Additively manufactured Ti–Ta–Cu alloys for the next-generation load-bearing implants

Bacterial colonization of orthopedic implants is one of the leading causes of failure and clinical complexities for load-bearing metallic implants. Topical or systemic administration of antibiotics may not offer the most efficient defense against colonization, especially in the case of secondary infection, leading to surgical removal of implants and in some cases even limbs. In this study, laser powder bed fusion was implemented to fabricate Ti3Al2V alloy by a 1:1 weight mixture of CpTi and Ti6Al4V powders. Ti-Tantalum(Ta)–Copper(Cu) alloys were further analyzed by the addition of Ta and Cu into the Ti3Al2V custom alloy. The biological,mechanical, and tribo-biocorrosion properties of Ti3Al2V alloy were evaluated. A 10 wt.% Ta(10Ta) and 3 wt.% Cu(3Cu) were added to the Ti3Al2V alloy to enhance biocompatibility and impart inherent bacterial resistance. Additively manufactured implants were investigated for resistance against Pseudomonas aeruginosa and Staphylococcus aureus strains of bacteria for up to 48 h. A 3 wt.% Cu addition to Ti3Al2V displayed improved antibacterial efficacy, i.e.78%–86% with respect to CpTi. Mechanical properties for Ti3Al2V–10Ta–3Cu alloy were evaluated, demonstrating excellent fatigue resistance, exceptional shear strength, and improved tribological and tribo-biocorrosion characteristics when compared to Ti6Al4V. In vivo studies using a rat distal femur model revealed improved early-stage osseointegration for alloys with10 wt.% Ta addition compared to CpTi and Ti6Al4V. The 3 wt.% Cu-added compositions displayed biocompatibility and no adverse infammatory response in vivo. Our results establish the Ti3Al2V–10Ta–3Cu alloy’s synergistic effect on improving both in vivo biocompatibility and microbial resistance for the next generation of load-bearing metallic implants.

HVOF-sprayed HAp/S53P4 BG composite coatings on an AZ31 alloy for potential applications in temporary implants

Bioactive thermal spray coatings produced via high-velocity oxygen fuel spray(HVOF)from hydroxyapatite(HAp)and bioactive glasses(BG)have the potential to be employed on temporary implants due to the ability of both HAp and BG to dissolve and promote osseointegration,considering that both phases have different reaction and dissolution rates under in-vitro conditions.In the present work,75%wt.HAp-25%wt.S53P4 bioactive glass powders were HVOF-sprayed to obtain HAp/S53P4 BG composite coatings on a bioresorbable AZ31 alloy.The study is focused on exploring the effect of the stand-off distance and fuel/oxygen ratio variation as HVOF parameters to obtain stable structural coatings and to establish their effect on the phases and microstructure produced in those coatings.Different characterization techniques,such as scanning electron microscopy,X-ray diffraction,and Fourier transform infrared spectroscopy,were employed to characterize relevant structural and microstructural properties of the composite coatings.The results showed that thermal gradients during coating deposition must be managed to avoid delamination due to the high temperature achieved(max 550℃)and the differences in coefficients of thermal expansion.It was also found that both spraying distance and oxygen/fuel ratio allowed to keep the hydroxyapatite as the main phase in the coatings.In addition,in-vitro electrochemical studies were performed on the obtained HAp/S53P4 BG composite coatings and compared against the uncoated AZ31 alloy.The results showed a significant decrease in hydrogen evolution(at least 98%)when the bioactive coating was applied on the Mg alloy during evaluation in simulated body fluid(SBF).

Review on the Fabrication of Surface Functional Structures for Enhancing Bioactivity of Titanium and Titanium Alloy Implants

Titanium and its alloys have been widely applied in many biomedical fields because of its excellent mechanical properties,corrosion resistance and good biocompatibility.However,problems such as rejection,shedding and infection will occur after titanium alloy implantation due to the low biological activity of titanium alloy surface.The structures with specific functions,which can enhance osseointegration and antibacterial properties,are fabricated on the surface of titanium implants to improve the biological activity between the titanium implants and human tissues.This paper presents a comprehensive review of recent developments and applications of surface functional structure in titanium and titanium alloy implants.The applications of surface functional structure on different titanium and titanium alloy implants are introduced,and their manufacturing technologies are summarized and compared.Furthermore,the fabrication of various surface functional structures used for titanium and titanium alloy implants is reviewed and analyzed in detail.Finally,the challenges affecting the development of surface functional structures applied in titanium and titanium alloy implants are outlined,and recommendations for future research are presented.

Complicated calcified alloplastic implants in the nasal dorsum:A clinical analysis

BACKGROUND In rhinoplasty,calcification around silicone implants is frequently observed in the tip dorsum(TD)area.Additionally,based on a review of various literature,it is presumed that calcification in silicone implants occurs due to both inflammatory chemical reactions and physical friction against the tissue.The calcification of nasal silicone implants not only results in the functional loss of the implants,but also leads to material deformation.However,there is a lack of research on calcification of nasal silicone implants in the current literature.AIM To elucidate various clinical characteristics of calcification around nasal silicone implants,using histological and radiological analysis.METHODS This study analyzed data from 16 patients of calcified nasal implants,who underwent revision rhinoplasty for various reasons after undergoing augmentation rhinoplasty with silicone implants.The collected data included information on implant duration,implant types,location of calcification,presence of inflammatory reactions,and computed tomography(CT)scans.RESULTS The most common location of calcification,as visually analyzed,was in the TD area,accounting for 56%.Additionally,the analysis of CT scans revealed a trend of increasing Hounsfield Unit values for calcification with the duration of implantation,although this trend was not statistically significant(P=0.139).CONCLUSION Our study shows that reducing the frequency of calcification may be achievable by using softer silicone implants and by minimizing the damage to perioperative tissues.

Elimination of methicillin‑resistant Staphylococcus aureus biofilms on titanium implants via photothermally‑triggered nitric oxide and immunotherapy for enhanced osseointegration

Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0.01).In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs,but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype(P<0.05 or P<0.01).The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways(P<0.01).In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model(P<0.01).Conclusions:Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.

In vivo and in vitro study of resorbable magnesium wires for medical implants:Mg purity,surface quality,Zn alloying and polymer coating

Magnesium is an excellent material in terms of biocompatibility and its corrosion products can serve as an active source for new bone formation.However,localized corrosion and H_(2)generation limit the potential of Mg-based implants.Utilizing low-alloyed Mg-Zn wires can strongly reduce problems with large H_(2)bubbles and improve the mechanical properties considerably while maintaining excellent long-term biocompatibility.Acidic pickling and a polymer coating can be effectively used to lower the rate of in vivo degradation.In this work,microstructural,mechanical,and in vitro characterization of 250μm and 300μm extruded wires made from ultra-pure Mg,commercially pure Mg,Mg-0.15Zn,Mg-0.4Zn and Mg-1Zn was performed.Additionally,Mg-0.4Zn wires together with a variant coated with a copolymer of L-lactide andε-caprolactone were tested in vivo on artificially damaged Wistar rat femurs.Based on the observed Mg-induced osteogenesis,polymer-coated Mg wires with a small addition of Zn are a perspective material for bone-support applications,such as cerclage and fixation wires.

Porous metal implants: processing,properties, and challenges

Porous and functionally graded materials have seen extensive applications in modern biomedical devices—allowing for improved site-specific performance;their appreciable mechanical,corrosive,and biocompatible properties are highly sought after for lightweight and high-strength load-bearing orthopedic and dental implants.Examples of such porous materials are metals,ceramics,and polymers.Although,easy to manufacture and lightweight,porous polymers do not inherently exhibit the required mechanical strength for hard tissue repair or replacement.Alternatively,porous ceramics are brittle and do not possess the required fatigue resistance.On the other hand,porous biocompatible metals have shown tailorable strength,fatigue resistance,and toughness.Thereby,a significant interest in investigating the manufacturing challenges of porous metals has taken place in recent years.Past research has shown that once the advantages of porous metallic structures in the orthopedic implant industry have been realized,their biological and biomechanical compatibility—with the host bone—has been followed up with extensive methodical research.Various manufacturing methods for porous or functionally graded metals are discussed and compared in this review,specifically,how the manufacturing process influences microstructure,graded composition,porosity,biocompatibility,and mechanical properties.Most of the studies discussed in this review are related to porous structures for bone implant applications;however,the understanding of these investigations may also be extended to other devices beyond the biomedical field.

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.

Long-term complications of the transmeatal approach (Open Transcanal) in cochlear implants: A follow-up study

Objective: Multiple alternative approaches of cochlear implant surgery have been described, such as the suprameatal approach, transcanal approach, transmeatal approach and middle cranial fossa approach.Transmeatal(open trnascanal) approach has not been adapted since first described in the clinical field.we aimed to assess the long-term complications of the transmeatal approach in a series of 131 patients at our center between 2004 and 2008.Methods: This study was a retrospective case series of all patients who underwent cochlear implants with the transmeatal(open transcanal) approach from May 2004 to December 2008 at King Faisal Specialist and Research Hospital(Riyadh, Saudi Arabia), which were conducted by the same surgeon.Results: Complications were observed often with various combinations-recurrent otitis externa, posterior tympanic membrane perforation, electrode extrusion, cholesteatoma, and chronic mastoiditis. The overall long-term complication rate was 16%(21/131). The gap between the implantation and the diagnosis of a complication ranged from <1 year to 11 years. Major complications were as follows:cholesteatoma in 5(3.8%) patients, extrusion of the electrode in 5(3.8%) patients, and tympanic membrane perforation or deep retractions in 5(3.8%) patients. Minor complications were as follows: recurrent mastoiditis with/without concomitant temporary facial nerve palsy in 4(3%) patients, recurrent otitis externa infections in 7(5%) patients, and weakness of the posterior canal wall in 1 patient.Conclusion: The transmeatal approach posed an high rate of complications on long-term follow-up such as cholestetoma formation, extrusion of electrode or perielectrode reaction formation to tympanic membrane and external auditory canal.

Complications Related to the Insertion Technique of Jadelle® Contraceptive Implants

Introduction: Contraceptive implants are one of the most effective methods of birth spacing. Jadelle® implants consist of two strands that are easy to insert and remove. Although their effectiveness is no longer in question, their use (insertion) requires a surgical procedure with the corollary possibility of complications. These are mainly insertions that are too deep (in the arm muscle), vascular and nerve damage. Material and Methods: Our study focused on complications related to implant insertion. It was a descriptive and retrospective study over thirty-four months, from October 2016 to July 2019, and concerned all patients seen in consultation and who presented a complication related to the insertion of contraceptive implants in the Department of Gynecology and Obstetrics of the National Hospital of Pikine. Results: We collected nine complications managed at the Gynecology and Obstetrics Department of the Centre Hospitalier National de Pikine from 2016 to 2019. These were insertions that were too deep with sometimes nerve damage, infection or incident during anesthesia. The operative procedures were based on the type of complication. Conclusion: Although Jadelle® has the advantage of having only 2 rods compared to its predecessor Norplant®, its use is also conditioned by insertion and removal procedures which may experience complications.

Actual Practical Attitude and Knowledge of Dental Implants among Senior Dental Students and General Dentists Graduated from Some Saudi and Non-Saudi Dental Schools

Objective: To assess the actual practical attitude and knowledge of dental implants among senior dental students and general dentists graduated from some Saudi and Non-Saudi dental schools. Methods: A total of 300 senior dental students and general dentists participated in the study. Hard copies of the self-designed, multiple-choice questionnaires were distributed to all participants. The questionnaire consisted of 31 questions in five parts. Data were collected and analyzed using Chi-square test and t-test, where p Results: There is a statistically significant relationship between the participants’ answers, and their dental schools. Participants’ general knowledge, training, and teaching of dental implants, as well as information about restorations retained for the dental implants, were higher among participants from Saudi dental schools than participants from non-Saudi dental schools, while the information about dental implants was higher among participants from non-Saudi dental schools than participants from Saudi dental schools. Conclusion: We conclude that the actual practical attitude and knowledge of dental implants among participants in the current study was insufficient. Therefore, dental implant education in the undergraduate curricula of dental schools surveyed should be updated to include teaching, laboratory training, and preclinical and clinical training.

Targeted hyperalkalization with NaOH-loaded starch implants enhances doxorubicin efficacy in tumor treatment

High-alkali treatment using sodium hydroxide(NaOH)injection can be a therapeutic approach for killing tumor cells.Alkalization can damage cellular structures and lead to cell death.Increased alkalinity can also enhance the efficacy of certain chemotherapeutic drugs such as doxorubicin(DOX).In this study,NaOH-loaded starch implants(NST implants)were used to induce hyperalkalization(increase pH)in the tumor environment,thereby inducing necrosis and enhancing the effects of DOX.NaOH is a strongly alkaline substance that can increase the pH when injected into a tumor.However,the administration of NaOH can have toxic side effects because it increases the pH of the entire body,not just at the tumor site.To overcome this problem,we developed an injectable NST implant,in which NaOH can be delivered directly into the tumor.This study showed that NST implants could be easily administered intratumorally in mice bearing 4T1 tumors and that most of the NaOH released from the NST implants was delivered to the tumors.Although some NaOH from NST implants can be systemically absorbed,it is neutralized by the body’s buffering effect,thereby reducing the risk of toxicity.This study also confirmed both in vitro and in vivo that DOX is more effective at killing 4T1 cells when alkalized.It has been shown that administration of DOX after injection of an NST implant can kill most tumors.Systemic absorption and side effects can be reduced using an NST implant to deliver NaOH to the tumor.In addition,alkalinization induced by NST implants not only exerts anticancer effects but can also enhance the effect of DOX in killing cancer cells.Therefore,the combination of NaOH-loaded starch implants and DOX treatment has the potential to be a novel therapy for tumors.

Stress Distributions Created by Short and Regular Implants Placed in the Anterior Maxilla at Different Angles: A Finite Element Analysis

Although short implants are seen as alternative treatments that require additional surgical techniques in posterior region, they can be applied to anterior maxilla and various studies are required on this subject. The purpose of this study was to examine and compare the peak von Mises stress distributions in the crown, implant and abutment by using finite element analysis (FEA). Besides, a comparison of the implant-abutment connection types in the short implant with the FEA method was established. A short implant (4 × 5 mm) with a taper-lock connection and a regular implant (4 × 9 mm) with a screw connection were used in maxillary central incisor tooth area. Three different titanium abutments with 0?, 15? and 25? angles were used for abutments. In addition, in order to determine whether the stress change in short implants is due to the length of the implant-abutment connection, a screw was designed for a short implant and it was also evaluated in the same three angles. A total of three groups and nine models were generated. 114.6N load was applied to the cingulum area of the crown at an angle of 135? to the long axis of the crowns. A torque load of 25 Ncm was applied to the regular and short implant screw. Von Mises stress distributions of implants, abutments and crowns were evaluated by using FEA. Increased angle in implants increased von Mises stress values of implant, abutment and crown. Screw connection was found higher at all angles in short implants. Close values were found at different angles in taper-lock short implant crowns. The length and the angle in the bone of implant with the type of implant-abutment connection results in the accumulated stress values. Clinical Implications Taper implant-abutment connection system was found to be more promising in terms of stress accumulation in crowns. Although the amount of stress on the abutment increased due to the length of the implant in short implants, taper implant-abutment connection system slightly reduced related to this increase.

Evaluation of Novel Chitosan Based Composites Coating on Wettability for Pure Titanium Implants

This work aims to prepare chitosan(CS)-based coated layers,CS(10 wt%nanosilver/90 wt%CS,10 wt%biotin/90 wt%CS,and 5 wt%nanosilver–5 wt%biotin)/90 wt%CS coatings are prepared,onto pure Ti substrate.The surface morphology of the novel CS composite coating was studied using field emission scanning electron microscopy,atomic force microscopy(AFM),Fourier transforms infrared(FTIR)and wettability test.Results show that the addition of(biotin,nanosilver)5 Vol.%improves the properties of composite materials.Using different particles’scale size aid in improving the combinations in the alginate,producing a dual effect on film properties.Coating surface roughness decreased in the chitosan-based biocomposite with preferable homogeneity and crack-free coating layers,as confirmed by AFM.An increase in surface roughness ensured substitution,which enhanced the surface structures.The high wettability of the CS-based coating layers was due to the presence of nanoparticles,and the composite coatings with CS,nanosilver,or biotin had excellent wettability because of the good hydrophilic nature of the CS matrix combined with reinforced particles.The FTIR results showed that peaks of the blending of CS plus nanoparticles,CS plus biotin,or CS plus nanosilver plus biotin were excellent matching with no changes in the structure of the matrix.

Deep brain implantable microelectrode arrays for detection and functional localization of the subthalamic nucleus in rats with Parkinson’s disease

The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.

Alginate/gelatin/boron-doped hydroxyapatite-coated Ti implants:in vitro and in vivo evaluation of osseointegration

In this study,boron-doped hydroxyapatite(BHT)-loaded alginate/gelatin-based(A/G)hydrogel coating on Ti was fabricated to support bone integration through triggering osteoinduction,vascularization and immunomodulation.Initially,highly reproducible,cheap and time-effective BHT was produced,which significantly promoted higher osteogenic and angiogenic maturation,while a mild innate immune response was observed.The immense potential of BHT was evidenced by the production of a gap-filling A/G/BHT interphase on Ti implants to mimic the osseous extracellular matrix to achieve functional bridging and exert control over the course of innate immune response.We initially aminosilanized the implant surface using 3-aminopropyl triethoxysilane,and then coated it with 0.25%w/v alginate with 20 mM 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide to allowthe A/G/BHT pre-gel to disperse evenly and covalently attach on the surface.The pre-gel was added with 0.2 M NaCl to homogeneously blend BHT in the structure without inducing ionic crosslinking.Then,the coated implants were freeze-dried and stored.The coated layer demonstrated high cohesive and adhesive strength,and 8-month-long shelf-life at room temperature and normal humidity.The A/G/BHT was able to coat an irregularly shaped Ti implant.Osteoblasts and endothelial cells thrived on the A/G/BHT,and it demonstrated greatly improved osteogenic and angiogenic capacity.Moreover,A/G/BHT maintained macrophage viability and generated an acute increase in immune response that could be resolved rapidly.Finally,A/G/BHT was shown to induce the robust integration of implant in a rabbit femur osteochondral model within 2months.Therefore,we concluded that A/G/BHT coatings could serve as amultifunctional reservoir,promoting the strong and rapid osseointegration of metallic implants.

Nasal implants for drug delivery:Advancements and applications

Nasal implants have emerged as a pioneering technology for nasal drug delivery systems.These are breakthrough options made of biocompatible materials that are temporarily inserted into the nasal passages for both functional and cosmetic purposes.Drug-eluting nasal implants are beneficial for improving patient compliance,reducing the need for repeated drug administration,and achieving controlled release of therapeutic agents.This article offers a comprehensive insight into nasal implants and their applications,and addresses a patent perspective in the same context.Important considerations for clinically approved implants,such as Propel,Sinuva,Sinu-Foam,and Relieva Stratus,have also been discussed.

The role of exosomes in bone remodeling and osseointegration of implants

Dental implant is an effective method in the treatment of missing teeth.The process of osseointegration of implant teeth involves the coordinated operation of immune system and bone system.The interaction between cells is closely related to bone formation and repair.Exosomes are important intercellular communication molecules.They were originally found in the supernatant of sheep erythrocytes cultured in vitro.They are micro vesicles with a diameter of 40~150 nm.They exist in a variety of cells and body fluids.They enter the target cells by endocytosis and transport,affecting the expression of cell genes and changing the fate of cells.It has an important regulatory function in the microenvironment of implant bone binding.It plays a role in bone remodeling through small molecular RNA,specific proteins and other growth factors secreted by different cells.This article reviews the role of bone derived cellderived exosomes in bone remodeling and their function in implant osseointegration.

Accelerated fracture healing by osteogenic Ti45Nb implants through the PI3K–Akt signaling pathway

The key to managing fracture is to achieve stable internal fixation,and currently,biologically and mechanically appropriate internal fixation devices are urgently needed.With excellent biocompatibility and corrosion resistance,titanium–niobium alloys have the potential to become a new generation of internal fixation materials for fractures.However,the role and mechanism of titanium–niobium alloys on promoting fracture healing are still undefined.Therefore,in this study,we systematically evaluated the bone-enabling properties of Ti45Nb via in vivo and in vitro experiments.In vitro,we found that Ti45Nb has an excellent ability to promote MC3T3-E1 cell adhesion and proliferation without obvious cytotoxicity.Alkaline phosphatase(ALP)activity and alizarin red staining and semiquantitative analysis showed that Ti45Nb enhanced the osteogenic differentiation of MC3T3-E1 cells compared to the Ti6Al4V control.In the polymerase chain reaction experiment,the expression of osteogenic genes in the Ti45Nb group,such as ALP,osteopontin(OPN),osteocalcin(OCN),type 1 collagen(Col-1)and runt-related transcription factor-2(Runx2),was significantly higher than that in the control group.Meanwhile,in the western blot experiment,the expression of osteogenic-related proteins in the Ti45Nb group was significantly increased,and the expression of PI3K–Akt-related proteins was also higher,which indicated that Ti45Nb might promote fracture healing by activating the PI3K–Akt signaling pathway.In vivo,we found that Ti45Nb implants accelerated fracture healing compared to Ti6Al4V,and the biosafety of Ti45Nb was confirmed by histological evaluation.Furthermore,immunohistochemical staining confirmed that Ti45Nb may promote osteogenesis by upregulating the PI3K/Akt signaling pathway.Our study demonstrated that Ti45Nb exerts an excellent ability to promote fracture healing as well as enhance osteoblast differentiation by activating the PI3K/Akt signaling pathway,and its good biosafety has been confirmed,which indicates its clinical translation potential.

Impact of High Sodium Diet on Neovascularization and Osseointegration around Titanium Implant:An in Vivo and in Vitro Study

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.