Ti Implants Research Articles

NSUN2 methylates IRF4 to affect the capacity of macrophages attached to titanium implant on osteogenic differentiation of PDLSCs and angiogenesis of HUVECs in vitro.

We aimed to investigate the effect and underlying mechanism of titanium (Ti) implant on the polarization of macrophages and subsequent effects on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and angiogenesis of human umbilical vein endothelial cells (HUVECs) affected by macrophages. Firstly, the regulatory effect of Ti implant on macrophage polarization was investigated. Levels of M1 polarization markers and M2 polarization markers in macrophages were evaluated by immunofluorescence staining method and qPCR analysis. The osteogenic differentiation capacity of PDLSCs cultured with supernatants of macrophages of each group was evaluated by the Alizarin Red S (ARS) staining method and qPCR. Angiogenesis related genes were also evaluated in HUVECs cultured in supernatants of macrophages. To explore whether RNA m5C modification can modulate the effects of Ti implant on macrophage regulation of osteogenic differentiation and angiogenesis, we analyzed the main genes related to m5C in macrophages using RNA m5C dot blotting and qPCR methods. The interaction between NSUN2 and IRF4 was verified by m5C-RIP, RIP, and double-luciferase gene report experiments. Macrophages were activated as M1 macrophages under the interference of LPS, and macrophages attached to Ti implants were more easily activated as M2 macrophages under the action of LPS. Macrophages activated by Ti implant enhanced osteogenic differentiation of PDLSCs and angiogenesis of HUVECs. NSUN2 level was up-regulated in macrophages treated with LPS and was down-regulated by Ti implant. Over-expression of NSUN2 attenuated the effect of Ti implant on M1 polarization promotion of macrophages and enhanced the M2 polarization promotion of macrophages. Up-regulation of NSUN2 weakened the effects of Ti implant on promotion the capacity of macrophages on osteogenic differentiation of PDLSCs and angiogenesis of HUVECs. The KEGG analysis suggested that IRF4 was enriched in several inflammatory signaling pathways. Moreover, NSUN2 methylates IRF4 to affect the capacity of macrophages on osteogenic differentiation of PDLSCs and angiogenesis of HUVECs. Taken together, macrophages of M1 type can be stimulated by Ti implants in vitro, promoting osteogenic differentiation of PDLSCs and angiogenesis in HUVECs through NSUN2-mediated methylation of IRF4.

Tissue-Safe Low-Temperature Plasma Treatment for Effective Management of Mature Peri-Implantitis Biofilms on Titanium Surfaces.

The unique screw-shape design and microstructure of implants pose a challenge for mechanical debridement in removing biofilms. Biofilms exhibit increased resistance to antimicrobials relative to single planktonic cells, emphasizing the need for effective biofilm removal during periodontal therapy for peri-implantitis treatment. To tackle this issue, our team evaluated the effectiveness of low-temperature plasma (LTP) for disinfecting titanium discs contaminated with multispecies biofilms associated with peri-implantitis, specifically focusing on biofilms matured for 14 and 21 days as well as biofilms that had formed on StraumannⓇ Ti-SLA implants for 21 days. The biofilms included Actinomyces naeslundii, Porphyromonas gingivalis, Streptococcus oralis, and Veillonella dispar, which were grown in anaerobic conditions. These biofilms were subjected to LTP treatment for 1, 3, and 5 min, using distances of 3 or 10 mm from the LTP nozzle to the samples. Control groups included biofilms formed on Ti discs or implants that received no treatment, exposure to argon flow at 3 or 10 mm of distance for 1, 3, or 5 min, application for 1 min of 14 μg/mL amoxicillin, 140 μg/mL metronidazole, or a blend of both, and treatment with 0.12% chlorhexidine (CHX) for 1 min. For the implants, 21-day-old biofilms were treated with 0.12% CHX 0.12% for 1 min and LTP for 1 min at a distance of 3 mm for each quadrant. Biofilm viability was assessed through bacterial counting and confocal laser scanning microscopy. The impact of LTP was investigated on reconstituted oral epithelia (ROE) contaminated with P. gingivalis, evaluating cytotoxicity, cell viability, and histology. The results showed that a 1 min exposure to LTP at distances of 3 or 10 mm significantly lowered bacterial counts on implants and discs compared to the untreated controls (p < 0.017). LTP exposure yielded lower levels of cytotoxicity relative to the untreated contaminated control after 12 h of contamination (p = 0.038), and cell viability was not affected by LTP (p ≥ 0.05); thus, LTP-treated samples were shown to be safe for tissue applications, with low cytotoxicity and elevated cell viability post-treatment, and these results were validated by qualitative histological analysis. In conclusion, the study's results support the effectiveness of 1 min LTP exposure in successfully disinfecting mature peri-implantitis multispecies biofilms on titanium discs and implants. Moreover, it validated the safety of LTP on ROE, suggesting its potential as an adjunctive treatment for peri-implantitis.

Electrophoretic deposition of curcumin-loaded mesoporous bioactive glass nanoparticle-chitosan composite coatings on titanium for treating tumor-induced bone defect

Clinical treatment of osteosarcoma (OS) presents significant challenges in postoperative tumor recurrence and large segmental bone defects, often necessitating joint replacement or artificial bone implantation to repair failed or defective bone tissue. At the same time, fibroblastic encapsulation can impede direct contact between implants and bones, leading to implant failure. To tackle these issues, mesoporous bioactive glass nanoparticles (MBN) were synthesized and then loaded with curcumin (CUR). Subsequently, chitosan (CTS) was chosen as the charger and coating matrix, and electrophoretic deposition (EPD) was utilized to fabricate a CTS-MBN-CUR composite coating with triple functionality on Ti implants aiming for OS-induced bone repair. MBN-CUR nanoparticles are encapsulated in CTS and uniformly distributed within the coating, achieving robust adhesion and long-term release of CUR. Concurrently, the developed CTS-MBN-CUR coating exhibits moderate hydrophilicity, and good bioactivity. Moreover, three different types of cells, MC3T3-E1, L929, and MG63 cells, were individually cultured with the composite coating and subjected to comprehensive cellular studies. The coating presented favorable bioactivities, and osteogenic performance, and the ability to resist the activity of fibroblast and OS cells. These findings suggest that CTS-MBN-CUR holds promising potential for bone regeneration following OS resection surgery.

Influence of titanium nanoparticles on cytotoxicity and inflammatory cytokines expression in gingival fibroblasts - An in vitro study

Background Despite the success of titanium (Ti) implants in dental rehabilitation, emerging evidence implicates the release of titanium oxide nanoparticles (TiO2NPs) from the implant surface as a potential contributor to the initiation of the pathogenic process leading to peri-implantitis and ultimately failure of the implants. However, a comprehensive investigation to elucidate the dose-dependent effects of TiO2NPs on cytotoxicity and inflammatory responses is lacking. The present study was undertaken to evaluate the effect of different concentrations of TiO2NPs on the cytotoxicity and inflammatory cytokine expression in Human Gingival Fibroblasts (HGFs). Methods HGFs were isolated from gingival tissue samples obtained from periodontally and systemically healthy subjects. Ti standard solution for ICP was diluted to create concentrations of (0.001 ppm, 0.01 ppm, 0.1 ppm, 1 ppm, 10 ppm, and 100 ppm) for cell culture media containing titanium. HGFs were then cultured in these varying concentrations for specific time periods (days 1, 3, 5, and 7) to assess cell viability. A cytotoxicity assay was performed to determine the levels and expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and anti-inflammatory cytokines (IL-10, IL-12, TGF-β) using qRT-PCR and ELISA techniques. Results Our findings demonstrate a concentration and duration-dependent decrease in HGF viability upon exposure to titanium nanoparticles. Notably, a 50% reduction in cell viability was observed at the highest concentration (100 ppm). qRT-PCR analysis revealed a significant upregulation of pro-inflammatory cytokines, particularly IL-1β and IL-6, in HGFs exposed to titanium. Interestingly, the expression of anti-inflammatory cytokines (IL-10, IL-12, and TGF-β) remained comparable or even equivalent compared to controls across different titanium concentrations. Conclusions The study revealed a concentration and duration-dependent influence on HGF viability and cytokine profile, suggesting potential cytotoxicity and modulation of the inflammatory response mediated by TiO2NPs. Further research is necessary to elucidate the underlying mechanisms and their implications for dental implant biocompatibility.

Enhancing Bone-Titanium integration through hydrogel coating mediated sequential M1/M2 polarization of interfacial macrophages

Regulating phenotypes of in situ macrophages (Mφ) is a cutting-edge strategy for promoting bone-Titanium (Ti) integration, but what is the most rational modulation manner has long been controversial. Short-term inducing in situ M1 Mφ polarization or inducing in situ M2 Mφ polarization have proven to be capable of promoting osseointegration. However, an increasing number of researches have claimed that sequentially inducing in situ M1/M2 Mφ polarization, compared to the above-mentioned two strategies, could further enhance osseointegration. In this work, we compared the capability of the three different modulation manners to promote osseointegration. Briefly, we anchored a homogeneous Poly(HEMA-co-3APBA)/LUT/SOP hydrogel coating, which could sequentially release pro-inflammatory sophoridine (SOP) molecules and anti-inflammatory luteolin (LUT) molecules through pH mediated conformational transition of phenylboronic acid ester bonds, on the surface of Ti implants. Ti implants coated with the Poly(HEMA-co-3APBA)/SOP hydrogel or the Poly(HEMA-co-3APBA)/LUT hydrogel, which merely released SOP molecules and LUT molecules respectively, were utilized as controls. In vitro Mφ co-culture assays proved the immunoregulation functions of different hydrogel coatings in inducing Mφ polarization, and the rationale behind which was identified to be related to the PI3K-AKT signaling pathways. In addition, the immunoregulation mediated osteogenic differentiation behaviors of bone marrow mesenchymal stem cells (BMSCs) were also investigated. Implantation of as-prepared Ti nails to a rat femur defect model followed by evaluations of H&E staining, Masson staining, immunohistochemical staining, etc. proved the stronger capability to enhance osseointegration of inducing sequential M1/M2 Mφ polarization than short-term inducing in situ M1 Mφ polarization or inducing in situ M2 Mφ polarization. This work not only reported a novel Ti implant with superior osseointegration capability but also will inspire corresponding researches in the future.

Effect of MoS₂/polydopamine coating on surface properties and biocompatibility of Ti implants

Effect of MoS₂/polydopamine coating on surface properties and biocompatibility of Ti implants

Enhanced osteointegration and osteogenesis of osteoblast cells by laser-induced surface modification of Ti implants

Dental and orthopedic implants have become routine medical technologies for tooth replacement and bone fixation. Despite significant progress in implantology, achieving sufficient osseointegration remains a challenge, often leading to implant failure over the long term. Nanotechnology offers the potential to mimic the natural patterns of living tissues, providing a promising platform for tissue engineering and implant surface design. Among the various methods for developing nanostructures, High-Regular Laser-Induced Periodic Surface Structures (HR-LIPSS) techniques stand out for their ability to fabricate highly ordered nanostructures with excellent long-range repeatability and production efficiency. In this study, we utilized an innovative technical approach to generate traditional laser-induced superficial LIPSS nanostructures, followed by detailed surface analysis using classical microscopy and physicochemical methods. Our findings demonstrate for the first time that nanostructured LIPSS surfaces can significantly enhance cell adhesion and proliferation while providing an optimal environment for cell metabolism. Given the high reproducibility, low cost, and potential of HR-LIPSS techniques to support cell growth and differentiation, this novel technology has the potential to impact both the industrial development of new implants and clinical outcomes after implantation.

Inflammatory or Reparative? Tuning Macrophage Polarization Using Anodized Anisotropic Nanoporous Titanium Implant Surfaces

Modulating macrophage phenotype based on implant surface characteristics, including topography and chemistry, has been employed to enhance osseointegration and long‐term functional outcomes for titanium (Ti)‐based implants. An excessive and/or prolonged M1 macrophage response can lead to damaging immune‐inflammatory reactions, negatively influencing the fate of the implant, and hence, modulating these responses via nanoscale implant surface modification is an emerging paradigm. Herein, an anodized titanium implant surface based on single‐step electrochemical anodization, with preserved underlying microfeatures and superimposed nanopores (50 and 70 nm), compared with irregular rough and microrough (machined‐like) surfaces, is investigated for its effect on the functions of primary macrophages in vitro. Significantly reduced macrophage proliferation and increased tissue‐reparative M2 phenotype polarization are confirmed for the nanopores, which are more pronounced for 70 nm diameter. Moreover, osteoclastogenesis is reduced while osteogenic differentiation of osteoblasts is enhanced for the nanopores (higher for 70 nm pores). Advanced nanoengineered Ti implants can enhance titanium implant tissue integration by modulating the inflammatory response at the implant–cell interface.

Evaluation of biocompatibility and osseointegration of multi-component TiAl6V4 titanium alloy implants.

This study aimed to investigate the biocompatibility and osseointegration of novel titanium (Ti) implants with a perforated part with high surface roughness (Ra >4 μm) and a smooth solid part (test group), as compared to smooth solid Ti implants (control group; Ra < 0.8 μm). Test and control implants were implanted in rabbit femurs. After 4 and 15 weeks, host tissue reaction and quality of tissue formed were evaluated with histopathology, while micro-CT scans were used to quantitatively assess bone-implant contact (BIC), surrounding bone formation, and bone ingrowth. After 4 and 15 weeks, minimal host reaction was found in the test group. Histopathological analysis showed new bone formation around the implants in both the test and control groups after 4 weeks. Furthermore, additional bone growth was often observed within the holes of the test implants. After 15 weeks, the test implants showed high bone ingrowth and the presence of mature bone in direct contact with the implant surface, whereas, bone ingrowth was poorer for the control group with 30% of the control implants, showing larger gaps at the bone-implant interface. Quantitative micro-CT analysis revealed comparable BIC and bone formation in both groups at 4 weeks, but higher BIC and more bone formation in the test group than in the control group after 15 weeks. No significant differences were observed in any of the analyses. In conclusion, partially perforated, high-roughness Ti implants showed excellent osseointegration and minimal host reaction, indicating their potential for orthopedic applications in bone repair and regeneration.

Adoptive transfer of immunomodulatory macrophages reduces the pro-inflammatory microenvironment and increases bone formation on titanium implants

Macrophages play a central role in orchestrating the inflammatory response to implanted biomaterials and are sensitive to changes in the chemical and physical characteristics of the implant. Macrophages respond to biological, chemical, and physical cues by polarizing into pro-inflammatory (M1) or anti-inflammatory (M2) states. We previously showed that rough-hydrophilic titanium (Ti) implants skew macrophage polarization towards an anti-inflammatory phenotype and increase mesenchymal stem cell (MSC) recruitment and bone formation around the implant. In the present study, we aimed to investigate whether the adoptive transfer of macrophages in different polarization states would alter the inflammatory microenvironment and improve biomaterial integration in macrophage-competent and macrophage-ablated mice. We found that ablating macrophages increased the presence of neutrophils, reduced T cells and MSCs, and compromised the healing and biomaterial integration process. These effects could not be rescued with adoptive transfer of naïve or polarized macrophages. Adoptive transfer of M1 macrophages into macrophage-competent mice increased inflammatory cells and inflammatory microenvironment, resulting in decreased bone-to-implant contact. Adoptive transfer of M2 macrophages into macrophage-competent mice reduced the pro-inflammatory environment in the peri‑implant tissue and increased bone-to-implant contact. Taken together, our results show the importance of macrophages in controlling and modulating the inflammatory process in response to implanted biomaterials and suggest they can be used to improve outcomes following biomaterial implantation. Statement of significanceMacrophages are central in orchestrating the inflammatory response to implanted biomaterials and are sensitive to biomaterial chemical and physical characteristics. Our study shows that a deficiency of macrophages results in prolonged inflammation and abolishes bone-biomaterial integration. Adoptive transfer of immunomodulatory macrophages into macrophage-competent mice reduced the inflammatory environment and increased bone-implant contact.

Hyperbranched Poly-l-Lysine Modified Titanium Surface With Enhanced Osseointegration, Bacteriostasis, and Anti-Inflammatory Properties for Implant Application: AnExperimental InVivo Study.

This study aimed to explore multiple effects of hyperbranched poly-l-lysine (HBPL) titanium (Ti) surfaces on osseointegration, bacteriostasis, and anti-inflammation across three different animal models. Ti surfaces were covalently modified with HBPL, with uncoated surfaces as controls. Characterization included scanning electron microscopy (SEM) and surface chemistry and elemental analysis (EDX). Ti and Ti-HBPL implants were placed in conventional canine edentulous sites, post-operative infection canine edentulous sites, and diabetic rat tibias. Implants from canine edentulous models were analyzed using micro-CT and histomorphometry to assess osseointegration at 8 weeks. Post-operative infection beagles were used to evaluate antibacterial efficacy through clinical parameters and bacterial cultures at 1 week. In diabetic rats, micro-CT and histomorphometry were performed at 8 weeks. HBPL was uniformly grafted on Ti-HBPL surfaces. Ti-HBPL surfaces showed higher bone volume/total volume (BV/TV, p < 0.001), bone-implant contact (BIC%, p < 0.001), and trabecular number (Tb.N, p < 0.01) in beagles. Besides, it displayed higher BIC% (p < 0.001) and bone area fraction occupancy (BAFO%, p < 0.01) in hard tissue sections. In an infected model, Ti-HBPL surfaces exhibited lower bleeding on probing (BOP, p < 0.001), and plaque index (DI, p < 0.01), with reduced bacterial colony formation (p < 0.001) compared to the control group. In diabetic rats, Ti-HBPL surfaces showed an increase in BV/TV (p < 0.01) and Tb.N (p < 0.001), downregulated TNF-α and IL-1β (p < 0.01), and upregulated IL-10 (p < 0.01) and osteocalcin (OCN) expression (p < 0.01). HBPL-Ti surfaces demonstrated enhanced osseointegration, bacteriostasis, and anti-inflammatory effects invivo.

Micro-arc driven porous ZrO2 coating for tailoring surface properties of titanium for dental implants application

Titanium (Ti) is an ideal material for dental implants due to its excellent properties. However, corrosion and mechanical wear lead to Ti ions and particles release, triggering inflammatory responses and bone resorption. To overcome these challenges, surface modification techniques are used, including micro-arc oxidation (MAO). MAO creates adherent, porous coatings on Ti implants with diverse chemical compositions. In this context, zirconia element stands out in its wear and corrosion properties associated with low friction and chemical stability. Therefore, we investigated the impact of adding zirconium oxide (ZrO2) to Ti surfaces through MAO, aiming for improved electrochemical and mechanical properties. Additionally, the antimicrobial and modulatory potentials, cytocompatibility, and proteomic profile of surfaces were investigated. Ti discs were divided into four groups: machined – control (cpTi), treated by MAO with 0.04 M KOH – control (KOH), and two experimental groups incorporating ZrO2 at concentrations of 0.04 M and 0.08 M, composing the KOH@Zr4 and KOH@Zr8 groups. KOH@Zr8 showed higher surface porosity and roughness, even distribution of zirconia, formation of crystalline phases like ZrTiO4, and hydrophilicity. ZrO2 groups showed better mechanical performance including higher hardness values, lower wear area and mass loss, and higher friction coefficient under tribological conditions. The formation of a more compact oxide layer was observed, which favors the electrochemical stability of ZrO2 surfaces. Besides not inducing greater biofilm formation, ZrO2 surfaces reduced the load of pathogenic bacteria evidenced by the DNA-DNA checkerboard analysis. ZrO2 surfaces were cytocompatible with pre-osteoblastic cells. The saliva proteomic profile, evaluated by liquid chromatography coupled with tandem mass spectrometry, was slightly changed by zirconia, with more proteins adsorbed. KOH@Zr8 group notably absorbed proteins crucial for implant biological responses, like albumin and fibronectin. Incorporating ZrO2 improved the mechanical and electrochemical behavior of Ti surfaces, as well as modulated biofilm composition and provided suitable biological responses.

Crystallographic plane-induced selective mineralization of nanohydroxyapatite on fibrous-grained titanium promotes osteointegration and biocorrosion resistance

The (002) crystallographic plane-oriented hydroxyapatite (HA) and anatase TiO2 enable favorable hydrophilicity, osteogenesis, and biocorrosion resistance. Thus, the crystallographic plane control in HA coating and crystalline phase control in TiO2 is vital to affect the surface and interface bioactivity and biocorrosion resistance of titanium (Ti) implants. However, a corresponding facile and efficient fabrication method is absent to realize the HA(002) mineralization and anatase TiO2 formation on Ti. Herein, we utilized the predominant Ti(0002) plane of the fibrous-grained titanium (FG Ti) to naturally form anatase TiO2 and further achieve a (002) basal plane oriented nanoHA (nHA) film through an in situ mild hydrothermal growth strategy. The formed FG Ti-nHA(002) remarkably improved hydrophilicity, mineralization, and biocorrosion resistance. Moreover, the nHA(002) film reserved the microgroove-like topological structure on FG Ti. It could enhance osteogenic differentiation through promoted contact guidance, showing one order of magnitude higher expression of osteogenic-related genes. On the other hand, the nHA(002) film restrained the osteoclast activity by blocking actin ring formation. Based on these capacities, FG Ti-nHA(002) improved new bone growth and binding strength in rabbit femur implantation, achieving satisfactory osseointegration within 2 weeks.

Creating an extracellular matrix-like three-dimension structure to enhance the corrosion resistance and biological responses of titanium implants

Background/purposeTitanium (Ti) is extensively used in dental and orthopedic implants due to its excellent mechanical properties. However, its smooth and biologically inert surface does not support the ingrowth of new bone, and Ti ions may have adverse biological effects. The purpose is to improve the corrosion resistance of titanium and create a 3D structured coating to enhance osseointegration through a very simple and fast surface treatment. Materials and methodsThis study investigated the use of sandblasting, acid etching, and NaOH leaching to produce porous Ti implants with enhanced biological activity and corrosion resistance. ResultsThese surface modifications generated a mixed oxide layer resembling the extracellular matrix (ECM), consisting of a dense amorphous TiO2 inner layer (50–100 nm thick) and a TiO2 outer layer with interconnected pores (pore size 50–500 nm; 150–200 nm thick). The inner layer significantly improved corrosion resistance, while the hydrophilic outer layer, with its porous structure, facilitated protein albumin adsorption and promoted the attachment, proliferation, and mineralization of human bone marrow mesenchymal stem cells. ConclusionThe combined surface treatment approach of sandblasting, acid etching, and NaOH leaching offers a comprehensive solution to the challenges associated with titanium implants' biological inertness and corrosion susceptibility. By enhancing both the biological activity and corrosion resistance of Ti surfaces, this protocol holds significant promise for improving dental and orthopedic implants' success rates and longevity. Future studies should focus on in vivo assessments and long-term clinical trials to further validate these findings and explore the potential for widespread clinical adoption.

Enhancing osseointegration and angiogenesis of Titanium implants through KMnO4-Modified Montmorillonite nano-clay coating

Titanium (Ti) is a widely used and favored material for dental implants, with research efforts focusing on enhancing its osseointegration capabilities. Montmorillonite (MMT), a nano-clay, has shown significant potential in drug delivery, wound healing, and other biomedical applications. Implant coatings based on MMT have demonstrated promising results; however, challenges remain in terms of surface bond strength, stability, and uniformity. Studies have indicated that manganese (Mn) can enhance cell viability, proliferation, and adhesion by activating integrin receptors. Here, a KMnO4-modified MMT (MAO-MMT-Mn) coating was developed on Ti through the micro-arc oxidation (MAO) technique. The MAO-MMT-Mn coating significantly strengthens its bond, enabling it to withstand greater loads. The incorporation of Mn, silicon (Si) and phosphorus (P) resulted in the formation of uniformly distributed lamellar MMT, facilitating the sustained release of these elements. In vitro experiments demonstrated that the MAO-MMT-Mn coating promoted osteoblast adhesion and endothelial cell migration, and led to a significant increase in the expression of osteogenic and angiogenic genes compared to uncoated Ti. Moreover, in vivo assessments using micro-CT scans and histological staining revealed improved local osseointegration and angiogenesis after 4 weeks of implantation. In conclusion, the MAO-MMT-Mn coating offers a safe, simple, and cost-effective method to enhance the surfaces of Ti implants, thereby potentially enhancing the clinical outcomes of dental implant procedures.

"Photo-Thermo-Electric" Dental Implant for Anti-Infection and Enhanced Osteoimmunomodulation.

The dental implant market has experienced explosive growth, owing to the widespread acceptance of implants as the core of oral rehabilitation. Clinically, achieving simultaneous anti-infective effects and rapid osseointegration is a crucial but challenging task for implants. The demand for implants with long-term broad-spectrum antibacterial and immune-osteogenic properties is growing. Existing methods are limited by a lack of safety, efficiency, short-lasting anti-infective ability, and inadequate consideration of the immunomodulatory effects on osteogenesis. Herein, a ZnO/black TiO2-x heterojunction surface structure was designed as a near-infrared (NIR) light-responsive nanofilm immobilized on a titanium (Ti) implant surface. This nanofilm introduces abundant oxygen vacancies and heterojunctions, which enhance the photothermal and photoelectric abilities of Ti implants under NIR illumination by narrowing the band gap and improving interfacial charge transfer. The "photo-thermo-electric" implant exhibits excellent broad-spectrum antibacterial efficacy against three dental pathogenic bacteria (Porphyromonas gingivalis, Fusobacterium nucleatum, and Staphylococcus aureus, >99.4%) by destroying the bacterial membrane and increasing the production of intracellular reactive oxygen species. Additionally, the implant can effectively eliminate mature multispecies biofilms and kill bacteria inside the biofilms under NIR irradiation. Meanwhile, this implant can also induce the pro-regenerative transformation of macrophages and promote osteoblast proliferation and differentiation. Moreover, in vivo results confirmed the superior antibacterial and osteoimmunomodulatory properties of this dental implant. RNA sequencing revealed that the underlying osteogenic mechanisms involve activation of the Wnt/β-catenin signaling pathway and bone development. Overall, this versatile "photo-thermo-electric" platform endows implants with anti-infection and bone integration performance simultaneously, which holds great potential for dental implants.

Self-adhesive poly-l-lysine/tannic acid hybrid hydrogel for synergistic antibacterial activity against biofilms

Biomedical implants are crucial for enhancing various human physiological functions. However, they are susceptible to microbial contamination after implantation, posing a risk of implant failure. To address this issue, hydrogel-based coatings are used, but achieving both effective antibacterial properties and stable adhesion remains challenging. This study introduces a hybrid hydrogel network made from Tannic Acid (TA) and Poly-l-Lysine (PLL), cross-linked through ionic and hydrogen bonds, which imparts adhesive and anti-infective properties. The physicochemical analysis revealed that the hydrogels exhibited significant porosity, favorable mechanical characteristics, and demonstrated in vitro enzymatic biodegradation. Moreover, the hydrogels demonstrated adhesion to various substrates, including Ti alloy with an adhesive strength of 42.5 kPa, and retained their integrity even after immersion in water for a minimum of 10 days. The modified Ti surfaces significantly reduced protein adsorption (∼70 %), indicating antifouling properties. The hydrogels prevented bacterial adhesion on titanium surfaces through a “contact-kill” mode of action and inhibited biofilm formation by around 94.5 % for Staphylococcus aureus and 90.8 % for Pseudomonas aeruginosa. The modified Ti retained biofilm inhibitory effects for at least six days without significant performance decline. In vitro cytotoxicity assay confirmed the biocompatibility of the hydrogels with NIH3T3 cells. Overall, these results highlight the competence of hybrid hydrogels as effective coatings for Ti implants, offering strong adhesion and biofilm prevention to mitigate implant-related infections.

Implant Design and Cervical Spinal Biomechanics and Neurorehabilitation: A Finite Element Investigation.

The cervical spine, pivotal for mobility and overall body function, can be affected by cervical spondylosis, a major contributor to neural disorders. Prevalent in both general and military populations, especially among pilots, cervical spondylosis induces pain and limits spinal capabilities. Anterior Cervical Discectomy and Fusion (ACDF) surgery, proposed by Cloward in the 1950s, is a promising solution for restoring natural cervical curvature. The study objective was to investigate the impacts of ACDF implant design on postsurgical cervical biomechanics and neurorehabilitation outcomes by utilizing a biofield head-neck finite element (FE) platform that can facilitate scenario-specific perturbations of neck muscle activations. This study addresses the critical need to enhance computational models, specifically FE modeling, for ACDF implant design. We utilized a validated head-neck FE model to investigate spine-implant biomechanical interactions. An S-shaped dynamic cage incorporating titanium (Ti) and polyetheretherketone (PEEK) materials was modeled at the C4/C5 level. The loading conditions were carefully designed to mimic helmet-to-helmet impact in American football, providing a realistic and challenging scenario. The analysis included intervertebral joint motion, disk pressure, and implant von Mises stress. The PEEK implant demonstrated an increased motion in flexion and lateral bending at the contiguous spinal (C4/C5) level. In flexion, the Ti implant showed a modest 5% difference under 0% activation conditions, while PEEK exhibited a more substantial 14% difference. In bending, PEEK showed a 24% difference under 0% activation conditions, contrasting with Ti's 17%. The inclusion of the head resulted in an average increase of 18% in neck angle and 14% in C4/C5 angle. Disk pressure was influenced by implant material, muscle activation level, and the presence of the head. Polyetheretherketone exhibited lower stress values at all intervertebral disc levels, with a significant effect at the C6/C7 levels. Muscle activation level significantly influenced disk stress at all levels, with higher activation yielding higher stress. Titanium implant consistently showed higher disk stress values than PEEK, with an orders-of-magnitude difference in von Mises stress. Excluding the head significantly affected disk and implant stress, emphasizing its importance in accurate implant performance simulation. This study emphasized the use of a biofidelic head-neck model to assess ACDF implant designs. Our results indicated that including neck muscles and head structures improves biomechanical outcome measures. Furthermore, unlike Ti implants, our findings showed that PEEK implants maintain neck motion at the affected level and reduce disk stresses. Practitioners can use this information to enhance postsurgery outcomes and reduce the likelihood of secondary surgeries. Therefore, this study makes an important contribution to computational biomechanics and implant design domains by advancing computational modeling and theoretical knowledge on ACDF-spine interaction dynamics.

Modified Titanium Implants Satisfy the Demands of Diabetic Osseointegration via Sequential Regulation of Macrophages and Mesenchymal Stem Cells.

The application of titanium (Ti) implants for patients with diabetes mellitus (DM) is still facing a significant challenge due to obstacles such as hyperglycemia, reactive oxygen species (ROS), and chronic inflammation, which hinders osseointegration. To address this issue, a Ti implant with dual functions of regulating polarization of macrophages and facilitating osseointergration is developed via hydrothermal reaction and hydrogel coating. The reactive oxygen species (ROS) and glucose (Glu) responsive hydrogel coating can locally deliver adenosine (ADO) in the early stage of implantation. The controlled release of ADO regulated the phenotype of macrophages, restored oxidative balance, and enhanced mitochondrial function during the early stages of implantation. Subsequently, strontium (Sr) ions will be released to promote osteogenic differentiation and proliferation of mesenchymal stem cells (MSCs), as the hydrogel coating degraded. It eventually leads to bone reconstruction during the late stages, aligning with the biological cascade of bone healing. The modified Ti implants showed effective osteogenesis for bone defects in DM patients, shedding light on the design and biological mechanisms of surface modification. This research offers promising potential for improving the treatment of bone-related complications in diabetic patients.

Design and development of titanium-coated implants with advanced antioxidant properties for enhanced regenerative repair of diabetic bone

The aging population is closely associated with chronic metabolic diseases, including diabetes, hypertension, and other metabolic disorders. Metabolic dysfunction is a primary characteristic of diabetic patients, which can impair cellular response to insulin and lead to increased production of reactive oxygen species (ROS), hindering bone healing. Therefore, the development of multifunctional titanium (Ti) implants with the ability to eliminate reactive oxygen and promote bone formation is the optimal strategy to address this issue. In this study, we designed a thioctic acid(Ta) coating loaded with strontium(Sr), forming a strong bond with the Ti implant (Ti-Ta@Sr). During treatment, sulfuric acid demonstrated the ability to release monomers in the early stages, effectively eliminating excess reactive oxygen produced in high-glucose environments and regulating the diabetic microenvironment. The delayed in-situ release of strontium ions also enhanced osteogenic differentiation efficiency. Both in vivo and in vitro experiments confirmed that Ti-Ta@Sr significantly restored the osteogenic capacity and proliferation of osteoblasts under high-glucose conditions. These advantages make Ti-Ta@Sr a promising candidate material for orthopedic implants, suitable for repairing bone defects in diabetic patients.