In Situ Transformation of Chitosan Films into Microtubular Structures on the Surface of Nanoengineered Titanium Implants.

There is considerable interest in combining bioactive polymers such as chitosan with titanium bone implants to promote bone healing and address therapeutic needs. However, the fate of these biodegradable polymers especially on titanium implants is not fully explored. Here we report in situ formation of chitosan microtube (CMT) structures from chitosan films on the implant surface with titania nanotubes (TNTs) layer, based on phosphate buffer-induced transformation and precipitation process. We have comprehensively analyzed this phenomenon and the factors that influence CMT formation, including substrate topography, immersion solution and its pH, effect of coating thickness, and time of immersion. Significance of reported in situ formation of chitosan microtubes on the TNTs surface is possibly to tailor properties of implants with favorable micro and nano morphology using a self-ordering process after the implant's insertion.

Load, unload and repeat: Understanding the mechanical characteristics of zirconia in dentistry.

OBJECTIVES: Zirconia-based dental restorations and implants are gaining attention due to their bioactivity, corrosion resistance and mechanical stability. Further, surface modification of zirconia implants has been performed at the macro-, micro- and nanoscale to augment bioactivity. While zirconia's physical and chemical characteristics have been documented, its relation to mechanical performance still needs to be explored. This extensive review aims to address this knowledge gap. METHODS: This review critically compares and contrasts the findings from articles published in the domain of 'mechanical stability of zirconia\ in dentistry' based on a literature survey (Web of Science, Medline/PubMed and Scopus databases) and a review of the relevant publications in international peer-reviewed journals. Reviewing the published data, the mechanical properties of zirconia, such as fracture resistance, stress/tension, flexural strength, fatigue, and wear are detailed and discussed to understand the biomechanical compatibility of zirconia with the mechanical performance of modified zirconia in dentistry also explored. RESULTS: A comprehensive insight into dental zirconia's critical fundamental mechanical characteristics and performance is presented. Further, research challenges and future directions in this domain are recommended. SIGNIFICANCE: This review extends existing knowledge of zirconia's biomechanical performance and it they can be modulated to design the next generation of zirconia dental restorations and implants to withstand long-term constant loading.

Profiling to Probing: Atomic force microscopy to characterize nano-engineered implants.

Surface modification of implants in the nanoscale or implant nano-engineering has been recognized as a strategy for augmenting implant bioactivity and achieving long-term implant success. Characterizing and optimizing implant characteristics is crucial to achieving desirable effects post-implantation. Modified implant enables tailored, guided and accelerated tissue integration; however, our understanding is limited to multicellular (bulk) interactions. Finding the nanoscale forces experienced by a single cell on nano-engineered implants will aid in predicting implants' bioactivity and engineering the next generation of bioactive implants. Atomic force microscope (AFM) is a unique tool that enables surface characterization and understanding of the interactions between implant surface and biological tissues. The characterization of surface topography using AFM to gauge nano-engineered implants' characteristics (topographical, mechanical, chemical, electrical and magnetic) and bioactivity (adhesion of cells) is presented. A special focus of the review is to discuss the use of single-cell force spectroscopy (SCFS) employing AFM to investigate the minute forces involved with the adhesion of a single cell (resident tissue cell or bacterium) to the surface of nano-engineered implants. Finally, the research gaps and future perspectives relating to AFM-characterized current and emerging nano-engineered implants are discussed towards achieving desirable bioactivity performances. This review highlights the use of advanced AFM-based characterization of nano-engineered implant surfaces via profiling (investigating implant topography) or probing (using a single cell as a probe to study precise adhesive forces with the implant surface). STATEMENT OF SIGNIFICANCE: Nano-engineering is emerging as a surface modification platform for implants to augment their bioactivity and achieve favourable treatment outcomes. In this extensive review, we closely examine the use of Atomic Force Microscopy (AFM) to characterize the properties of nano-engineered implant surfaces (topography, mechanical, chemical, electrical and magnetic). Next, we discuss Single-Cell Force Spectroscopy (SCFS) via AFM towards precise force quantification encompassing a single cell's interaction with the implant surface. This interdisciplinary review will appeal to researchers from the broader scientific community interested in implants and cell adhesion to implants and provide an improved understanding of the surface characterization of nano-engineered implants.

Advancing Nitinol: From heat treatment to surface functionalization for nickel-titanium (NiTi) instruments in endodontics.

Nickel-titanium (NiTi) alloy has been extensively researched in endodontics, particularly in cleaning and shaping the root canal system. Research advances have primarily focused on the design, shape, and geometry of the NiTi files as well as metallurgy and mechanical properties. So far, extensive investigations have been made surrounding surface and thermomechanical treatments, however, limited work has been done in the realm of surface functionalization to augment its performance in endodontics. This review summarizes the unique characteristics, current use, and latest developments in thermomechanically treated NiTi endodontic files. It discusses recent improvements in nano-engineering and the possibility of customizing the NiTi file surface for added functionalization. Whilst clinical translation of this technology has yet to be fully realized, future research direction will lie in the use of nanotechnology.

Enhanced Corrosion Resistance and Local Therapy from Nano-Engineered Titanium Dental Implants.

Titanium is the ideal material for fabricating dental implants with favorable biocompatibility and biomechanics. However, the chemical corrosions arising from interaction with the surrounding tissues and fluids in oral cavity can challenge the integrity of Ti implants and leach Ti ions/nanoparticles, thereby causing cytotoxicity. Various nanoscale surface modifications have been performed to augment the chemical and electrochemical stability of Ti-based dental implants, and this review discusses and details these advances. For instance, depositing nanowires/nanoparticles via alkali-heat treatment and plasma spraying results in the fabrication of a nanostructured layer to reduce chemical corrosion. Further, refining the grain size to nanoscale could enhance Ti implants' mechanical and chemical stability by alleviating the internal strain and establishing a uniform TiO2 layer. More recently, electrochemical anodization (EA) has emerged as a promising method to fabricate controlled TiO2 nanostructures on Ti dental implants. These anodized implants enhance Ti implants' corrosion resistance and bioactivity. A particular focus of this review is to highlight critical advances in anodized Ti implants with nanotubes/nanopores for local drug delivery of potent therapeutics to augment osseo- and soft-tissue integration. This review aims to improve the understanding of novel nano-engineered Ti dental implant modifications, focusing on anodized nanostructures to fabricate the next generation of therapeutic and corrosion-resistant dental implants. The review explores the latest developments, clinical translation challenges, and future directions to assist in developing the next generation of dental implants that will survive long-term in the complex corrosive oral microenvironment.

Craniofacial therapy: advanced local therapies from nano-engineered titanium implants to treat craniofacial conditions.

Nano-engineering-based tissue regeneration and local therapeutic delivery strategies show significant potential to reduce the health and economic burden associated with craniofacial defects, including traumas and tumours. Critical to the success of such nano-engineered non-resorbable craniofacial implants include load-bearing functioning and survival in complex local trauma conditions. Further, race to invade between multiple cells and pathogens is an important criterion that dictates the fate of the implant. In this pioneering review, we compare the therapeutic efficacy of nano-engineered titanium-based craniofacial implants towards maximised local therapy addressing bone formation/resorption, soft-tissue integration, bacterial infection and cancers/tumours. We present the various strategies to engineer titanium-based craniofacial implants in the macro-, micro- and nano-scales, using topographical, chemical, electrochemical, biological and therapeutic modifications. A particular focus is electrochemically anodised titanium implants with controlled nanotopographies that enable tailored and enhanced bioactivity and local therapeutic release. Next, we review the clinical translation challenges associated with such implants. This review will inform the readers of the latest developments and challenges related to therapeutic nano-engineered craniofacial implants.

Microvesicle-eluting nano-engineered implants influence inflammatory response of keratinocytes.

Besides enhancing osseo- and soft tissue integration, modulating inflammation at the implant site is also crucial for dental implant success. Uncontrolled peri-implant inflammation can cause significant loss of surrounding tissue and implant failure. It was recently shown that microvesicles (MVs), a less-studied type of extracellular vesicles, play a crucial role in cell-to-cell communication and may modulate angiogenesis and inflammatory response. The effect of MVs on regulating inflammation at an implant site, however, remains unexplored. In the current study, MVs were isolated and characterised from human primary gingival fibroblasts (hGFs) and loaded within titania nanotubes (TNTs, fabricated via anodisation on 3D Ti wire implants) towards their local release. The modified implants were characterised using SEM and confocal imaging to confirm the loading and local release of MVs from TNTs. In vitro studies demonstrated the internalisation of hGFs-MVs by human gingival keratinocytes (OKF6/TERT2 cell line), which caused a significant reduction in the production of pro-inflammatory cytokines. The results support MVs-releasing TNTs as a promising implant surface modification strategy to reduce inflammation, paving the way for further advancements in therapeutic dental implants.

Fit and forget: The future of dental implant therapy via nanotechnology.

Unlike orthopedic implants, dental implants require the orchestration of both osseointegration at the bone-implant interface and soft-tissue integration at the transmucosal region in a complex oral micro-environment with ubiquitous pathogenic bacteria. This represents a very challenging environment for early acceptance and long-term survival of dental implants, especially in compromised patient conditions, including aged, smoking and diabetic patients. Enabling advanced local therapy from the surface of titanium-based dental implants via novel nano-engineering strategies is emerging. This includes anodized nano-engineered implants eluting growth factors, antibiotics, therapeutic nanoparticles and biopolymers to achieve maximum localized therapeutic action. An important criterion is balancing bioactivity enhancement and therapy (like bactericidal efficacy) without causing cytotoxicity. Critical research gaps still need to be addressed to enable the clinical translation of these therapeutic dental implants. This review informs the latest developments, challenges and future directions in this domain to enable the successful fabrication of clinically-translatable therapeutic dental implants that would allow for long-term success, even in compromised patient conditions.

Nano-Engineering Solutions for Dental Implant Applications.

This Special Issue of Nanomaterials explores the recent advances and trends with respect to nano-engineered strategies towards dental implant applications [...].

Novel Nano-Engineered Biomaterials for Bone Tissue Engineering.

This Special Issue of Nanomaterials explores the recent advances relating to nano-engineered strategies for biomaterials and implants in bone tissue engineering [...].

Research to Clinics: Clinical Translation Considerations for Anodized Nano-Engineered Titanium Implants.

Titania nanotubes (TNTs) fabricated on titanium orthopedic and dental implants have shown significant potential in "proof of concept" in vitro, ex vivo, and short-term in vivo studies. However, most studies do not focus on a clear direction for future research towards clinical translation, and there exists a knowledge gap in identifying key research challenges that must be addressed to progress to the clinical setting. This review focuses on such challenges with respect to anodized titanium implants modified with TNTs, including optimized fabrication on clinically utilized microrough surfaces, clinically relevant bioactivity assessments, and controlled/tailored local release of therapeutics. Further, long-term in vivo investigations in compromised animal models under loading conditions are needed. We also discuss and detail challenges and progress related to the mechanical stability of TNT-based implants, corrosion resistance/electrochemical stability, optimized cleaning/sterilization, packaging/aging, and nanotoxicity concerns. This extensive, clinical translation focused review of TNTs modified Ti implants aims to foster improved understanding of key research gaps and advances, informing future research in this domain.

Understanding the influence of electrolyte aging in electrochemical anodization of titanium.

Titania nanotubes or nanopores self-ordered on electrochemically anodized (EA) titanium have been widely applied towards photocatalysis, solar cells, purification and biomedical implants. As a result, significant research has been focused towards optimizing anodization to fabricate controlled, stable and reproducible nanostructures. Among these, the use of organic-based electrolyte, like ethylene glycol (with NH4F and water), to anodize Ti has been widely applied and researched. Interestingly, among the various influencing EA factors, electrolyte aging (repeated EA using non-target Ti, prior to EA of target Ti substrate) has been underexplored, with only few studies aiming to optimize electrolyte aging and its influence on the nanostructures fabricated. Moreover, many research laboratories utilize electrolyte aging in Ti anodization, but this practice is seldom reported. In this extensive and pioneering review, we discuss and detail electrolyte aging in Ti anodization to fabricate controlled nanostructures, and its influence on nanostructure characteristics including morphology, chemistry, stability and application-specific performance. This review will inform future research aimed at optimizing electrolyte aging and Ti anodization to fabricate controlled nanostructures catering to specific application needs.

Advancing dental implants: Bioactive and therapeutic modifications of zirconia.

Zirconium-based implants have gained popularity in the dental implant field owing to their corrosion resistance and biocompatibility, attributed to the formation of a native zirconia (ZrO2) film. However, enhanced bioactivity and local therapy from such implants are desirable to enable the earlier establishment and improved long-term maintenance of implant integration, especially in compromised patient conditions. As a result, surface modification of zirconium-based implants have been performed using various physical, chemical and biological techniques at the macro-, micro-, and nano-scales. In this extensive review, we discuss and detail the development of Zr implants covering the spectrum from past and present advancements to future perspectives, arriving at the next generation of highly bioactive and therapeutic nano-engineered Zr-based implants. The review provides in-depth knowledge of the bioactive/therapeutic value of surface modification of Zr implants in dental implant applications focusing on clinical translation.

Influence of Clinical Decontamination Techniques on the Surface Characteristics of SLA Titanium Implant.

The study aims: 1. To perform diode laser, titanium (Ti) brush, and Ti curette treatment on sandblasted and acid-etched (SLA) Ti surfaces, with/without H2O2 and CHX, 2. To investigate the influence of decontamination techniques on implant surface topography and hydrophilicity. Diode laser, Ti brush, and Ti curette treatments were performed on the Grade 4 Ti discs, with/without treatment with 3% H2O2 solution or 0.2% CHX. Surface characteristics were investigated via SEM, optical profilometry, and water contact angle meter. SEM findings revealed flat and scratched areas when treated with Ti curette and Ti brush. For diode laser, SEM showed melting in specific areas. Ra and Rt values were lower in all test groups than in the control group (p < 0.05). The adjunctive chemical treatment showed negligible effects in SEM images and surface roughness measurements compared to laser and mechanical treatment-only groups. H2O2 treatment resulted in enhanced hydrophilicity in either treatment modalities with a significant difference compared to the negative control group (p < 0.05). In all test groups, the hydrophilicity was enhanced compared to the negative control group (p < 0.05). Diode laser treatment had the least disruptive effect on the Ti surface characteristics. The use of other mechanical methods caused significant alterations in the surface roughness.

ON or OFF: Triggered therapies from anodized nano-engineered titanium implants.

Surface modification of Ti implants has been advocated as a means to augment osseointegration and enable antibacterial functions. Among the various modification strategies, the fabrication of TiO2 nanotubes (TNTs) on Ti implants via electrochemical anodization has shown promising outcomes. However, such systems do not enable activation, deactivation and tuning of the therapies after the implant placement, in response to local bone microenvironment conditions, to achieve a maximal therapeutic effect. Therapies administered from the implant surface in situ and managed by internal/external triggers can shift the paradigm in providing responsive therapy. In this review, we explore the various triggers that have been employed to achieve triggered therapies from the surface of modified Ti implants, with special focus on TNTs. We critically evaluate the current research advances in this domain (including biological, electrical, magnetic and electromagnetic triggers), cytotoxicity concerns and research challenges that must be addressed to achieve clinical translation of triggered therapies from modified Ti implants.

Understanding and optimizing the antibacterial functions of anodized nano-engineered titanium implants.

Nanoscale surface modification of titanium-based orthopaedic and dental implants is routinely applied to augment bioactivity, however, as is the case with other cells, bacterial adhesion is increased on nano-rough surfaces. Electrochemically anodized Ti implants with titania nanotubes (TNTs) have been proposed as an ideal implant surface with desirable bioactivity and local drug release functions to target various conditions. However, a comprehensive state of the art overview of why and how such TNTs-Ti implants acquire antibacterial functions, and an in-depth knowledge of how topography, chemistry and local elution of potent antibiotic agents influence such functions has not been reported. This review discusses and details the application of nano-engineered Ti implants modified with TNTs for maximum local antibacterial functions, deciphering the interdependence of various characteristics and the fine-tuning of different parameters to minimize cytotoxicity. An ideal implant surface should cater simultaneously to ossoeintegration (and soft-tissue integration for dental implants), immunomodulation and antibacterial functions. We also evaluate the effectiveness and challenges associated with such synergistic functions from modified TNTs-implants. Particular focus is placed on the metallic and semi-metallic modification of TNTs towards enabling bactericidal properties, which is often dose dependent. Additionally, there are concerns over the cytotoxicity of these therapies. In that light, research challenges in this domain and expectations from the next generation of customizable antibacterial TNTs implants towards clinical translation are critically evaluated. STATEMENT OF SIGNIFICANCE: One of the major causes of titanium orthopaedic/dental implant failure is bacterial colonization and infection, which results in complete implant failure and the need for revision surgery and re-implantation. Using advanced nanotechnology, controlled nanotopographies have been fabricated on Ti implants, for instance anodized nanotubes, which can accommodate and locally elute potent antibiotic agents. In this pioneering review, we shine light on the topographical, chemical and therapeutic aspects of antibacterial nanotubes towards achieving desirable tailored antibacterial efficacy without cytotoxicity concerns. This interdisciplinary review will appeal to researchers from the wider scientific community interested in biomaterials science, structure and function, and will provide an improved understanding of controlling bacterial infection around nano-engineered implants, aimed at bridging the gap between research and clinics.

Micro + Nano: Conserving the Gold Standard Microroughness to Nanoengineer Zirconium Dental Implants.

Zirconium has achieved popularity as a biomaterial for dental and orthopedic implants; however, its bioinertness can compromise implant-tissue integration, especially in compromised patient conditions. More recently, various nanoengineering strategies have been explored to enhance the bioactivity of Ti-based implants; however, nanoengineering of Zr-based implants has not been adequately explored. In this pioneering attempt, we report on the optimized fabrication of various nanostructures on microrough Zr surfaces and explore the influence of the underlying surface topography. In-depth optimization of electrochemical anodization (EA) is performed by tuning various parameters, including substrate topography, voltage/current and time, onto microrough (micromachined) and extremely rough Zr substrates, which represent clinically relevant implant surfaces. Variations of EA factors yielded various nanotopographies, including nanotubes, nanograss and nanotemplates, offering different topographical and chemical combinations. EA optimization and precise current-voltage recording was performed to arrive at clinically translatable and reproducible nanostructures on Zr surfaces. This study will pave the way toward the fabrication of the next generation of nanoengineered Zr-based orthopedic and dental implants.

Towards Clinical Translation: Optimized Fabrication of Controlled Nanostructures on Implant-Relevant Curved Zirconium Surfaces.

Anodization enables fabrication of controlled nanotopographies on Ti implants to offer tailorable bioactivity and local therapy. However, anodization of Zr implants to fabricate ZrO2 nanostructures remains underexplored and are limited to the modification of easy-to-manage flat Zr foils, which do not represent the shape of clinically used implants. In this pioneering study, we report extensive optimization of various nanostructures on implant-relevant micro-rough Zr curved surfaces, bringing this technology closer to clinical translation. Further, we explore the use of sonication to remove the top nanoporous layer to reveal the underlying nanotubes. Nano-engineered Zr surfaces can be applied towards enhancing the bioactivity and therapeutic potential of conventional Zr-based implants.

Double-edged sword: Therapeutic efficacy versus toxicity evaluations of doped titanium implants.

Titanium-based orthopaedic/dental implants modified with various metal-doping strategies can enhance local therapy and bioactivity. Intentional or unintentional (because of loading and wear) release of metal ions/nanoparticles (NPs) from metal-doped implants can be therapeutic or cause adverse local tissue reactions, compromising long-term survival. Strategies to incorporate metals into implants, such as superficial or deep loading inside nano-engineered surfaces, including nanotubes, and the physiochemical characteristics of the released species significantly influence both their therapeutic and cytotoxic potential. In this review, we compare and contrast this 'double-edged sword' to arrive at an improved understanding of metal-doped implants to enable controlled therapy while minimising cytotoxicity concerns.

Dental Implant Nano-Engineering: Advances, Limitations and Future Directions.

Titanium (Ti) and its alloys offer favorable biocompatibility, mechanical properties and corrosion resistance, which makes them an ideal material choice for dental implants. However, the long-term success of Ti-based dental implants may be challenged due to implant-related infections and inadequate osseointegration. With the development of nanotechnology, nanoscale modifications and the application of nanomaterials have become key areas of focus for research on dental implants. Surface modifications and the use of various coatings, as well as the development of the controlled release of antibiotics or proteins, have improved the osseointegration and soft-tissue integration of dental implants, as well as their antibacterial and immunomodulatory functions. This review introduces recent nano-engineering technologies and materials used in topographical modifications and surface coatings of Ti-based dental implants. These advances are discussed and detailed, including an evaluation of the evidence of their biocompatibility, toxicity, antimicrobial activities and in-vivo performances. The comparison between these attempts at nano-engineering reveals that there are still research gaps that must be addressed towards their clinical translation. For instance, customized three-dimensional printing technology and stimuli-responsive, multi-functional and time-programmable implant surfaces holds great promise to advance this field. Furthermore, long-term in vivo studies under physiological conditions are required to ensure the clinical application of nanomaterial-modified dental implants.