Bimetallic Gold/Silver and Bioactive Camptothecin Hybrid Nanoparticles for Eradication of Cancer Stem Cells in a Combination Manner.

The defeat of cancer is still a challenge due to the existence of cancer stem cells (CSCs) because they resist conventional chemotherapy via multifactor regulated mechanisms. Consequently, one-dimensional action toward CSCs cannot work. Herein, we used rationally designed hybrid nanoparticles as a combined cancer therapy, hoping to form a multidimensional control network. In this paper, gold/silver alloy nanoparticle decorated camptothecin nanocrystals were formulated according to complementary anti-CSC mechanisms from gold, silver, and organic drug. This smart drug formulation could combine chemotherapy and thermotherapy, target different tumor sites, and demonstrate versatile toxicity profiles from each component. Major results indicated that this nanosystem demonstrated indiscriminately effective cytotoxic/proapoptotic/necrotic activity against bulk MCF-7 cells and their CSC subpopulation, in particular under laser ablation. Moreover, this nanosystem displayed enhanced antineoplastic activity against CSC spheroids, resulting in a significant reduction in their number and size, that is, their self-renewal capacity. All the results indicated that CSCs upon treatment of these new hybrid nanoparticles underwent reduced stemness and conversion from the original quiescent state and recovered their sensitivity toward chemotherapy. The relevant anticancer mechanism was ascribed to NIR-pH dual responsive drug release, synergistic/combined thermo-chemotherapy of organic drug and inorganic alloy nanoparticles, enhanced cellular uptake mediated by alloy nanoparticles, and Ag+-induced biomembrane damage. This thermo-chemotherapy platform provides a new combinatorial strategy for inorganic and organic agents in the complete elimination of CSCs.

Enhancing Bactericidal Properties of Ti6Al4V Surfaces through Micro and Nano Hierarchical Laser Texturing.

Orthopedic and dental implants made from Ti6Al4V are widely used due to their excellent mechanical properties and biocompatibility. However, the long-term performance of these implants can be compromised by bacterial infections. This study explores the development of hierarchically textured surfaces with enhanced bactericidal properties to address such challenges. Hierarchical surface structures were developed by combining microscale features produced by a microsecond laser and superimposed submicron features produced using a femtosecond laser. Microscale patterns were produced by the pulsed laser surface melting process, whereas submicrometer laser-induced periodic surface structures were created on top of them by femtosecond laser processing. Escherichia coli bacterial cells were cultured on the textured surface. After 24 h, a staining analysis was performed using SYTO9 and PI dyes to investigate the samples with a confocal microscope for live dead assays. Results showed bacterial colony formation onto the microscale surface textures with live bacterial cells, whereas the hierarchical surface textures display segregated and physically damaged bacterial cell attachments on surfaces. The hierarchical surface textures showed ∼98% dead bacterial cells due to the combined effect of its multiscale surface features and oxide formation during the laser processing steps. The efficacy of hierarchical surface textures in enhancing the antibacterial behavior of Ti6Al4V implants is evident from the conducted research. Such laser-based surface treatments can find potential applications in different industrial sectors.

Investigation of the Relationship between Surface Features, Protein Adsorption, and Osteoimmunomodulation: The Case of a Chemically Treated Titanium Alloy.

This paper deals with the combined effects of immune response and osseointegration because of the lack of comprehensive studies on this topic. An antibacterial Ti surface was considered because of the high risk of infection for titanium bone implants. A chemically treated Ti6Al4 V alloy [Ti64(Sr-Ag)] with a microporous and Sr-Ag doped surface was compared to a polished version (Ti64) regarding protein adsorption (albumin and fibronectin) and osteoimmunomodulation. Characterization via fluorescence microscopy and zeta potential showed a continuous fibronectin layer on Ti64(Sr-Ag), even with preadsorbed albumin, while it remained filamentous on Ti64. Macrophages (differentiated from THP-1 monocytes) were cultured on both surfaces, with viability and cytokine release analyzed. Differently from Ti64, Ti64(Sr-Ag) promoted early anti-inflammatory responses and significant downregulation of VEGF. Ti64(Sr-Ag) also enhanced human bone marrow mesenchymal cell differentiation toward osteoblasts, when a macrophage-conditioned medium was used, influencing ALP production. Surface properties in relation to protein adsorption and osteoimmunomodulation were discussed.

Black phosphorus-incorporated novel Ti-12Mo-10Zr implant for multimodal treatment of osteosarcoma.

The repair and reconstruction of large bone defects after bone tumor resection is still a great clinical challenge. At present, orthopedic implant reconstruction is the mainstream treatment for repairing bone defects. However, according to clinical feedback, local tumor recurrence and nonunion of bone graft are common reasons leading to the failure of bone defect repair and reconstruction after bone tumor resection, which seriously threaten the physical and mental health of patients. On this basis, here the self-developed low modulus Ti-12Mo-10Zr alloy (TMZ) was chosen as substrate material. To improve its biological activity and osteointegration, calcium, oxygen, and phosphorus co-doped microporous coating was prepared on TMZ alloy by microarc oxidation (MAO). Then, black phosphorus (BP) nanosheets were incorporated onto MAO treated TMZ alloy to obtain multifunctional composites. The obtained BP-MAO-TMZ implant exhibited excellent photothermal effects and effective ablation of osteosarcoma cancer cells under the irradiation of 808 nm near infrared laser, while no photothermal or therapeutic effects were observed for TMZ alloy. Meanwhile, the structure/component bionic coating obtained after MAO treatment as well as the P-driven in situ biomineralization performance after incorporation of BP nanosheets endowed BP-MAO-TMZ implant with synergistic promoting effect on MC3T3-E1 osteoblasts' activity, proliferation and differentiation ability. This study is expected to provide effective clinical solutions for problems of difficult bone regeneration and tumor recurrence after tumor resection in patients with bone tumors and to solve a series of medical problems such as poor prognosis and poor postoperative quality of patients life with malignant bone tumors.

Design and preparation of Ti-xFe antibacterial titanium alloys based on micro-area potential difference.

Fe was selected as an alloying element for the first time to prepare a new antibacterial titanium alloy based on micro-area potential difference (MAPD) antibacterial mechanism. The microstructure, the corrosion resistance, the mechanical properties, the antibacterial properties and the cell biocompatibility have been investigated in detail by optical microscopy, scanning electron microscopy, electrochemical testing, mechanical property test, plate count method and cell toxicity measurement. It was demonstrated that heat treatment had a significant on the compressive mechanical properties and the antibacterial properties. Ti-xFe (x = 3,5 and 9) alloys after 850 °C/3 h + 550 °C/62 h heat treatment exhibited strong antimicrobial properties with an antibacterial rate of more than 90% due to the MAPD caused by the redistribution of Fe element during the aging process. In addition, the Fe content and the heat treatment process had a significant influence on the mechanical properties of Ti-xFe alloy but had nearly no effect on the corrosion resistance. All Ti-xFe alloys showed non-toxicity to the MC3T3 cell line in comparison with cp-Ti, indicating that the microzone potential difference had no adverse effect on the corrosion resistance, cell proliferation, adhesion, and spreading. Strong antibacterial properties, good cell compatibility and good corrosion resistance demonstrated that Ti-xFe alloy might be a candidate titanium alloy for medical applications.

Enhanced Antimicrobial Activity of AgCu Nanoparticles: The Role of Particle Size and Alloy Composition.

AgCu bimetallic· nanoparticles (NPs) represent a novel class of inorganic, broad-spectrum antimicrobial agents that offer enhanced antimicrobial effectiveness and reduced cytotoxicity compared to conventional Ag NP antibacterial materials. This study examines the antimicrobial performance and structural characteristics of AgCu nanoparticles (NPs) synthesized via two distinct chemical reduction processes using PVP-PVA as stabilizers. Despite identical chemical elements and sphere-like shapes in both synthesis methods, the resulting AgCu nanoparticles exhibited significant differences in size and antimicrobial properties. Notably, AgCu NPs with smaller average particle sizes demonstrated weaker antimicrobial activity, as assessed by the minimum inhibitory concentration (MIC) measurement, contrary to conventional expectations. However, larger average particle-sized AgCu NPs showed superior antimicrobial effectiveness. High-resolution transmission electron microscopy analysis revealed that nearly all larger particle-sized nanoparticles were AgCu nanoalloys. In contrast, the smaller particle-sized samples consisted of both AgCu alloys and monometallic Ag and Cu NPs. The fraction of Ag ions (relative to the total silver amount) in the larger AgCu NPs was found to be around 9%, compared to only 5% in that of the smaller AgCu NPs. This indicates that the AgCu alloy content significantly contributes to enhanced antibacterial efficacy, as a higher AgCu content results in the increased release of Ag ions. These findings suggest that the enhanced antimicrobial efficacy of AgCu NPs is primarily attributed to their chemical composition and phase structures, rather than the size of the nanoparticles.

Copper-containing titanium alloys promote the coupling of osteogenesis and angiogenesis by releasing copper ions.

Previous investigations have reported on the ability of copper (Cu)-bearing biomaterials to accelerate vascular formation and bone regeneration. However, few studies have explored the effects of Cu-bearing materials on the interactions between angiogenesis and osteogenesis. Therefore, in this study, we prepared Cu-containing alloys using selective laser melting (SLM) technology and investigated the impact of preosteoblasts seeded on Ti6Al4V-4.5Cu alloy on angiogenesis. Our results indicated that Ti6Al4V-4.5Cu alloys increased the expression of proangiogenic genes and proteins in preosteoblasts, which further stimulated vascular formation in endothelial cells. Besides, we discovered that the biological effects of the Ti6Al4V-4.5Cu alloy were partly attributed to the release of Cu ions. In short, our research demonstrated the ability of Ti6Al4V-4.5Cu alloys to promote the coupling of angiogenesis and osteogenesis by releasing Cu ions.

Integrated MOF-74 Coatings on Magnesium for Corrosion Control, Cytocompatibility, and Antibacterial Properties.

Biodegradable Mg and its alloys can degrade safely in vivo without toxicity. The major bottleneck inhibiting their clinical use is the high corrosion rate, which leads to the loss of mechanical integrity prematurely and bad biocompatibility. One ideal strategy is the modification with anticorrosive and bioactive coatings. Numerous metal-organic framework (MOF) membranes show satisfactory anticorrosion performance and biocompatibility. In this study, MOF-74 membranes are prepared on an NH4TiOF3 (NTiF) layer-modified Mg matrix, fabricating integrated bilayer coatings (MOF-74/NTiF) for corrosion control, cytocompatibility, and antibacterial properties. The inner NTiF layer serves as the primary protection for the Mg matrix and a stable surface for the growth of MOF-74 membranes. The outer MOF-74 membranes further enhance corrosion protection, whose crystals and thicknesses can be adjusted for different protective effects. Owing to superhydrophilic, micro-nanostructural, and nontoxic decomposition products, MOF-74 membranes significantly promote cell adhesion and proliferation, showing excellent cytocompatibility. Utilizing the decomposition of MOF-74 to generate the products of Zn2+ and 2,5-dihydroxyterephthalic acid can effectively inhibit Escherichia coli and Staphylococcus aureus, displaying highly efficient antibacterial properties. The research may shed valuable strategies for MOF-based functional coatings in the applications of biomedicine fields.

Evaluation of toxicity and biocompatibility of a novel Mg-Nd-Gd-Sr alloy in the osteoblastic cell.

BACKGROUND: We investigated the toxicity and biocompatibility of a novel Mg-3Nd-1Gd-0.3Sr-0.2Zn-0.4Zr (abbreviated to Mg-Nd-Gd-Sr) alloy in the osteoblastic cell line MC3T3-E1 as osteoblasts play an important role in bone repair and remodeling. METHODS: We used cytotoxicity tests and apoptosis to investigate the effects of the Mg-Nd-Gd-Sr alloy on osteoblastic cells. Cell bioactivity, cell adhesion, cell proliferation, mineralization, ALP activity, and expression of BMP-2 and OPG by osteoblastic cells were also used to investigate the biocompatibility of Mg-Nd-Gd-Sr alloy. RESULTS: The results showed that the Mg-Nd-Gd-Sr alloy had no obvious cytotoxicity, and did not induce apoptosis to MC3T3-E1 cells. Compared with the control group, the number of adherent cells within 12 h was increased significantly in each experimental group (P < 0.05); the OD value of MC3T3-E1 cells was increased significantly in each experimental group on days 1 and 3 of culture (P < 0.05); the number of mineralized nodules formed in each experimental group was significantly increased (P < 0.05), and ALP activity was significantly increased in each experimental group (P < 0.05). RT-PCR results showed that the mRNA expression of BMP-2 and OPG was significantly higher in each experimental group compared with the control group (P < 0.05). Western blotting showed that the Mg-Nd-Gd-Sr alloy extract significantly increased the protein expression of BMP-2 and OPG compared with the control group (P < 0.05). CONCLUSIONS: Our data indicated that the novel Mg-Nd-Gd-Sr-Zn-Zr alloy had no obvious cytotoxic effects, and did not cause apoptosis to MC3T3-E1 cells; meanwhile it promoted cell adhesion, cell proliferation, mineralization, and ALP activity of osteoblasts. During this process, there was an increase in the expressions of BMP-2 and OPG mRNAs and proteins.

Exploring the functionalization of Ti-6Al-4V alloy with the novel antimicrobial peptide JIChis-2 via plasma polymerization.

This study aimed to characterize the immobilization of the novel JIChis-2 peptide on the Ti-6Al-4V alloy, widely used in the biomedical sector. The antimicrobial activity of JIChis-2 was evaluated in the Gram-negative bacterium E. coli. Its immobilization occurred by inducing the formation of covalent bonds between the N-terminus of the peptides and the surface previously submitted to acrylic acid polymerization via the PECVD technique. Coated and uncoated surfaces were characterized by FTIR, AFM, SEM and EDX. Studies of global and localized corrosion were carried out, seeking to explore the effects triggered by surface treatment in an aggressive environment. Additionally, the ability of the functionalized material to prevent E. coli biofilm formation evidenced that the strategy to immobilize JIChis-2 in the Ti-6Al-4V alloy via PECVD of acrylic acid resulted in the development of a functional material with antibiofilm properties.

Host-device interactions: exposure of lung epithelial cells and fibroblasts to nickel, titanium, or nitinol affect proliferation, reactive oxygen species production, and cellular signaling.

Endoscopic implantation of medical devices for the treatment of lung diseases, including airway stents, unidirectional valves and coils, is readily used to treat central airway disease and emphysema. However, granulation and fibrotic tissue formation impairs treatment effectiveness. To date little is known about the interaction between implanted devices, often made from metals, such as nickel, titanium or nitinol, and cells in the airways. Here, we study the response of lung epithelial cells and fibroblasts to implant device materials. The adhesion and proliferation of bronchial epithelial cells and lung fibroblasts upon exposure to 10 × 3 × 1 mm pieces of nickel, titanium or nitinol is examined using light and scanning electron microscopy. Pro-inflammatory cytokine mRNA expression and release, signaling kinase activity and intracellular free radical production are assessed. Nitinol, and to a lesser extent nickel and titanium, surfaces support the attachment and growth of lung epithelial cells. Nitinol induces a rapid and significant alteration of kinase activity. Cells directly exposed to nickel or titanium produce free radicals, but those exposed to nitinol do not. The response of lung epithelial cells and fibroblasts depends on the metal type to which they are exposed. Nitinol induces cellular surface growth and the induction of kinase activity, while exposure of lung epithelial cells to nickel and titanium induces free radical production, but nitinol does not.

Titanium alloys with varying surface micro-area potential differences have antibacterial abilities and a favorable cellular response.

OBJECTIVES: Surface micro-area potential difference (MAPD) can achieve bacteriostatic performance independent of metal ion dissolution. To study the influence of MAPD on antibacterial properties and the cellular response, Ti-Ag alloys with different surface potentials were designed and prepared by changing the preparation and heat treatment processes. MATERIALS AND METHODS: Ti-Ag alloys (T4, T6, and S) were prepared by vacuum arc smelting, water quenching, and sintering. Cp-Ti was set as a control group in this work. The microstructures and surface potential distributions of the Ti-Ag alloys were analyzed by SEM and energy dispersive spectrometry. Plate counting and live/dead staining methods were used to evaluate the antibacterial properties of the alloys, and the mitochondrial function, ATP levels, and apoptosis were assessed in MC3T3-E1 cells to analyze the cellular response. RESULTS: Due to the formation of the Ti-Ag intermetallic phase in the Ti-Ag alloys, Ti-Ag (T4) without the Ti-Ag phase had the lowest MAPD, Ti-Ag (T6) with a fine Ti2Ag phase had a moderate MAPD, and Ti-Ag (S) with a Ti-Ag intermetallic phase had the highest MAPD. The primary results demonstrated that the Ti-Ag samples with different MAPDs exhibited different bacteriostatic effects, ROS expression levels, and apoptosis-related protein expression levels in cells. The alloy with a high MAPD exhibited a strong antibacterial effect. A moderate MAPD stimulated cellular antioxidant regulation (GSH/GSSG) and downregulated the expression of intracellular ROS. MAPD could also promote the transformation of the inactive mitochondria to biologically active mitochondria by increasing the ΔΨm and reducing apoptosis. CONCLUSION: The results here indicated that moderate MAPD not only had bacteriostatic effects but also promoted mitochondrial function and inhibited cell apoptosis, which provides a new strategy to improve the surface bioactivity of titanium alloys and a new idea for titanium alloy design. CLINICAL RELEVANCE: There are some limitations of the mechanism of MAPD. However, researchers will become increasingly aware of the advantages and disadvantages of MAPD and MAPD might provide an affordable solution of peri-implantitis.

Research progress on antibacterial activity of medical titanium alloy implant materials.

Titanium and its alloys are the preferred materials for medical implants. However, easy infection is a fatal shortcoming of Ti implants. Fortunately, the ongoing development of antibacterial implant materials is a promising solution, and Ti alloys with antibacterial properties hold immense potential for medical applications. In this review, we briefly outline the mechanisms of bacterial colonization and biofilm formation on implants; discuss and classify the major antimicrobials currently in use and development, including inorganic and organic antimicrobials; and describe the important role of antimicrobials in the development of implant materials for clinical applications. Strategies and challenges related to improving the antimicrobial properties of implant materials as well as the prospects of antibacterial Ti alloys in the medical field are also discussed.

Magnesium Alloys in Orthopedics: A Systematic Review on Approaches, Coatings and Strategies to Improve Biocompatibility, Osteogenic Properties and Osteointegration Capabilities.

There is increasing interest in using magnesium (Mg) alloy orthopedic devices because of their mechanical properties and bioresorption potential. Concerns related to their rapid degradation have been issued by developing biodegradable micro- and nanostructured coatings to enhance corrosion resistance and limit the release of hydrogen during degradation. This systematic review based on four databases (PubMed®, Embase, Web of Science™ and ScienceDirect®) aims to present state-of-the-art strategies, approaches and materials used to address the critical factors currently impeding the utilization of Mg alloy devices. Forty studies were selected according to PRISMA guidelines and specific PECO criteria. Risk of bias assessment was conducted using OHAT and SYRCLE tools for in vitro and in vivo studies, respectively. Despite limitations associated with identified bias, the review provides a comprehensive analysis of preclinical in vitro and in vivo studies focused on manufacturing and application of Mg alloys in orthopedics. This attests to the continuous evolution of research related to Mg alloy modifications (e.g., AZ91, LAE442 and WE43) and micro- and nanocoatings (e.g., MAO and MgF2), which are developed to improve the degradation rate required for long-term mechanical resistance to loading and excellent osseointegration with bone tissue, thereby promoting functional bone regeneration. Further research is required to deeply verify the safety and efficacy of Mg alloys.

Effect of Functional Nanoporous TiO2 Film Obtained on Ti6Al4V Implant Alloy to Improve Resistance in Biological Solution for Inflammatory Conditions.

The metallic titanium-based biomaterials are sensitive to corrosion-induced degradation in biological fluids in the presence of inflammatory conditions containing reactive oxygen species (ROS). Excess ROS induces oxidative modification of cellular macromolecules, inhibits protein function, and promotes cell death. In addition, ROS could promote implant degradation by accelerating the corrosive attack of biological fluids. The functional nanoporous titanium oxide film is obtained on titanium alloy to study the effect on implant reactivity in biological fluid with reactive oxygen species such as hydrogen peroxide, which are present in inflammations. The TiO2 nanoporous film is obtained by electrochemical oxidation at high potential. The untreated Ti6Al4V implant alloy and nanoporous titanium oxide film are comparatively evaluated for corrosion resistance in biological solution by Hank's and Hank's doped with hydrogen peroxide by electrochemical methods. The results showed that the presence of the anodic layer significantly improved the resistance of the titanium alloy to corrosion-induced degradation in biological solutions under inflammatory conditions.

In Vitro and In Vivo Studies of Antibacterial Coatings on Titanium Alloy Implants for Veterinary Application.

The aim of this work was the evaluation of biological properties of hybrid coatings modified with Ag, Cu, and Zn nanoparticles (NPs) applied on TPLO medical implants by the sol-gel process. The implant coatings enriched with various concentrations of metallic NPs were investigated in the in vitro bactericidal efficacy tests against Gram+ and Gram- bacteria and pathogenic yeast. Next, the designed materials were tested on human osteosarcoma cell lines. The cells adhesion, proliferation, viability, and differentiation were investigated. The cell growth wasevaluated using SEM, and the metallic ion release was measured. The results revealed that the NPs concentration in the hybrid layers decreased with the incubation time. In the last stage, the implants were tested in vivo on six canine patients. Three months after the operation, the radiological evaluation of the performed anastomosis was carried out as well as the histopathological evaluation of tissue regeneration. The strongest bactericidal efficacy was observed for the layers containing AgNPs. Along with an increased concentration of metallic additives, a growing toxic effect was clearly observed. The most pronounced toxic effect was especially evident with the AgNPs concentration exceeding 1 mol %. In all the operated patients, no deviations were found during the follow-up examinations in the postoperative period. The low dose of AgNPs in the hybrid layer facilitated the tissue healing process. It was proven that silver nanoparticles may accelerate the bone healing process. The correct tissue reparation was observed.

In Vivo Degradation Behavior of Magnesium Alloy for Bone Implants with Improving Biological Activity, Mechanical Properties, and Corrosion Resistance.

This study aimed to establish a surface modification technology for ZK60 magnesium alloy implants that can degrade uniformly over time and promote bone healing. It proposes a special micro-arc oxidation (MAO) treatment on ZK60 alloy that enables the composite electrolytes to create a coating with better corrosion resistance and solve the problems of uneven and excessive degradation. A magnesium alloy bone screw made in this way was able to promote the bone healing reaction after implantation in rabbits. Additionally, it was found that the MAO-treated samples could be sustained in simulated body-fluid solution, exhibiting excellent corrosion resistance and electrochemical stability. The Ca ions deposited in the MAO coating were not cytotoxic and were beneficial in enhancing bone healing after implantation.

Effects of Ageing in Disinfectant Solution on the Corrosion Resistance and Antimicrobial Behavior of Copper Alloys.

This work studies two copper-based alloys as potential antimicrobial weapons for sectors where surface hygiene is essential. Effects of different alloying elements addition at the same Cu content (92.5% by weight) on the corrosion resistance and the antibacterial performance of two copper alloys were studied in an aerated disinfectant solution (0.25% v/v Aniosurf Premium (D)) by electrochemical corrosion, X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectroscopy (ToF-SIMS) and antibacterial tests. Results showed that the nature of the alloying elements had a clear influence on the corrosion resistance and antibacterial performance. Electrochemical impedance results and surface analyses demonstrate the presence of organic compounds bound on the substrate and that a film covers part of the total active surface and may act as a protective barrier by preventing the interaction between metal and solution, decreasing the antimicrobial performance of copper-based materials. Low zinc and silicon contents in copper alloys allows for better aging behavior in D solution while maintaining good antibacterial performance. The XPS and ToF-SIMS results indicated that artificial aging in disinfectant enhanced Cu enrichment in the organic film formed, which could effectively stimulate the release of Cu ions from the surface.

Graphene Coated Ti-6Al-4V Exhibits Antibacterial and Antifungal Properties Against Oral Pathogens.

PURPOSE: This study aimed to explore the antimicrobial properties of graphene coated Ti-6Al-4V to oral pathogens. MATERIALS AND METHODS: Graphene directly synthesized on Ti-6Al-4V alloy was characterized by scanning electron microscopy (SEM) and Raman spectroscopy. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, live/dead fluorescent staining and SEM were used to analyze the antimicrobial properties of graphene coated Ti-6Al-4V alloy to Porphyromonas gingivalis (P. gingivalis), Fusobacterium nucleatum (F. nucleatum), and Candida albicans (C. albicans). Reactive oxygen species (ROS) generation was monitored to reveal the antimicrobial mechanism. RESULTS: Graphene coated Ti-6Al-4V alloy caused a significant reduction in the presence of both bacterial and fungal pathogens as compared to uncoated Ti-6Al-4V alloy. P. gingivalis, F. nucleatum, and C. albicans on graphene coated Ti-6Al-4V alloy were less active than on uncoated Ti-6Al-4V alloy, and tended to become shrunk and deformed. Meanwhile, graphene coated Ti-6Al-4V alloy induced more generation of ROS in the pathogens than uncoated Ti-6Al-4V alloy. CONCLUSIONS: Graphene coated Ti-6Al-4V alloy exhibited antimicrobial properties against oral pathogens, the induction of oxidative stress might be involved in its antimicrobial mechanisms.

Comparison of the Effects of 3D Printing Bioactive Porous Titanium Alloy Scaffolds and Nano-biology for Direct Treatment of Bone Defects.

This study was to compare the effects of three-dimensional (3D) printed bioactive porous titanium alloy scaffolds (3DP-BPTAS) and rhBMP-2/PLA-loaded sustained-release nanospheres (SRNs) in the treatment of bone defects. In this study, the bioactive porous titanium alloy scaffolds (BPTAS) with different pore sizes were prepared by selective laser melting (SLM) technology. The rhBMP-2/PLA SRNs were prepared by the double emulsion solvent volatilization method. The morphology of the two nanomaterials was observed under a scanning electron microscope (SEM). The encapsulation rate (ER), drug loading (DL), and in vitro release rate of the SRNs were detected by enzyme-linked immunosorbent assay (ELISA); and the effects of different particle sizes of BPTAS and SRNs on the proliferation of BMSCs were measured using the Methyl Thiazolyl Tetrazolium (MTT) method. 42 healthy male rabbits were selected and rolled into a control group (no treatment), a model group (the femoral condyle defect model), an A800 group (model + 800 µm of BPTAS), and an A1000 group (model + 1000 µm of BPTAS), an A1200 group (model + 1200 µm of BPTAS), an A1500 group (model + 1500 µm of BPTAS), and an SNR group (model + rhBMP-2/PLA SRNs). There were 6 rabbits in each group, and they were sacrificed 4, 8, and 12 weeks after the surgery. They were performed with general observation, X-ray photography, and histological and biomechanical examinations. According to the Lane-Sandhu bone defect repair tissue X-ray and histological scoring standard, the effect of bone defect repair was evaluated. It was found that the actual pore structure of the scaffold prepared by the SLM process was consistent with the theoretical design. The observation under TEM showed that rhBMP-2/PLA SRNs were approximately round, with an average particle size of 835 nm, and its encapsulation efficiency and drug loading rate were 89.02 ± 5.14% and 0.033 ± 0.004%, respectively. The rhBMP-2/PLA SRNs and BPTAS had no statistically obvious increase in the number of cells after cell treatment compared with the control group (P> 0.05). At 12 weeks postoperatively, the stent bone tissue growing distance (SBTGD) in the SRN group was longer than that in the A1000 group (P< 0.01), and that in the A1000 group was better in contrast to the A800, A1200, and A1500 groups (P< 0.01). The Lane-Sandhu X-ray score of the SRN group was better than other groups (P< 0.05). It suggested that 3DP-BPTAS and rhBMP-2/PLA SRNs could repair the bone defects, and rhBMP-2/PLA SRNs were more conducive to the formation of new bone tissue.