration in dental implants.

Surface treatments are designed to promote modified implant surfaces with positive interactions with the surrounding living tissues. However, the inadvertent early contact of these surfaces with oral fluids during surgery may lead to undesired conditions affecting osseointegration. This study aimed to investigate the possible alterations in the physico-chemical properties of modified-surfaces caused by early saliva exposure. Titanium (Ti) surfaces were exposed to three different samples of human saliva and later analyzed for protein adhesion, physico-chemical surface alterations, and osteogenic cell-viability. The results indicated that surface roughness was the most significant factor influencing saliva protein adsorption; moreover, hydrophilic surfaces had critically lost their characteristics after contact with saliva. Decreased cell viability was observed in cultures after contact with saliva. Early contact with saliva might negatively influence modified surface properties and local cell viability. Careful surgical insertion of implants with hydrophilic surfaces is recommended, particularly in sites where saliva interaction is prone to occur.

Oral Tissue Interactions and Cellular Response to Zirconia Implant-Prosthetic Components: A Critical Review.

BACKGROUND: Dental components manufactured with zirconia (ZrO2) represent a significant percentage of the implant prosthetic market in dentistry. However, during the last few years, we have observed robust clinical and pre-clinical scientific investigations on zirconia both as a prosthetic and an implantable material. At the same time, we have witnessed consistent technical and manufacturing updates with regards to the applications of zirconia which appear to gradually clarify points which until recently were not well understood. METHODS: This critical review evaluated the "state of the art" in relation to applications of this biomaterial in dental components and its interactions with oral tissues. RESULTS: The physico-chemical and structural properties as well as the current surface treatment methodologies for ZrO2 were explored. A critical investigation of the cellular response to this biomaterial was completed and the clinical implications discussed. Finally, surface treatments of ZrO2 demonstrate that excellent osseointegration is possible and provide encouraging prospects for rapid bone adhesion. Furthermore, sophisticated surface treatment techniques and technologies are providing impressive oral soft tissue cell responses thus leading to superior biological seal. CONCLUSIONS: Dental devices manufactured from ZrO2 are structurally and chemically stable with biocompatibility levels allowing for safe and long-term function in the oral environment.

Metallic-nanoparticle release systems for biomedical implant surfaces: effectiveness and safety.

The current focus of bioengineering for implant devices involves the development of functionalized surfaces, bioactive coatings, and metallic nanoparticles (mNPs) with a controlled release, together with strategies for the application of drugs in situ, aiming at reducing infection rates, with an improvement of clinical outcomes. Controversially, negative aspects, such as cytotoxicity, mNP incorporation, bioaccumulation, acquired autoimmunity, and systemic toxicity have gained attention at the same status of importance, concerning the release of mNPs from these surface systems. The balance between the promising prospects of system releasing mNPs and the undesirable long-term adverse reactions require further investigation. The scarcity of knowledge and the methods of analysis of nanoscale-based systems to control the sequence of migration, interaction, and nanoparticle incorporation with human tissues raise hesitation about their efficacy and safety. Looking ahead, this innovative approach requires additional scientific investigation for permitting an evolution of implants without counterpoints, while updating implant surface technologies to a new level of development. This critical review has explored the promising properties of metals at the nano-scale to promote broad-spectrum bacterial control, allowing for a decrease in using systemic antibiotics. Attempts have also been made to discuss the existing limitations and the future challenges regarding these technologies, besides the negative findings that are explored in the literature.

Nanointeraction: The profound influence of nanostructured and nano-drug delivery biomedical implant surfaces on cell behavior.

Nanostructured surfaces feature promising biological properties on biomaterials attracting large interest at basic research, implant industry development, and bioengineering applications. Thou, nanoscale interactions at a molecular and cellular level are not yet completely understood and its biological and clinical implications need to be further elucidated. As follows, the aim of this comprehensive review was to evaluate nanostructured surfaces at biomedical implants focusing on surface development, nanostructuration, and nanoengineered drug delivery systems that can induce specific cell interactions in all relevant aspects of biological, reparative, anti-bacterial, anti-inflammatory and clinical processes. The methods and the physio-chemical properties involved in nanotopography performance, the main cellular characteristics involved at surface/cell interaction, and a summary of results and outlooks reported in studies applying nanostructured surfaces and nano-drug delivery systems is presented. The future prospects and commercial translation of this developing field, particularly concerning multifunctional nanostructured surfaces and its clinical implications are further discussed. At a cellular level, nanostructured biomedical implant surfaces can enhance osteogenesis by targeting osteoblasts, osteocytes, and mesenchymal cells, stimulate fibroblast/epithelial cells proliferation and adherence, inhibit bacterial cell proliferation and biofilm accumulation, and act as immune-modulating surfaces targeting macrophages and reducing pro-inflammatory cytokine expression. Moreover, several methodological options to create drug-delivery systems on metallic implant surfaces are available, however, the clinical translation is yet incomplete. The efficiency of which nanostructured/nano-delivery surfaces may target specific cell interactions and favor clinical outcomes needs to be further elucidated in pre-clinical and clinical studies, along with engineering solutions for commercial translation and approval of controlling agencies.

Extension of hydrophilicity stability by reactive plasma treatment and wet storage on TiO2 nanotube surfaces for biomedical implant applications.

Micro and nanoscale changes allow the optimization of physico-chemical properties of titanium implant surfaces. Recently UV and plasma treatments have allowed surface hydrophilicity to take increased prominence; however, this beneficial effect is short-lived. The aim of this study is to investigate methodologies post-anodizing treatment to generate and maintain high surface hydrophilicity along with high biocompatibility. Anodized surfaces were characterized regarding physical-chemical properties. Then, surface wettability with nanomorphology was evaluated at different times and with distinct post-treatments: as deposited, with a reactive plasma and UV-light post-treatment, stored in air or deionized (DI) water. Adhesion, alkaline phosphatase (ALP) activity and bone cell viability tests were executed after the incremental treatments. The anodizing process generated a surface with TiO2 nanotubes morphology and micro-roughness. Plasma-treated surfaces resulted in the most hydrophilic samples and this property was maintained for a longer period when those were stored in DI water (angle variation of 7° to 12° in 21 days). Furthermore, plasma post-treatment changed the titanium surface crystalline phase from amorphous to anatase. Anodized surfaces modified by reactive plasma and stored in DI water suggest better hydrophilicity stability, biocompatibility, ALP activity and achievement of crystalline phase alteration, indicating future potential use on biomedical implants.

Influence of titanium and zirconia modified surfaces for rapid healing on adhesion and biofilm formation of Staphylococcus epidermidis.

OBJECTIVE: Surface alterations have been employed to enhance the osseointegration process in biomedical implants. However, these modifications may influence bacterial adhesion in different ways. Therefore, this study developed five different surfaces and evaluated the Staphylococcus epidermidis growth in early (1 h) and late (24 h) contact. DESIGN: The Titanium (Ti) and Zirconia (Zr) surfaces were divided in five groups and characterized concerning your morphology, roughness, wettability and chemical surface composition. Then, were evaluated regarding bacterial adhesion and biofilm formation/thickness, viability and morphology. RESULTS: Different topographies were manufactured resulting in a variety of combinations of surface properties. High roughness showed significantly higher bacterial adhesion in 1 h, while high hydrophilicity revealed greater bacterial proliferation in 24 h. Morphological changes were not found visually, however the viability test showed some cell membrane damage in the Ti micro and nano groups. CONCLUSIONS: Finally, surface distinct properties influence the growth of S. epidermidis independent of the based-material. Furthermore, some surface properties require precautions for use in contaminated sites according to the increased adhesion of S. epidermidis presented when in contact.