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Titanium and its alloys, especially Ti-6Al-4V, are widely studied in implantology for their favorable characteristics. However, challenges remain, such as the high modulus of elasticity and concerns about cytotoxicity. To resolve these issues, research focuses on β-type titanium alloys that incorporate elements such as Mo, Nb, Sn, and Ta to improve corrosion resistance and obtain a lower modulus of elasticity compatible with bone. This review comprehensively examines current β titanium alloys, evaluating their mechanical properties, in particular the modulus of elasticity, and corrosion resistance. To this end, a systematic literature search was carried out, where 81 articles were found to evaluate these outcomes. In addition, this review also covers the formation of the alloy, processing methods such as arc melting, and its physical, mechanical, electrochemical, tribological, and biological characteristics. Because β-Ti alloys have a modulus of elasticity closer to that of human bone compared to other metal alloys, they help reduce stress shielding. This is important because the alloy allows for a more even distribution of forces by having a modulus of elasticity more similar to that of bone. In addition, these alloys show good corrosion resistance due to the formation of a noble titanium oxide layer, facilitated by the incorporation of β stabilizers. These alloys also show significant improvements in mechanical strength and hardness. Finally, they also have lower cytotoxicity and bacterial adhesion, depending on the β stabilizer used. However, there are persistent challenges that require detailed research in critical areas, such as optimizing the composition of the alloy to achieve optimal properties in different clinical applications. In addition, it is crucial to study the long-term effects of implants on the human body and to advance the development of cutting-edge manufacturing techniques to guarantee the quality and biocompatibility of implants.

Titanium (Ti) is widely used in medical and dental implants. Calcium phosphate (CPs) coatings enhance Ti implants' osteoinductive properties, and additives further improve these coatings. Recently, a nano amorphous calcium phosphate (nACP) coating decorated with chitosan oligolactate (ChOL) and selenium (Se) showed immunomodulatory effects. This study investigates the surface morphology, composition, bioactivity, mechanical properties, and Se-release mechanism of the nACP@ChOL-Se hybrid coating on Ti substrates. Amorphous calcium phosphate (ACP) was synthesized, and the nACP@ChOL-Se hybrid coating was deposited on Ti substrates using in situ anaphoretic deposition. Physico-chemical characterization was used to analyze the surface of the coating (scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier Transform Infrared Spectroscopy). The distribution of Se within the coating was examined with energy-dispersive X-ray spectroscopy (EDS). Bioactivity was evaluated in simulated body fluid (SBF), and adhesion was tested using a scratch test method. In vitro testing determined the release mechanism of Se. SEM images illustrated the surface morphology, while AFM provided a detailed analysis of surface roughness. XRD analysis revealed structural and phase composition, and EDS confirmed Se distribution within the coating. The coating exhibited bioactivity in SBF and showed good adhesion according to the scratch test. In vitro testing uncovered the release mechanism of Se from the coating. This study successfully characterized the surface morphology, composition, bioactivity, and Se-release mechanism of the nACP@ChOL-Se hybrid coating on Ti substrates, offering insights for developing immunomodulatory coatings for medical and dental applications., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

To study in vivo the bioactivity of biodegradable magnesium implants and other possible biomaterials, we are proposing a previously unexplored application of PET-CT imaging, using available tracers to follow soft tissue and bone remodelling and immune response in the presence of orthopaedic implants. Female Wistar rats received either implants (Ti6Al7Nb titanium or WE43 magnesium) or corresponding transcortical sham defects into the diaphyseal area of the femurs. Inflammatory response was followed with [ 18 F]FDG and osteogenesis with [ 18 F]NaF, over the period of 1.5 months after surgery. An additional pilot study with [ 68 Ga]NODAGA-RGD tracer specific to α v β 3 integrin expression was performed to follow the angiogenesis for one month. [ 18 F]FDG tracer uptake peaked on day 3 before declining in all groups, with Mg and Ti groups exhibiting overall higher uptake compared to sham. This suggests increased cellular activity and tissue response in the presence of Mg during the initial weeks, with Ti showing a subsequent increase in tracer uptake on day 45, indicating a foreign body reaction. [ 18 F]NaF uptake demonstrated the superior osteogenic potential of Mg compared to Ti, with peak uptake on day 7 for all groups. [ 68 Ga]NODAGA-RGD pilot study revealed differences in tracer uptake trends between groups, particularly the prolonged expression of α v β 3 integrin in the presence of implants. Based on the observed differences in the uptake trends of radiotracers depending on implant material, we suggest that PET-CT is a suitable modality for long-term in vivo assessment of orthopaedic biomaterial biocompatibility and underlying tissue reactions. STATEMENT OF SIGNIFICANCE: The study explores the novel use of positron emission tomography for the assessment of the influence that biomaterials have on the surrounding tissues. Previous related studies have mostly focused on material-related effects such as implant-associated infections or to follow the osseointegration in prosthetics, but the use of PET to evaluate the materials has not been reported before. The approach tests the feasibility of using repeated PET-CT imaging to follow the tissue response over time, potentially improving the methodology for adopting new biomaterials for clinical use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: The aim of this study was to determine clinically and genetically the allergic effects of titanium and poly-ether-ether-ketone (PEEK) implants following loading in rabbit tibias., Materials and Methods: This study included 18 white New Zealand male rabbits (n = 18) divided evenly into three groups: control, titanium (Ti), and PEEK (P). Clinically, the allergenic effect of titanium and PEEK was investigated by detecting the effect on lymph nodes. Furthermore, RT-PCR and ELISA were used to detect the expression of certain genes IL-6, TNF-α, OPG, RANKL, and RUNX-2 through both types of implants., Results: Our findings demonstrated that titanium implants induced enlarged lymph nodes, which PEEK did not. Overall, RT-PCR and ELISA techniques revealed that Ti implants had higher expression of the inflammatory genes IL-6 and TNF-α. Ti had the highest expression in OPG findings, while PEEK had the lowest. RANKL expression was highest in the control group and lowest in the PEEK group. RUNX-2 is the highest for the control group and the lowest for the titanium group., Conclusion: Although titanium implants elicited greater allergy responses than PEEK implants, titanium has the highest expression of bone formation genes and the lowest expression of bone resorption genes, making it preferable to PEEK., (© 2024 Wiley Periodicals LLC.)

Objective: A high sodium (HS) diet is believed to affect bone metabolism processes. Clarifying its impact on osseointegration of titanium (Ti) implants holds significant implications for postoperative dietary management of implanted patients., Methods: This investigation probed the impact of sodium ions (Na + ) on neovascularization and osteogenesis around Ti implants in vivo , utilizing micro-computed tomography, hematoxylin and eosin staining, and immunohistochemical analyses. Concurrently, in vitro experiments assessed the effects of varied Na + concentrations and exposure durations on human umbilical vein endothelial cells (HUVECs) and MC3T3-E1 cells., Results: In vivo , increased dietary sodium (0.8%-6.0%) led to a substantial decline in CD34 positive HUVECs and new bone formation around Ti implants, alongside an increase in inflammatory cells. In vitro , an increase in Na + concentration (140-150 mmol/L) adversely affected the proliferation, angiogenesis, and migration of HUVECs, especially with prolonged exposure. While MC3T3-E1 cells initially exhibited less susceptibility to high Na + concentrations compared to HUVECs during short-term exposure, prolonged exposure to a HS environment progressively diminished their proliferation, differentiation, and osteogenic capabilities., Conclusion: These findings suggest that HS diet had a negative effect on the early osseointegration of Ti implants by interfering with the process of postoperative vascularized bone regeneration., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: The revolution of orthopedic implant manufacturing is being driven by 3D printing of titanium implants for large bony defects such as those caused by diabetic Charcot arthropathy. Unlike traditional subtractive manufacturing of orthopedic implants, 3D printing fuses titanium powder layer-by-layer, creating a unique surface roughness that could potentially enhance osseointegration. However, the metabolic impairments caused by diabetes, including negative alterations of bone metabolism, can lead to nonunion and decreased osseointegration with traditionally manufactured orthopedic implants. This study aimed to characterize the response of both healthy and diabetic primary human osteoblasts cultured on a medical-grade 3D-printed titanium surface under high and low glucose conditions., Methods: Bone samples were obtained from six patients, three with Type 2 Diabetes Mellitus and three without. Primary osteoblasts were isolated and cultured on 3D-printed titanium discs in high (4.5 g/L D-glucose) and low glucose (1 g/L D-Glucose) media. Cellular morphology, matrix deposition, and mineralization were assessed using scanning electron microscopy and alizarin red staining. Alkaline phosphatase activity and L-lactate concentration was measured in vitro to assess functional osteoblastic activity and cellular metabolism. Osteogenic gene expression of BGLAP , COL1A1 , and BMP7 was analyzed using reverse-transcription quantitative polymerase chain reaction., Results: Diabetic osteoblasts were nonresponsive to variations in glucose levels compared to their healthy counterparts. Alkaline phosphatase activity, L-lactate production, mineral deposition, and osteogenic gene expression remained unchanged in diabetic osteoblasts under both glucose conditions. In contrast, healthy osteoblasts exhibited enhanced functional responsiveness in a high glucose environment and showed a significant increase in osteogenic gene expression of BGLAP , COL1A1 , and BMP7 (p<.05)., Conclusion: Our findings suggest that diabetic osteoblasts exhibit impaired responsiveness to variations in glucose concentrations, emphasizing potential osteoblast dysfunction in diabetes. This could have implications for post-surgery glucose management strategies in patients with diabetes. Despite the potential benefits of 3D printing for orthopedic implants, particularly for diabetic Charcot collapse, our results call for further research to optimize these interventions for improved patient outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Allen, Aitchison, Abar, Burbano, Montgomery, Droz, Danilkowicz and Adams.)

Orthopedic and dental implant failure continues to be a significant concern due to localized bacterial infections. Previous studies have attempted to improve implant surfaces by modifying their texture and roughness or coating them with antibiotics to enhance antibacterial properties for implant longevity. However, these approaches have demonstrated limited effectiveness. In this study, we attempted to engineer the titanium (Ti) alloy surface biomimetically at the nanometer scale, inspired by the cicada wing nanostructure using alkaline hydrothermal treatment (AHT) to simultaneously confer antibacterial properties and support the adhesion and proliferation of mammalian cells. The two modified Ti surfaces were developed using a 4 h and 8 h AHT process in 1 N NaOH at 230 °C, followed by a 2-hour post-calcination at 600 °C. We found that the control plates showed a relatively smooth surface, while the treatment groups (4 h & 8 h AHT) displayed nanoflower structures containing randomly distributed nano-spikes. The results demonstrated a statistically significant decrease in the contact angle of the treatment groups, which increased wettability characteristics. The 8 h AHT group exhibited the highest wettability and significant increase in roughness 0.72 ± 0.08 µm (P < 0.05), leading to more osteoblast cell attachment, reduced cytotoxicity effects, and enhanced relative survivability. The alkaline phosphatase activity measured in all different groups indicated that the 8 h AHT group exhibited the highest activity, suggesting that the surface roughness and wettability of the treatment groups may have facilitated cell adhesion and attachment and subsequently increased secretion of extracellular matrix. Overall, the findings indicate that biomimetic nanotextured surfaces created by the AHT process have the potential to be translated as implant coatings to enhance bone regeneration and implant integration., (© 2024. The Author(s).)

Introduction: The aim of this study was to measure the wear progress of three high performance polymers (HPP) materials as well as that of zirconia after artificial aging (simulated 2.5- and 5-year of clinical service with thermo-mechanical loading) and compare it with the well-documented wear of lithium disilicate., Methods: Forty implants were used to restore a maxillary first premolar, where the abutment and the crown were manufactured as hybrid-abutment-crown and connected to the implant using a titanium insert. The implants were randomly divided, according to the restorative materials used, into five groups: 3Y-TZP zirconia (Z), lithium disilicate (L), ceramic-reinforced polyetheretherketon (P), nano-hybrid composite resin (C) and polymer-infiltrated ceramic-network (E). All hybrid-abutment-crowns were produced using CAD/CAM technology. A design of a maxillary first premolar was created with an angle of 120° between the buccal and palatal cusps, which were designed as planes. The restorations were adhesively luted onto the titanium inserts, according to the manufacturers' recommendations for each material individually, by means of dual-curing luting resin with the exception of group P, where the blocks were pre-fitted (heat-pressed) with an integrated titanium insert. The suprastructures were assembled onto the implants through titanium screws. The screw channels were sealed with Teflon tape and composite resin filling material that was polished to high-gloss. All specimens underwent 1 200 000 thermo-dynamic loading cycles with 49 N in a dual-axis chewing simulator. Elastomeric impressions were made for all specimens after 600 000 and after 1 200 000 cycles. The corresponding impressions were imaged using a laser scanning microscope and then 3D-analyzed using the software (Geomagic Wrap) to measure the volume loss of the wear area for all specimens. Statistical analysis was performed using Wilcoxon-Test regarding the two different time measurements for each material. For the analysis of the material variable, Kruskal-Wallis test was conducted followed by Mann-Whitney test., Results: Group Z showed statistically the lowest volume loss compared to the other test materials, both after 600 000 and 1 200 000 cycles of artificial aging, with a median value of 0.002 mm 3 volume loss after 1 200 000 cycles. In contrast, group E showed the highest volume loss with median values of 0.18 and 0.3 mm 3 after 600 000 and 1 200 000 cycles, respectively. Artificial aging had significantly negative effect on the volume loss for all test materials. In addition, the choice of material had statistical influence on the outcome., Conclusion: Monolithic zirconia ceramic demonstrated lower wear than that reported for enamel after simulated 5-year of clinical service, whereas all other test materials showed higher volume loss after artificial aging., (© 2023 The Authors. Clinical Implant Dentistry and Related Research published by Wiley Periodicals LLC.)

The design of implantable biomaterials involves precise tuning of surface features because the early cellular fate on such engineered surfaces is highly influenced by many physicochemical factors [roughness, hydrophilicity, reactive oxygen species (ROS) responsiveness, etc.]. Herein, to enhance soft tissue integration for successful implantation, Ti substrates decorated with uniform layers of nanoceria (Ce), called Ti@Ce, were optimally developed by a simple and cost-effective in situ immersion coating technique. The characterization of Ti@Ce shows a uniform Ce distribution with enhanced roughness (∼3-fold increase) and hydrophilicity (∼4-fold increase) and adopted ROS-scavenging capacity by nanoceria coating. When human gingival fibroblasts were seeded on Ti@Ce under oxidative stress conditions, Ti@Ce supported cellular adhesion, spreading, and survivability by its cellular ROS-scavenging capacity. Mechanistically, the unique nanocoating resulted in higher expression of amphiphysin (a nanotopology sensor), paxillin (a focal adhesion protein), and cell adhesive proteins (collagen-1 and fibronectin). Ti@Ce also led to global chromatin condensation by decreasing histone 3 acetylation as an early differentiation feature. Transcriptome analysis by RNA sequencing confirmed the chromatin remodeling, antiapoptosis, antioxidant, cell adhesion, and TGF-β signaling-related gene signatures in Ti@Ce. As key fibroblast transcription (co)factors, Ti@Ce promotes serum response factor and MRTF-α nucleus localization. Considering all of this, it is proposed that the surface engineering approach using Ce could improve the biological properties of Ti implants, supporting their functioning at soft tissue interfaces and utilization as a bioactive implant for clinical conditions such as peri-implantitis.

While titanium dental implants have already been clinically established, ongoing research is continuously being conducted to advance the fields of osseointegration and bacterial resistance, seeking further improvements in these areas. In this study, we introduce an innovative method for treating titanium surfaces within tightly sealed packaging. Specifically, titanium discs, enclosed in surgical-grade packaging, underwent treatment using cold atmospheric plasma (CAP). The surfaces were thoroughly characterized in terms of wettability, crystalline structure, and chemical composition. Hemocompatibility analyses were conducted using blood diluted in sodium citrate (1:9) exposed to titanium discs for 30 min inside a CO 2 incubator at 37 °C. Subsequently, various blood parameters were evaluated, including prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet adhesion. Microbiological analyses were also performed using Pseudomonas aeruginosa (ATCC 27853) for 4 h at 37 °C. The treatment with CAP Jet resulted in a reduction in contact angle without causing any changes in the crystalline structure. No statistically significant differences were observed in the blood parameters. The plasma-treated samples exhibited lower PT and APTT values compared to those of the control group. The surfaces treated with CAP Jet showed increased platelet activation, platelet density, and thrombus formation when compared with the untreated samples. Moreover, the treated surfaces demonstrated lower bacterial colony formation compared with other surfaces.

Commercial purity titanium (cp-Ti) is considered for replacing Ti64 as an implant material in various applications, due to the potential toxicity associated with the release of Al and V ions. However, the mechanical properties of cp-Ti, particularly fatigue resistance, are inadequate for this purpose. In this study, cp-Ti grade 4 rods were processed using a combination of equal channel angular pressing and rotary swaging (ECAP/RS). Tensile and fatigue tests were conducted, along with detailed microscopy and evaluation of corrosion resistance and biocompatibility. An average yield strength of 1383 MPa was obtained while maintaining moderate ductility of 10 %. This represents the highest strength ever recorded for cp-Ti, even exceeding that of Ti64. Additionally, fatigue endurance limit increased by 43 % up to 600 MPa, almost obtaining that of Ti64. Strengthening mechanisms were attributed to the ultrafine-grained (UFG) microstructure generated by ECAP/RS, along with strong crystallographic texture and formation of sub-grain structure. Furthermore, the corrosion resistance and biocompatibility of cp-Ti were largely unaffected, potentially easing regulatory transition in future medical devices. Thus, these results demonstrate high potential of combined ECAP/RS processing to manufacture UFG cp-Ti grade 4 materials that prospectively allow for the substitution of questionable alloys and downsizing of medical implants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Over the past decade, titanium implants have gained popularity as the number of performed implantation operations has significantly increased. There are a number of methods for modifying the surface of biomaterials, which are aimed at extending the life of titanium implants. The developments in this field in recent years have required a comprehensive discussion of all the properties of electrophoretically deposited coatings on titanium and its alloys, taking into account their bioactivity. The development that took place in this field in recent years required a comprehensive discussion of all the properties of coatings electrophoretically deposited on titanium and its alloys, with particular emphasis on their bioactivity. Herein, we attempt to assess the influence of the electrophoretic deposition (EPD) process parameters on these coatings' biological and mechanical properties. Particular attention has been addressed to the in-vitro and in-vivo studies conducted hitherto. We have seen an increased interest in using titanium alloys without the addition of toxic compounds and gaps in the EPD field such as the uncommon endeavors to develop a "Design of experiments" approach as well as the lack of assessment of the surface free energy and detailed topography of electrophoretically deposited coatings. The exact correlation of coating properties with EPD process parameters still seems explicitly not understood, necessitating more future investigations. Ipso facto, the exact mechanism of particle agglomeration and Hamaker's law need to be fathomable., (© 2023 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals LLC.)

Skull reconstruction using cranial implants is often required for repairing skull defects caused due to trauma, diseases, or malignancy to protect intracranial structures. For relieving Intracranial Pressure (ICP) surgeons restore cranial defects either using natural bones or fabricated custom cranial implants. With the increase in Traumatic Brain Injuries (TBI) and challenges faced by TBI patients to regain normalcy, it is imperative to analyse the mechanical behaviour of skull-implant assemblies under some Head Injury Criteria (HIC). Medical grade materials including Titanium Alloys (Ti-6Al-4V) and Polyether-ether-ketone (PEEK) are used by fabricating Patient-Specific Implants (PSI) manufactured using 3D imaging, modelling and printing techniques. 3D technologies are preferred over conventional manufacturing methods, as they enable fabrication of custom shapes, sizes and properties for these PSI. For an effective attachment of PSI with a defective skull, a stable joint and plate arrangement as fixture plates is necessary at their interface. These fixtures can have variable numbers, design shapes, materials and location arrangements. This paper presents the Finite Element Method/Analysis (FEM/FEA) study of PSI attached to a defected skull for reconstruction, with linear shaped fixture configuration, when subjected to an external dynamic loading at 5 m/s, strain rate of 10s -1 to 243s -1 and ICP of 15mm Hg from three sides of the skull faces. Three different materials as Neoprene (soft), Concrete (medium rigid) and E-Glass (highly rigid) have been used, in the form of a rectangular thin cuboidal wall structure, at an angle of 45° with the skull face. Four linear shaped fixture plates which were simplest to design, were used to attach the PSI-skull assembly, to ensure that weight of the PSI-fixation assembly on the patient remains minimal, overall assembly has symmetrical fixations and efforts required by a surgeon for fitment of these plates remain minimal. Placement of these fixture plates has been optimized to encompass the complete PSI-skull interface section, due to which the stresses within all the assembly components (PSI, fixture plate and skull) reduced by nearly 2.5 times than the initial design and remained within yielding limits, thereby, averting any failure under heavy external dynamic loading., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prashant jindal reports financial support and administrative support were provided by Science and Engineering Research Board. Jogendra bharti reports financial support was provided by All India Council for Technical Education., (Copyright © 2023. Published by Elsevier Ltd.)

The inflammatory-associated corrosion of metallic dental and orthopedic implants causes significant complications, which may result in the implant's failure. The corrosion resistance can be improved with coatings and surface treatments, but at the same time, it might affect the ability of metallic implants to undergo proper osteointegration. In this work, alginate hydrogels with and without octacalcium phosphate (OCP) were made on 3D-printed (patterned) titanium alloys (Ti Group 2 and Ti-Al-V Group 23) to enhance their anticorrosion properties in simulated normal, inflammatory, and severe inflammatory conditions in vitro. Alginate (Alg) and OCP-laden alginate (Alg/OCP) hydrogels were manufactured on the surface of 3D-printed Ti substrates and were characterized with wettability analysis, XRD, and FTIR. The electrochemical characterization of the samples was carried out with open circuit potential, potentiodynamic polarization, and electrochemical impedance spectroscopy (EIS). It was observed that the hydrophilicity of Alg/OCP coatings was higher than that of pure Alg and that OCP phase crystallinity was increased when samples were subjected to simulated biological media. The corrosion resistance of uncoated and coated samples was lower in inflammatory and severe inflammatory environments vs. normal media, but the hydrogel coatings on 3D-printed Ti layers moved the corrosion potential towards more nobler values, reducing the corrosion current density in all simulated solutions. These measurements revealed that OCP particles in the Alg hydrogel matrix noticeably increased the electrical charge transfer resistance at the substrate and coating interface more than with Alg hydrogel alone.

Background: This study aims to evaluate the effects of the artifact removal algorithm on linear measurements of the buccal cortical plate by altering the voltage., Methods: Ten titanium fixtures were inserted at the site of central, lateral, canine, premolars and molars of dry human mandibles. Vertical height of buccal plate was measured using a digital caliper as a gold standard. Mandibles were scanned with 54 and 58 kVp. Other parameters were constant. Images were reconstructed with none, low, medium and high artifact removal modes. Two Oromaxillofacial radiologists evaluated and measured the buccal plate height using Romexis software. Statistical package for the social sciences (SPSS) version 24 was used for data analysis., Results: In medium and high modes, the difference between 54 and 58 kVp was significant (p < 0.001). No significance was noted by using low ARM (artifact removal mode) at the 54 kVp and 58 kVp., Conclusion: Using artifact removal in low voltage decreases the accuracy of linear measurement and buccal crest visibility. By using high voltage, artifact removal would have no significant effect on accuracy of linear measurements., (© 2023. The Author(s).)

Titanium anodization has been shown to produce crystalline oxides exhibiting photocatalytic reactions that form reactive oxygen species (ROS) when exposed to UV light. The ROS subsequently attack bacteria cells, and thus reduce bacteria attachment on titanium implant surfaces. Polyaniline (PANI) is a conductive polymer that has shown antibacterial properties when electropolymerized onto titanium. Our research group hypothesized the addition of PANI to crystalline titanium oxide surfaces would increase the available free electrons and thus increase photocatalytic activity (PCA). This research led to the development of a novel single-step anodization approach for PANI doping crystalline titanium oxide layers. The objective of the present study was to determine the proper aniline electrolyte concentration needed to maximize the PCA and reduce bacterial attachment on the formed oxides. Aniline concentrations up to 1 M were added into a 1 M sulfuric acid electrolyte. The formed oxides exhibited increased PANI surface coverage but decreased anatase and rutile crystalline titanium oxide phase formation with increasing aniline electrolyte concentrations. Despite exhibiting the lowest levels of anatase and rutile formation, the 0.75 M and 1 M aniline oxides with the greatest PANI surface coverage also exhibited the highest PCA levels. 1 M aniline oxides showed significantly higher PCA under UVA irradiation compared to oxides formed from aniline concentrations up to 0.5 M (p < 0.001). 0.75 M aniline oxides exhibited significant reductions in Staphylococcus aureus attachment with or without UVA irradiation compared to control oxides without PANI. MTT and live/dead assays confirmed cytocompatibility and nearly 100% cell viability for the PANI doped oxides., (© 2022 Wiley Periodicals LLC.)

Plasma electrolytic oxidation (PEO) is a low-cost, structurally reliable, and environmentally friendly surface modification method for orthopedic and dental implants. This technique is successful for the formation of porous, corrosion-resistant, and bioactive coatings, besides introducing antimicrobial compounds easily. Given the increase in implant-related infections, antimicrobial PEO-treated surfaces have been widely proposed to surmount this public health concern. This review comprehensively discusses antimicrobial implant surfaces currently produced by PEO in terms of their in vitro and in vivo microbiological and biological properties. We present a critical [part I] and evidence-based [part II] review about the plethora of antimicrobial PEO-treated surfaces. The mechanism of microbial accumulation on implanted devices and the principles of PEO technology to ensure antimicrobial functionalization by one- or multi-step processes are outlined. Our systematic literature search showed that particular focus has been placed on the metallic and semi-metallic elements incorporated into PEO surfaces to facilitate antimicrobial properties, which are often dose-dependent, without leading to cytotoxicity in vitro. Meanwhile, there are concerns over the biocompatibility of PEO and its long-term antimicrobial effects in animal models. We clearly highlight the importance of using clinically relevant infection models and in vivo long-term assessments to guarantee the rational design of antimicrobial PEO-treated surfaces to identify the 'finish line' in the race for antimicrobial implant surfaces., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Bone defects are seriously threatening the health of orthopedics patients and it is difficult for implants to accelerate bone regeneration without using bone growth factors. Herein, a fast photothermal ion therapeutic strategy is developed based on the bandgap engineering of nanostructured TiO 2 through (Si/P)-dual elemental doping by micro-arc oxidation treatment of titanium implants. The (Si/P)-dual doping can tune the surface bandgap structure of TiO 2 by decreasing bandgap and broadening valence band simultaneously, which is confirmed by density functional theory calculations. It not only endows the implants with a mildly photothermal effect under near-infrared (NIR) light irradiation, but also creates an (Si/P) ion-rich microenvironment around the implants. This photothermal ion microenvironment can tune the behaviors of osteoblasts by promoting p38/Smad and ERK signaling pathways of osteoblasts, thus significantly upregulating the expression of osteogenesis genes by the synergistic action of mild photothermal stimulation and increased release of Si/P ions. The in vivo results are also in good agreement with in vitro tests, i.e., under NIR light irradiation, the photothermally responsive TiO 2 enhances the bone formation and osteointegration with implants. Therefore, this kind of photothermal ion strategy is a promising remote and noninvasive therapeutic mode for promoting bone regeneration of Ti implants., (© 2022 Wiley-VCH GmbH.)

The success of dental implants lies in their strong and lasting integration into the patient's receiving bone. The first biological interactions at the implant surface determine the subsequent evolution of the integration process. In this study we set our objective to analyze the mechanistic interaction of the early regenerative matrix at implant surfaces modified with calcium ions (Ca) as compared to standard implant surfaces (NoCa). We put the surfaces in a Quartz Crystal Microbalance with Dissipation (QCM-D) to monitor the frequency shift ( f ) and the viscoelastic properties of the adsorbed biofilms and used Scanning Electron Microscopy (SEM) to visualize the resulting interfaces. Upon the addition of human blood plasma, Ca surfaces formed an adsorbed three-dimensional film attached to the surface (∆ f = -40 Hz), while with NoCa, the biofilm formed but was not attached to the surface (∆ f = 0 Hz). After 20 min in blood, two representative commercial implants with Ca and NoCa surfaces showed also distinct interfaces: Ca implants formed a visible clot attached to the implant which was composed mainly of platelets (Surface Coverage: 40 ± 20%) and some red blood cells (SC: 9 ± 3%) entrapped within a fibrin network (SC: 93 ± 5%). The NoCa implants were largely populated by red blood cells (SC: 67 ± 12%) with scarce fibrin remnants (SC: 3 ± 2%), and the implants showed no clot on their surfaces macroscopically. The pre-clinical and clinical results discussed in this work encourage the modification of titanium implant surfaces with calcium ions to improve the bone regenerative process. Taken together, these results add more information about the roles of Ca ions in bridging the formation of the provisional matrix at implant surfaces and their effects on implant osseointegration.

Delivering and retaining cells in areas of interest is an ongoing challenge in tissue engineering. Here we introduce a novel approach to fabricate osteoblast-loaded titanium suitable for cell delivery for bone integration, regeneration, and engineering. We hypothesized that titanium age influences the efficiency of protein adsorption and cell loading onto titanium surfaces. Fresh (newly machined) and 1-month-old (aged) commercial grade 4 titanium disks were prepared. Fresh titanium surfaces were hydrophilic, whereas aged surfaces were hydrophobic. Twice the amount of type 1 collagen and fibronectin adsorbed to fresh titanium surfaces than aged titanium surfaces after a short incubation period of three hours, and 2.5-times more fibronectin than collagen adsorbed regardless of titanium age. Rat bone marrow-derived osteoblasts were incubated on protein-adsorbed titanium surfaces for three hours, and osteoblast loading was most efficient on fresh titanium adsorbed with fibronectin. The number of osteoblasts loaded using this synergy between fresh titanium and fibronectin was nine times greater than that on aged titanium with no protein adsorption. The loaded cells were confirmed to be firmly attached and functional. The number of loaded cells was strongly correlated with the amount of protein adsorbed regardless of the protein type, with fibronectin simply more efficiently adsorbed on titanium surfaces than collagen. The role of surface hydrophilicity of fresh titanium surfaces in increasing protein adsorption or cell loading was unclear. The hydrophilicity of protein-adsorbed titanium increased with the amount of protein but was not the primary determinant of cell loading. In conclusion, the osteoblast loading efficiency was dependent on the age of the titanium and the amount of protein adsorption. In addition, the efficiency of protein adsorption was specific to the protein, with fibronectin being much more efficient than collagen. This is a novel strategy to effectively deliver osteoblasts ex vivo and in vivo using titanium as a vehicle.

Tailoring surface properties by layer-by-layer (LBL) deposition directed on the construction of complex multilayer coatings with nanoscale precision enables the development of novel structures and devices with desired functional properties (i.e., osseointegration, bactericidal activity, biocorrosion protection). Herein, electrostatic self-assembly was applied to fabricate biopolymer-based coatings involving chitosan (CSM) and alginate (AL) enriched with caffeic acid (CA) on Ti-6Al-7Nb alloyed surfaces. The method of CA grafting onto the chitosan backbone (CA-g-CSM) as well as all used reagents for implant functionalization were chosen as green and sustainable approach. The final procedure of surface modification of the Ti-6Al-7Nb alloy consists of three steps: (i) chemical treatment in Piranha solution, (ii) plasma chemical-activation of the Ti alloy surface in a RF CVD (Radio Frequency Chemical Vapour Deposition) reactor using Ar, O 2 and NH 3 gaseous precursors, and (iii) a multi-step deposition of bio-functional coatings via dip-coating method. Corrosion tests have revealed that the resulting chitosan-based coatings, also these involving CA, block the specimen surface and hinder corrosion of titanium alloy. Furthermore, the antioxidant layers are characterized by beneficial level of roughness (R a up ca. 350 nm) and moderate hydrophilicity (59°) with the dispersion part of conducive surface energy ca. 30 mJ/m 2 . Noteworthy, all coatings are biocompatible as the intact morphology of cultured eukaryotic cells ensured proper growth and proliferation, while exhibit bacteriostatic character, particularly in contact with Gram-(-) bacteria (E. coli). The study indicates that the applied simple sustainable strategy has contributed significantly to obtaining homogeneous, stable, and biocompatible while antibacterial biopolymer-based coatings., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Mechanical properties of porous metal coatings in load-bearing implants play a critical role in determining the in vivo lifetime. However, there is a knowledge gap in measuring the shear strength of porous metal coatings at the porous-dense interface. This study evaluated pore morphology dependence and strut-size on compression, shear deformation, and in vitro response of additively manufactured porous Ti6Al4V structures. Selective laser melting (SLM)-based additive manufacturing (AM) technique was used to process two types of structures with honeycomb cell design-one with constant cell-size of ∼470 μm with mean strut-size varying from 92 to 134 μm, and denoted as strut-size variation (SSV); and the other with a constant strut-size of ∼135 μm with mean cell-size varying from 580 to 740 μm, denoted as cell-size variation (CSV). It was observed that under compressive loading, changes in elastic modulus were more sensitive to variations in strut-size over cell-size. Under shear loading at the porous-dense interface, strength enhancement and material hardening were observed in both SSV and CSV samples due to pore-collapsing. Our results show that for hexagonal cell designs, shear behavior is more sensitive to variations in cell-size over strut-size, although elastic modulus is more sensitive to changes in strut-size for porous metallic structures. From in vitro hFOB analysis, it was observed that pore size of 670 μm demonstrated the highest osteoblast cell viability among porous structures with evidence of pore-bridging by cells. P. aeruginosa bacterial culture showed that bacterial cell viability was higher for porous structures than dense Ti, with evidence of pore-bridging by bacterial cells., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Titanium and alloys thereof are widely utilized for biomedical applications in the fields of orthopedics and dentistry. The corrosion resistance and perceived biocompatibility of such materials are essentially related to the presence of a thin passive oxide layer on the surface. However, during inflammation phases, the immune system and its leukocytic cells generate highly aggressive molecules, such as hydrogen peroxide and radicals, that can significantly alter the passive film resulting in the degradation of the titanium implants. In combination with mechanical factors, this can lead to the release of metal ions, nanoparticles or microscaled debris in the surrounding tissues (which may sustain chronic inflammation), bring about relevant health issues and contribute to implant loss or failure. After briefly presenting the context of inflammation, this review article analyses the state-of-the-art knowledge of the in vitro corrosion of titanium, titanium alloys and coated titanium by reactive oxygen species and by living cells with an emphasis on electrochemical and microstructural aspects. STATEMENT OF SIGNIFICANCE: Inflammation involves the production of reactive oxygen species that are known to alter the passive layer protecting titanium implants against the aggressive environment of the human body. Inflammatory processes therefore contribute to the deterioration of biomedical devices. Although review articles on biomaterials for implant applications are regularly published in the literature, none has ever focused specifically on the topic of inflammation. After briefly recalling the clinical context, this review analyses the in vitro studies on titanium corrosion under simulated inflammation conditions from the pioneer works of the 80s and the 90s till the most recent investigations. It reports about the status of this research area for a multidisciplinary readership covering the fields of materials science, corrosion and implantology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2021. Published by Elsevier Ltd.)

The mechanical stability and long-term success of an implant depends on the early healing phase and osseointegration of the bone around it. In addition, a healthy gingival tissue around the implant acts as a barrier that prevents bacteria and pathological byproducts from reaching the implant site. This study investigated the in-vitro attachment and spreading of human gingival fibroblasts (HGF) on bacterial grade polystyrene (PS) at different distances from radio-frequency glow-discharge (RFGD)-treated commercially pure titanium (cpTi) specimens. Controls included sterile cpTi specimens without RFGD treatment. A second set of experiments utilized media transferred to new bacterial grade polystyrene dishes (no cpTi) after the medium was conditioned by exposure to cpTi, either with or without RFGD treatment, for 24 hr. Surface characterization of the dishes was conducted through contact angle measurements and infrared spectroscopy. Cell numbers and surface areas were determined from Image J analysis of multiple microscopic images of fixed, stained cells. The results showed significantly greater numbers and surface areas on bacterial grade PS dishes at distances up to 15 mm from the RFGD-treated cpTi groups than for the controls. Moreover, a significant effect of the conditioned medium from RFGD-treated cpTi versus control cultures was shown on the numbers of fibroblasts attached to bacterial grade polystyrene dishes after 24 hr (p < 0.005) and 48 hr (p = 0.002) incubation. Surface areas of cells exposed to conditioned medium were not significantly different (p ≥ 0.05). Surface characterization of the PS dishes showed a higher value of the critical surface tensions of the treated group when compared to the control group., (© 2021 Wiley Periodicals LLC.)

Towards clinical translation of bioactive nano-engineered titanium implants, achieving appropriate sterilization and understanding its influence on the modified implant characteristics is essential. With limited studies exploring the influence of sterilization techniques on electrochemically anodized titanium with TiO 2 nanostructures, we aimed to advance this domain by performing an in-depth evaluation of the influence of common sterilization techniques (ethanol immersion, various UV irradiation times, gamma irradiation, and dry/wet autoclaving) on TiO 2 nanopores fabricated on micro-rough Ti surfaces (dual micro-nano) via single step anodization. Various sterilized surfaces were systematically compared in terms of topographical, chemical, crystalline, wettability and mechanical characteristics. Next, we investigated the protein adhesion capacity and functions of primary gingival fibroblasts (proliferation, adhesion/alignment and spreading morphology) to compare the bioactivity of the sterilized nanopores. Ethanol immersion, gamma irradiation and UV irradiation conserved the topography of the fabricated nanopores, while autoclave sterilization (both dry and wet) compromised the nanoporous structures. Various duration of UV-sterilization resulted in no significant changes in the surface topography and chemistry of the fabricated TNPs. Our findings revealed that UV irradiation is the most appropriate technique to sterilize nano-engineered titanium implants for appropriate wettability, protein adhesion capacity and enhanced metabolism and proliferation of human gingival fibroblasts (hGFs). This study systematically investigated the influence of sterilization on anodized nano-engineered titanium implants towards achieving reproducible outcomes (in terms of topography, chemistry and bioactivity), and found that UV irradiation holds great promise for application across different nano-engineered metal surfaces., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A variety of metallic biomaterials is used for fracture fixation. Allergic reactions towards nickel-containing steels urge the need for alternatives. The present study investigated the suitability of the nickel-free stainless steel P2000 in comparison to titanium alloy implants for bone surgical applications in a rabbit femora defect model. Thirty-six rabbits received two different cylindrical implants press-fit inserted into the distal femoral metaphysis. At day 0, 28, and 56, implant ingrowth was monitored by radiography; implant stability was assessed by pull-out torque measurements while bone-to-implant contact (BIC) was determined histomorphometrically. Radiography revealed comparable implant ingrowth after 1 and 2 months for both implant materials. The pull-out force of P2000 tended to be higher than that for titanium at day 28 (p = .076) but the values were comparable at day 56 (p = .905). At day 56, implant fixation was significantly increased compared to the day of surgery for both, P2000 (p = .030) and for titanium alloy (p = .026). Microscopic examination revealed that both implant types appeared to be well integrated and firmly anchored in the bone. BIC ratio of titanium alloy tended to be higher at day 28 (p = .079) but they did not differ significantly at day 56 (p = .711). In the present rabbit femora defect model, the nickel-free stainless steel P2000 provides primary stability and osseointegration comparable to that of titanium alloy implants., (© 2020 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals LLC.)

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 TiO 2 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Peri-implant infection after hip and knee arthroplasty is a common and serious complication. Titanium (Ti), polyethylene (PE), and Al 2 O 3 materials used as joint prosthesis materials have good biocompatibility and mechanical strength but no antibacterial effect. This study aimed to provide a theoretical basis for the design and manufacture of joint prosthesis materials with antibacterial effect. We applied a coating of gentamicin-silk protein (GS-Silk) on the surface of these materials. We characterized the Ti, PE, and Al 2 O 3 materials coated with GS-Silk (experimental group) and performed in vivo and in vitro experiments to test antibacterial activity. Scanning electron microscopy confirmed successful GS-Silk coating, and infrared spectroscopy confirmed successful loading of gentamicin onto the three materials. Nanoscratch test proved that the GS-Silk coating is relatively reliable on the surface of these three materials. The antibacterial effect of the coating in vitro and in vivo was verified by performing bacteriostatic ring test in vitro, bacterial adhesion test, and subendothelial implant infection test. We demonstrated that GS-Silk coating can effectively load gentamicin onto Ti, PE, and Al 2 O 3 materials and change the gentamicin release rate with a change in the solution pH to achieve intelligent release. The GS-Silk coating is relatively reliable on the surface of these three materials. Ti, PE, and Al 2 O 3 materials coated with GS-Silk have good antibacterial ability, both in vivo and in vitro., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Instrumentation during metastatic spine tumor surgery (MSTS) provides stability to the spinal column in patients with pathologic fracture or iatrogenic instability produced while undergoing extensive decompression. Titanium is the current implant material of choice in MSTS. However, it hinders radiotherapy planning and generates artifacts, with magnetic resonance imaging and computed tomography scans used for postoperative evaluation of tumor recurrence and/or complications. The high modulus of elasticity of titanium (110 GPa) results in stress shielding, which may lead to construct failure at the bone-implant interface. Polyether ether ketone (PEEK), a thermoplastic polymer, is an emerging alternative to titanium for use in MSTS. The modulus of elasticity of PEEK (3.6 GPa) is close to that of cortical bone (17-21 GPa), resulting in minimal stress shielding. Its radiolucent and nonmetallic properties cause minimal interference with magnetic resonance imaging and computed tomography scans. PEEK also causes low-dose perturbation for radiotherapy planning. However, PEEK has reduced bioactivity with bone and lacks sufficient rigidity to be used as rods in MSTS. The reduced bioactivity of PEEK may be addressed by 1) surface modification (introducing porosity or bioactive coating with hydroxyapatite [HA] or titanium) and 2) forming composites with HA/titanium. The mechanical properties of PEEK may be improved by forming composites with HA or carbon fiber. Despite these modifications, all PEEK and PEEK-based implants are difficult to handle and contour intraoperatively. Our review provides a comprehensive overview of PEEK and modified PEEK implants, with a description of their properties and limitations, potentially serving as a basis for their future development and use in MSTS., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Osteointegration is one of the most important factors for implant success. Several biomolecules have been used as part of drug delivery systems to improve implant integration into the surrounding bone tissue. Chemically modified mRNA (cmRNA) is a new form of therapeutic that has been used to induce bone healing. Combined with biomaterials, cmRNA can be used to develop transcript-activated matrices for local protein production with osteoinductive potential. In this study, we aimed to utilize this technology to create bone morphogenetic protein 2 (BMP2) transcript-activated coatings for titanium (Ti) implants. Therefore, different coating methodologies as well as cmRNA incorporation strategies were evaluated. Three different biocompatible biomaterials were used for the coating of Ti, namely, poly-d,l-lactic acid (PDLLA), fibrin, and fibrinogen. cmRNA-coated Ti disks were assayed for transfection efficiency, cmRNA release, cell viability and proliferation, and osteogenic activity in vitro . We found that cmRNA release was significantly delayed in Ti surfaces previously coated with biomaterials. Consequently, the transfection efficiency was greatly improved. PDLLA coating improved the transfection efficiency in a concentration-dependent manner. Lower PDLLA concentration used for the coating of Ti resulted in higher transfection efficiency. Fibrin and fibrinogen coatings showed even higher transfection efficiencies compared to all PDLLA concentrations. In those disks, not only the expression was up to 24-fold higher but also the peak of maximal expression was delayed from 24 h to 5 days, and the duration of expression was also extended until 7 days post-transfection. For fibrin, higher transfection efficiencies were obtained in the coatings with the lowest thrombin amounts. Accordingly, fibrinogen coatings gave the best results in terms of cmRNA transfection. All biomaterial-coated Ti surfaces showed improved cell viability and proliferation, though this was more noticeable in the fibrinogen-coated disks. The latter was also the only coating to support significant amounts of BMP2 produced by C2C12 cells in vitro . Osteogenesis was confirmed using BMP2 cmRNA fibrinogen-coated Ti disks, and it was dependent of the cmRNA amount present. Alkaline phosphatase (ALP) activity of C2C12 increased when using fibrinogen coatings containing 250 ng of cmRNA or more. Similarly, mineralization was also observed that increased with increasing cmRNA concentration. Overall, our results support fibrinogen as an optimal material to deliver cmRNA from titanium-coated surfaces.

From the past few years, developments of β-Ti alloys have been the subject of active research in the medical domain. The current paper highlights significant findings in the area of β-Ti alloy design, biological responses, strengthening mechanisms, and developing low-cost implants with a high degree of biocompatibility. It is evident that an astonishing demand for developing the low modulus-high strength implants can be fulfilled by synchronizing β stabilizer content and incorporating tailored thermo-mechanical techniques. Furthermore, the biological response of the implants is as important as the physical properties that regulate healing response; hence, the optimum selection of alloying elements plays a curial role for clinical success. The paper also presents the evolution of patents in this field from the year 2010 to 2020 showing the relevant innovations that may benefit a wide range of researchers., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The titanium implant was treated with plasma electrolytic oxidation and subsequent ionic exchange and thermal treatment in order to obtain bioactive layer consisting of titanium oxide, calcium and sodium titanates and hydroxyapatite, as confirmed by X-ray diffraction (XRD). Scanning electron microscopy (SEM) revealed that the given method, besides corresponding phase composition, enables suitable nanotopology for cell attachment and proliferation. Cytotoxicity investigations by MTT, LDH and propidium iodide assays and light microscopy showed that these coatings were not toxic to L929 cells.

Purpose of Review: New biomaterials for biomedical applications have been developed over the past few years. This work summarizes the current cell lines investigations regarding nanosurface modifications to improve biocompatibility and osseointegration., Recent Findings: Material surfaces presenting biomimetic morphology that provides nanoscale architectures have been shown to alter cell/biomaterial interactions. Topographical and biofunctional surface modifications present a positive effect between material and host response. Nanoscale surfaces on titanium have the potential to provide a successful interface for implantable biomedical devices. Future studies need to directly evaluate how the titanium nanoscale materials will perform in in vivo experiments. Biocompatibility should be determined to identify titanium nanoscale as an excellent option for implant procedures.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Graphene oxide (GO) and its derivatives are currently being explored for the modification of bone biomaterials. However, the effect of GO coatings on immunoregulation and subsequent impacts on osteogenesis are not known. In this study, GO was coated on pure titanium using dopamine. GO-coated titanium (Ti-GO) surfaces exhibited good biocompatibility, with the ability to stimulate the expression of osteogenic genes, and extracellular matrix mineralization in human mesenchymal stromal cells (hMSCs). Interestingly, it was found that GO-coated surfaces could manipulate the polarization of macrophages and expression of inflammatory cytokines via the Toll-like receptor pathway. Under physiological conditions, Ti-GO activated macrophages and induced mild inflammation and a pro-osteogenic environment, characterized by a slight increase in the levels of proinflammatory cytokines, as well as increased expression of the TGF-β1 and oncostatin M genes. In an environment mimicking acute inflammatory conditions, Ti-GO attenuated inflammatory responses, as shown by the downregulation of proinflammatory cytokines. Conditioned medium collected from macrophages stimulated by Ti-GO played a significant stimulatory role in the osteogenic differentiation of hMSCs. In summary, GO-coated surfaces displayed beneficial immunomodulatory effects in osteogenesis, indicating that GO could be a potential substance for the modification of bone scaffolds and implants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

We evaluated the effects of titanium plasma nitriding and oxidation on live endothelial cell viscoelasticity. For this, mechanically polished titanium surfaces and two surfaces treated by planar cathode discharge in nitriding (36N 2 and 24H 2 ) and oxidant (36O 2 and 24H 2 ). Surfaces were characterized regarding wettability, roughness and chemical composition. Rabbit aortic endothelial cells (RAECs) were cultured on the titanium surfaces. Cell morphology, viability and viscoelasticity were evaluated by scanning electron microscopy (SEM), methyl thiazolyl tetrazolium (MTT) assay and atomic force microscopy (AFM), respectively. Grazing Incidence X-ray Diffraction confirmed the presence of TiN 0,26 on the surface (grazing angle theta 1°) of the nitrided samples, decreasing with depth. On the oxidized surface had the formation of TiO 3 on the material surface (Theta 1°) and in the deeper layers was noted, with a marked presence of Ti (Theta 3°). Both plasma treatments increased surface roughness and they are hydrophilic (angle <90°). However, oxidation led to a more hydrophilic titanium surface (66.59° ± 3.65 vs. 76.88° ± 2.68; p = 0.001) due to titanium oxide films in their stoichiometric varieties (Ti 3 O, TiO 2 , Ti 6 O), especially Ti 3 O. Despite focal adhesion on the surfaces, viability was different after 24 h, as cell viability on the oxidized surface was higher than on the nitrided surface (9.1 × 10 3 vs. 4.5 × 10 3 cells; p < 0.05). This can be explained by analyzing the viscoelastic property of the cellular cytoskeleton (nuclear and peripheral) by AFM. Surface oxidation significantly increased RAECs viscoelasticity at cell periphery, in comparison to the nucleus (2.36 ± 0.3 vs. 1.5 ± 0.4; p < 0.05), and to the RAECs periphery in contact with nitrided surfaces (1.36 ± 0.7; p < 0.05) and polished surfaces (1.55 ± 0.6; p < 0.05). Taken together, our results have shown that titanium plasma treatment directly increased cell viscoelasticity via surface oxidation, and this mechanobiological property subsequently increased biocompatibility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Titanium dioxide (TiO 2 ) nanostructures are one of the most plentiful compounds that have emerged in various fields of technology such as medicine, energy and biosensing. Various TiO 2 nanostructures (nanotubes [NTs] and nanowires) have been employed in photoelectrochemical (PEC) biosensing applications, greatly enhancing the detection of targets. TiO 2 nanostructures, used as reinforced material or coatings for the bare surface of titanium implants, are excellent additive materials to compensate titanium implants deficiencies-like poor surface interaction with surrounding tissues-by providing nanoporous surfaces and hierarchical structures. These nanostructures can also be loaded by diversified drugs-like osteoporosis drugs, anticancer and antibiotics-and used as local drug delivery systems. Furthermore, TiO 2 nanostructures and their derivatives are new emerging antimicrobial agents to overcome human pathogenic microorganisms. However, like all other nanomaterials, toxicity and biocompatibility of TiO 2 nanostructures must be considered. This review highlights recent advances, along with the properties and numerous applications of TiO 2 -based nanostructure compounds in nano biosensing, medical implants, drug delivery and antibacterial fields. Moreover, in the present study, some recent advances accomplished on the pharmaceutical applications of TiO 2 nanostructures, as well as its toxicity and biocompatibility, are presented., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Jafari et al.)

Polymer-derived ceramics (PDC) have recently gained increased interest in the field of bioceramics. Among PDC's, carbon-rich silicon oxycarbide ceramics (SiOC) possess good combined electrical and mechanical properties. Their durability in aggressive environments and proposed cytocompatibility makes them an attractive material for fabrication of bio-MEMS devices such as pacemaker electrodes. The aim of the present study is to demonstrate the remarkable mechanical and electrical properties, biological response of PDCs modified with titanium (Ti) and their potential for application as pacemaker electrodes. Therefore, a new type of SiOC modified with Ti fillers was synthesized via PDC route using a Pt-catalyzed hydrosilylation reaction. Preceramic green bodies were pyrolyzed at 1000 °C under an argon atmosphere to achieve amorphous ceramics. Electrical and mechanical characterization of SiC x O 2(1- x ) /TiO x C y ceramics revealed a maximum electrical conductivity of 10 S cm -1 and a flexural strength of maximal 1 GPa, which is acceptable for pacemaker applications. Ti incorporation is found to be beneficial for enhancing the electrical conductivity of SiOC ceramics and the conductivity values were increased with Ti doping and reached a maximum for the composition with 30 wt % Ti precursor. Cytocompatibility was demonstrated for the PDC SiOC ceramics as well as SiOC ceramics modified with Ti fillers. Cytocompatibility was also demonstrated for SiTiOC20 electrodes under pacing conditions by monitoring of cells in an in vitro 3D environment. Collectively, these data demonstrate the great potential of polymer-derived SiOC ceramics to be used as pacemaker electrodes.

Various types of biodegradable polymers containing lactide, glycolide, caprolactone, and trimethylene carbonate units have been used to obtain ciprofloxacin (CFX)-enriched coatings developed on the Ti6Al7Nb alloy, intended for short-term therapy. In the first step, the surface of the Ti6Al7Nb alloy was modified, mostly according to sandblasting and anodic oxidation to obtain the TiO 2 layer. Anodizing can be an effective method for preparing TiO 2 coatings with osteoconductive properties. The polymer containing CFX molecules was deposited on the modified alloy, and Polymer + CFX/TiO 2 /Ti6Al7Nb systems were developed. CFX-enriched coatings adhered well to the surface of the previously modified alloy. Polymer layers maintain the topography of the alloy due to the development of the surface during the sandblasting method. As polymers intended for the study possess degradation ability, they are capable of releasing the incorporated drug. Antibacterial activity of CFX-enriched coatings was examined to verify the functionality of designed Polymer + CFX/TiO 2 /Ti6Al7Nb systems, and the bactericidal effect was confirmed for all cases. The presented study is an extension of previous, initial research and creates an overview of polyester or polyestercarbonate CFX-eluting coatings., (© 2020 Wiley Periodicals, Inc.)

Growing evidence suggests that the physical microenvironment can guide cell fate. However, cells sense cues from the adjacent physical microenvironment over a limited distance. In the present study, murine mesenchymal stem cells (MSCs) and murine preosteoblastic cells (MC3T3-E1) behaviors are regulated by the cell-material interface using ordered-micro and disordered-nano patterned structures on Ti implants. The optimal bone formation structure is a stable wave (horizontal direction: ridge, 2.7 µm; grooves, 5.3 µm; and vertical direction: distance, 700 µm) with the appropriate density of nano-branches (6.0 per µm 2 ). The repeated waves provide cells with directional guidance, and the disordered branches influence cell geometry by providing different spacing and density nanostructure. And micro-nano patterned structure can provide biophysical cues to direct cell phenotype development, including cell size, shape, and orientation, to influence cellular processes including survival, growth, and differentiation. Thus, the overlaid isotropic and anisotropic cues, ordered-micro and disordered-nano patterned structures, could transfer further and alter cell shape and induce nuclear orientation by activating Wnt/β-catenin signaling to promote integrin α5, integrin β1, cadherin 2, Runx2, Opn, and Ocn. That canonical Wnt signaling inhibitor dickkopf1 further demonstrates osteogenic differentiation induced by ordered-micro and disordered-nano patterned structures, which is related to Wnt/β-catenin signaling. Our findings show the role of ordered microstructures and disordered nanostructures in modulating stem cell differentiation with potential medical applications. STATEMENT OF SIGNIFICANCE: It remains a challenge to modify poor osteogenic and osteoconductive properties of titanium alloy bases on the inherent poverty of titanium. We demonstrate that ordered microtopography and disordered nano topography pattern structure could lead to osteogenic differentiation in vitro and bone regeneration in vivo. Furthermore, the pattern structure is created through selective laser melting and alkali heat. And the structure only takes advantage of titanium itself and does not bring in active film, such as hydroxyapatite. On the other hand, we find that cell shape and orientation show angle-orientation tendency due to the polarity, which involves with mechanical signal created via patterned structure. Meanwhile, the Wnt/Ca 2+ signaling pathway is activated., (Copyright © 2019. Published by Elsevier Ltd.)

Titanium (Ti) is that the most generally used material for dental, orthopedic and maxillofacial purposes thanks to its excellent biocompatibility and mechanical properties. Several data suggest that prosthesis anchorage to bone and soft tissue are often modulated by surface characteristics. Fibroblasts are the soft tissues cells concerned in producing extracellular matrix and collagen and their tight connection to implant neck is of paramount importance in preventing peri-implant infection. The aim of this work is to grow Human Fibroblast (HFb) for seven days in wells containing (or not) dental implants. The expression levels of some adhesion and traction-resistance related genes (COL11A1, COL2A1, COL9A1, DSP, ELN, HAS1, and TFRC) were analyzed using Polymerase Chain Reaction. Our results demonstrated that several genes encoding for extracellular matrix proteins are activated so giving more insight to the comprehension of the mechanism of cell to surface adhesion., (Copyright 2020 Biolife Sas. www.biolifesas.org.)

Objectives: The aim of this in vitro study was to assess changes in the gene expression of proinflammatory cytokines in human whole blood after contact with titanium implant surfaces conditioned by UV light. To this end, expression levels of proinflammatory cytokines were analyzed in vitro in human whole blood., Materials and Methods: Dental implants made of grade 4 titanium were conditioned by UV light in a UV device and submerged in human whole blood. Unconditioned implants served as controls, and blood samples without implants served as the negative control group. Sampling was performed at 1, 8, and 24 h. Changes in the expression levels of interleukin-1β (IL1B) and tumor necrosis factor alpha (TNF) were assessed using RT-qPCR at the mRNA level., Results: The gene expression of IL1B was significantly suppressed in the test group over the observation period compared to the control group during the 1-8 h after having contact between the implant surface and the blood. The gene expression of TNF was not significantly altered by UV conditioning after 1 and 8 h of observation, but both cytokine expression levels were increased significantly after 24 h., Conclusions: Differences in the gene expression of proinflammatory cytokines after insertion of UV-conditioned titanium implants can be assessed using a human whole blood test. UV-conditioned implant surfaces apparently suppress the release of IL1B in vitro., Clinical Relevance: The results of our publication demonstrate that modulation of the early inflammatory response in human whole blood is possible by surface treatment with UV light. In particular, the suppression of IL1B expression, especially after the initial contact of blood cells, may be beneficial in the osseointegration of titanium implants by positively influence the balance between rejection and acceptance of an implant.

A broad range of synthetic trabecular-like metallic lattices are 3D printed, to study the extra design freedom conferred by this new manufacturing process. The aim is to propose new conceptual types of implant structures for superior bio-mechanical matching and osseo-integration: synthetic bone. The target designs are 3D printed in Ti-6Al-4V alloy using a laser-bed process. Systematic evaluation is then carried out: (i) their accuracy is characterised at high spatial resolution using computed X-ray tomography, to assess manufacturing robustness with respect to the original geometrical design intent and (ii) the mechanical properties - stiffness and strength - are experimentally measured, evaluated, and compared. Finally, this new knowledge is synthesised in a conceptual framework to allow the construction of so-called implant design maps, to define the processing conditions of bone tailored substitutes, with focus on spine fusion devices. The design criteria emphasise the bone stiffness-matching, preferred range of pore structure for bone in-growth, manufacturability of the device and choice of inherent materials properties which are needed for durable implants. Examples of the use of such maps are given with focus on spine fusion devices, emphasising the stiffness-matching, osseo-integration properties and choice of inherent materials properties which are needed for durable implants. STATEMENT OF SIGNIFICANCE: We present a conceptual bio-engineering design methodology for new biomedical lattices produced by additive manufacturing, which addresses some of the critical points in currently existing porous implant materials. Amongst others: (i) feasibility and accuracy of manufacturing, (ii) design to the elastic properties of bone, and (iii) sensible pores sizes for osseointegration. This has inspired new and novel geometrical latticed designs which aim at improving the properties of intervertebral fusion devices. In their fundamental form, these structures are here fabricated and tested. When integrated into medical devices, these concepts could offer superior medical outcomes., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Integrating porous networks in load-bearing implants is essential in order to improve mechanical compatibility with the host tissue. Additive manufacturing has enabled the optimisation of the mechanical properties of metallic biomaterials, notably with the use of novel periodic regular geometries as porous structures. In this work, we successfully produced solid and lattice structures made of Ti-25Ta alloy with selective laser melting (SLM) using a Schwartz primitive unit-cell for the first time. The manufacturability and repeatability of the process was assessed through macrostructural and microstructural observations along with compressive testing. The mechanical properties are found to be suitable for bone replacement applications, showing significantly reduced elastic moduli, ranging from 14 to 36 GPa depending on the level of porosity. Compared to the conventionally used biomedical Ti-6Al-4V alloy, the Ti-Ta alloy offers superior mechanical compatibility for the targeted applications with lower elastic modulus, similar strength and higher ductility, making the Ti-25Ta alloy a promising candidate for a new generation of load-bearing implants., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Titanium-zirconium alloy (TiZr1317) is a new material used for biological implants. There are several studies on the effects of TiZr implants on the biological characteristics of human bone mesenchymal stem cells (hBMSCs)., Purpose: The purpose of this study was to investigate the biological responses of hBMSCs to implant holes affected by the physicochemical properties of oral implants (Ti SLA , Ti SLActive , TiZr SLA , and TiZr SLActive )., Materials and Methods: Grade 4 Ti and TiZr (13-17% Zr) substrates were modified by sand-blasted large-grit acid-etched (SLA) or hydrophilic sand-blasted large-grit acid-etched (SLActive), resulting in four types of surface with complex microstructures corresponding to the commercially-available implants SLA, RoxolidSLA, SLActive, and RoxolidSLActive (Institute Straumann AG, Basel, Switzerland). Physicochemical properties were detected and the biological responses of hBMSCs were observed., Results: Surface morphology characterization by scanning electron microscopy and atomic force microscopy revealed differences between the four groups. SLA ctive had higher surface energy/wettability than SLA, indicating that increased surface energy/wettability can promote the absorption of osteogenic proteins and enhance osseointegration. hBMSCs seeded on SLActive substrates exhibited better performance in terms of cell attachment, proliferation and osteoblastic differentiation than cells seeded on SLA., Conclusion: Because of their more suitable physicochemical properties, Ti SLActive and TiZr SLActive materials demonstrated more pronounced effects on the biological responses of hBMSCs compared with Ti SLA and TiZr SLA ., (© 2019 Wiley Periodicals, Inc.)

Molecular mechanism governing inflammatory scenario in response to titanium (Ti)-nanotexturing surfaces needs to be better addressed. Thus, we subjected pre-osteoblast to different Ti-texturing surfaces, as follows: machined (Mac), double acid-etching (DAE), and nanoscaled hydroxyapatite-blasted titanium surface (nHA), considering the cells chronically responding either directly (when the cells were cultured onto the surfaces) or indirectly (when the cells were challenged with the conditioned medium by the surfaces), up to 10 days. Our results showed that there is a dynamic requirement of inflammatory-related genes activation in response to nHA by up expressing IL1ß, IL6, IL10, and IL33 (direct condition) and IL6, IL10, IL18 (indirect condition). Importantly, our data show that there is inflammasome involvement, once NLRP3, ASC1, and CASP1 genes were also required. As we found a strong signal of IL10, an anti-inflammatory cytokine, we further investigated Sonic Hedgehog (Shh) signaling cascade. Surprisingly, Shh ligand and Smoothened (Smo) genes were up-modulated in response to nHA, while Patched (Ptc) was down-modulated. Finally, an interactome was built using bioinformatics reinforcing Shh signaling cascade on modulating IL10 transcripts by Src mediating this process and this prevalence of anti-inflammatory picture might explain the low profile of RANKL transcripts in response to nHA, compromising the osteoclastogenesis surrounding the implants. Taking our results into account, our data show that the inflammatory landscape promoted by nHA is strictly modulated by Shh signaling promoted anti-inflammatory pathways. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1597-1604, 2019., (© 2019 Wiley Periodicals, Inc.)

Additively manufactured selective laser melted titanium (SLM-Ti) opens the possibility of tailored medical implants for patients. Despite orthopedic implant advancements, significant problems remain with regard to suboptimal osseointegration at the interface between the implant and the surrounding tissue. Here, we show that applying a nanodiamond (ND) coating onto SLM-Ti scaffolds provides an improved surface for mammalian cell growth while inhibiting colonization of Staphylococcus aureus bacteria. Owing to the simplicity of our methodology, the approach is suitable for coating SLM-Ti geometries. The ND coating achieved 32 and 29% increases in cell density of human dermal fibroblasts and osteoblasts, respectively, after 3 days of incubation compared with the uncoated SLM-Ti substratum. This increase in cell density complements an 88% reduction in S. aureus detected on the ND-coated SLM-Ti substrata. This study paves a way to create facile antifouling SLM-Ti structures for biomedical implants.

Objectives: Using dental Ti implants has become a well-accepted and used method for replacing missing dentition. It has become evident that in many cases peri-implant inflammation develops. The objective was to create and evaluate the antibacterial effect of silver nanoparticle (Ag-NP) coated Ti surfaces that can help to prevent such processes if applied on the surface of dental implants. Methods: Annealing I, Ag ion implantation by the beam of an Electron Cyclotron Resonance Ion Source (ECRIS), Ag Physical Vapor Deposition (PVD), Annealing II procedures were used, respectively, to create a safely anchored Ag-NP layer on 1x1 cm 2 Grade 2 titanium samples. The antibacterial effect was evaluated by culturing Staphylococcus aureus (ATCC 29213) on the surfaces of the samples for 8 hours, and comparing the results to that of glass as control and of pure titanium samples. Alamar Blue assay was carried out to check cytotoxicity. Results: It was proved that silver nanoparticles were present on the treated surfaces. The average diameter of the particles was 58 nm, with a 25 nm deviation and Gaussian distribution, the the filling factor was 25%. Antibacterial evaluation revealed that the nanoparticle covered samples had an antibacterial effect of 64.6% that was statistically significant. Tests also proved that the nanoparticles are safely anchored to the titanium surface and are not cytotoxic. Conclusion: Creating a silver nanoparticle layer can be an option to add antibacterial features to the implant surface and to help in the prevention of peri-implant inflammatory processes. Recent studies demonstrated that silver nanoparticles can induce pathology in mammal cells, thus safe fixation of the particles is essential to prevent them from getting into the circulation., Competing Interests: The authors report no conflicts of interest in this work.