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1.
Langmuir ; 40(32): 16791-16803, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39086155

ABSTRACT

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.


Subject(s)
Alloys , Anti-Bacterial Agents , Escherichia coli , Lasers , Surface Properties , Titanium , Titanium/chemistry , Titanium/pharmacology , Alloys/chemistry , Alloys/pharmacology , Escherichia coli/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
2.
Langmuir ; 40(33): 17301-17310, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39106975

ABSTRACT

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.


Subject(s)
Alloys , Macrophages , Surface Properties , Titanium , Titanium/chemistry , Alloys/chemistry , Alloys/pharmacology , Adsorption , Humans , Macrophages/drug effects , Macrophages/immunology , Cell Differentiation/drug effects , Osteoblasts/drug effects , Osteoblasts/cytology
3.
ACS Appl Mater Interfaces ; 16(34): 44590-44604, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39153190

ABSTRACT

Titanium and titanium alloys have the advantages of a low density and a close elastic modulus to natural bone, which can reduce the stress-shielding effect and become one of the first choices for human hard tissue replacement and repair. However, implant site infection is still one of the main reasons for implantation failure. In this paper, 2.5 wt % Ag element was added to Ti-15Mo to obtain a low modulus, and a surface anodization was applied to improve the surface biocompatibility. The elastic modulus, micromorphology, surface elemental valence, corrosion resistance, antimicrobial properties, and cytocompatibility were investigated by mechanical tests, scanning electron microscopy, X-ray photoelectron spectroscopy, electrochemical tests, inductively coupled plasma spectroscopy, plate counting method, and cellular tests. The experimental results showed that the anodized Ti-15Mo-2.5Ag sample exhibited an elastic modulus of 79 GPa, a strong corrosion resistance, a strong antimicrobial ability of ≥99.99%, and good biocompatibility. It was demonstrated that the formation of Ag2O on the surface and Ag ion release improved the antimicrobial properties and that the structural synergism of silver ions with micro- and nanostructures played an important role in promoting the early spreading of cells and improving the cytocompatibility.


Subject(s)
Silver , Titanium , Titanium/chemistry , Titanium/pharmacology , Silver/chemistry , Silver/pharmacology , Nanostructures/chemistry , Molybdenum/chemistry , Molybdenum/pharmacology , Alloys/chemistry , Alloys/pharmacology , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Materials Testing , Animals , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Surface Properties , Mice , Corrosion
4.
Chem Commun (Camb) ; 60(60): 7729-7732, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38973292

ABSTRACT

Implant infections are a major challenge for the healthcare system. Biofilm formation and increasing antibiotic resistance of common bacteria cause implant infections, leading to an urgent need for alternative antibacterial agents. In this study, the antibiofilm behaviour of a coating consisting of a silver (Ag)/gold (Au) nanoalloy is investigated. This alloy is crucial to reduce uncontrolled potentially toxic Ag+ ion release. In neutral pH environments this release is minimal, but the Ag+ ion release increases in acidic microenvironments caused by bacterial biofilms. We perform a detailed physicochemical characterization of the nanoalloys and compare their Ag+ ion release with that of pure Ag nanoparticles. Despite a lower released Ag+ ion concentration at pH 7.4, the antibiofilm activity against Escherichia coli (a bacterium known to produce acidic pH environments) is comparable to a pure nanosilver sample with a similar Ag-content. Finally, biocompatibility studies with mouse pre-osteoblasts reveal a decreased cytotoxicity for the alloy coatings and nanoparticles.


Subject(s)
Alloys , Anti-Bacterial Agents , Biofilms , Escherichia coli , Gold , Metal Nanoparticles , Silver , Silver/chemistry , Silver/pharmacology , Biofilms/drug effects , Gold/chemistry , Gold/pharmacology , Hydrogen-Ion Concentration , Mice , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Escherichia coli/drug effects , Alloys/chemistry , Alloys/pharmacology , Metal Nanoparticles/chemistry , Microbial Sensitivity Tests , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Ions/chemistry , Ions/pharmacology , Prostheses and Implants , Cell Survival/drug effects
5.
Molecules ; 29(13)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38998976

ABSTRACT

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.


Subject(s)
Alloys , Copper , Metal Nanoparticles , Microbial Sensitivity Tests , Particle Size , Silver , Copper/chemistry , Metal Nanoparticles/chemistry , Alloys/chemistry , Alloys/pharmacology , Silver/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
6.
Int J Nanomedicine ; 19: 6427-6447, 2024.
Article in English | MEDLINE | ID: mdl-38952675

ABSTRACT

Background: Implants are widely used in the field of orthopedics and dental sciences. Titanium (TI) and its alloys have become the most widely used implant materials, but implant-associated infection remains a common and serious complication after implant surgery. In addition, titanium exhibits biological inertness, which prevents implants and bone tissue from binding strongly and may cause implants to loosen and fall out. Therefore, preventing implant infection and improving their bone induction ability are important goals. Purpose: To study the antibacterial activity and bone induction ability of titanium-copper alloy implants coated with nanosilver/poly (lactic-co-glycolic acid) (NSPTICU) and provide a new approach for inhibiting implant-associated infection and promoting bone integration. Methods: We first examined the in vitro osteogenic ability of NSPTICU implants by studying the proliferation and differentiation of MC3T3-E1 cells. Furthermore, the ability of NSPTICU implants to induce osteogenic activity in SD rats was studied by micro-computed tomography (micro-CT), hematoxylin-eosin (HE) staining, masson staining, immunohistochemistry and van gieson (VG) staining. The antibacterial activity of NSPTICU in vitro was studied with gram-positive Staphylococcus aureus (Sa) and gram-negative Escherichia coli (E. coli) bacteria. Sa was used as the test bacterium, and the antibacterial ability of NSPTICU implanted in rats was studied by gross view specimen collection, bacterial colony counting, HE staining and Giemsa staining. Results: Alizarin red staining, alkaline phosphatase (ALP) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis showed that NSPTICU promoted the osteogenic differentiation of MC3T3-E1 cells. The in vitro antimicrobial results showed that the NSPTICU implants exhibited better antibacterial properties. Animal experiments showed that NSPTICU can inhibit inflammation and promote the repair of bone defects. Conclusion: NSPTICU has excellent antibacterial and bone induction ability, and has broad application prospects in the treatment of bone defects related to orthopedics and dental sciences.


Subject(s)
Anti-Bacterial Agents , Coated Materials, Biocompatible , Escherichia coli , Osteogenesis , Polylactic Acid-Polyglycolic Acid Copolymer , Rats, Sprague-Dawley , Staphylococcus aureus , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Osteogenesis/drug effects , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Mice , Staphylococcus aureus/drug effects , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Escherichia coli/drug effects , Cell Differentiation/drug effects , Prostheses and Implants , Alloys/pharmacology , Alloys/chemistry , Rats , Titanium/chemistry , Titanium/pharmacology , Silver/chemistry , Silver/pharmacology , Cell Proliferation/drug effects , Copper/chemistry , Copper/pharmacology , Male , X-Ray Microtomography , Cell Line , Metal Nanoparticles/chemistry
7.
Int J Biol Macromol ; 277(Pt 1): 133806, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38996886

ABSTRACT

Bone defects, resulting from trauma, inflammation, tumors, and various other factors, affect both health and quality of life. Although autologous bone transplantation is the gold-standard treatment for bone defects, it has disadvantages such as donor site limitations, prolonged surgical durations, and potential complications, necessitating the development of alternative bone tissue engineering materials. In this study, we used 3D printing technology to fabricate porous titanium implants characterized by superior biocompatibility and mechanical properties. Sodium alginate (SA) and strontium ions (Sr2+) were integrated into mineralized collagen matrices (MCs) to develop strontium-functionalized alginate-mineralized collagen hydrogels (SAMs) with high mechanical strength and sustained metal ion release ability. SAMs were seamlessly incorporated into the porous structures of 3D-printed titanium scaffolds, establishing a novel organic-inorganic bioactive interface. This composite system exhibited high biocompatibility in vitro and increased the expression of genes important for osteogenic differentiation and angiogenesis. In a rabbit model of femoral defect, the titanium implants effectively promoted bone and vascular regeneration on their surface, highlighting their potential in facilitating bone-implant integration.


Subject(s)
Alloys , Collagen , Hydrogels , Osseointegration , Osteogenesis , Printing, Three-Dimensional , Tissue Scaffolds , Titanium , Titanium/chemistry , Animals , Osteogenesis/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Tissue Scaffolds/chemistry , Rabbits , Osseointegration/drug effects , Collagen/chemistry , Collagen/pharmacology , Porosity , Alloys/chemistry , Alloys/pharmacology , Neovascularization, Physiologic/drug effects , Strontium/chemistry , Strontium/pharmacology , Tissue Engineering/methods , Alginates/chemistry , Alginates/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
8.
Int J Biol Macromol ; 276(Pt 2): 134050, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39038567

ABSTRACT

Although titanium alloy is the most widely used endoplant material in orthopedics, the material is bioinert and good bone integration is difficult to achieve. Zoledronic acid (ZOL) has been shown to locally inhibit osteoclast formation and prevent osteoporosis, but excessive concentrations of ZOL exert an inhibitory effect on osteoblasts; therefore, stable and controlled local release of ZOL may reshape bone balance and promote bone regeneration. To promote the adhesion of osteoblasts to many polar groups, researchers have applied gelatine methacryloyl (Gelma) combined with polyacrylamide hydrogel (PAAM), which significantly increased the hydrogen bonding force between the samples and improved the stability of the coating and drug release. A series of experiments demonstrated that the Gelma/PAAM-ZOL bioactive coating on the surface of the titanium alloy was successfully prepared. The coating can induce osteoclast apoptosis, promote osteoblast proliferation and differentiation, achieve dual regulation of bone regeneration, successfully disrupt the balance of bone remodelling and promote bone tissue regeneration. Additionally, the coating improves the metal biological inertness on the surface of titanium alloys and improves the bone integration of the scaffold, offering a new strategy for bone tissue engineering to promote bone technology.


Subject(s)
Alloys , Hydrogels , Osteoblasts , Osteogenesis , Printing, Three-Dimensional , Tissue Scaffolds , Titanium , Zoledronic Acid , Titanium/chemistry , Hydrogels/chemistry , Alloys/chemistry , Alloys/pharmacology , Osteogenesis/drug effects , Tissue Scaffolds/chemistry , Animals , Osteoblasts/drug effects , Osteoblasts/cytology , Zoledronic Acid/pharmacology , Zoledronic Acid/chemistry , Porosity , Cell Proliferation/drug effects , Acrylic Resins/chemistry , Cell Differentiation/drug effects , Gelatin/chemistry , Bone Regeneration/drug effects , Tissue Engineering/methods , Humans , Osteoclasts/drug effects
9.
ACS Appl Bio Mater ; 7(8): 5728-5739, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39037897

ABSTRACT

Implants made from titanium are used as prostheses because of their biocompatibility and their mechanical properties close to those of human bone. However, the risk of bacterial infection is always a major concern during surgery, and the development of biofilm can make these infections difficult to treat. A promising strategy to mitigate against bacterial infections is the use of antifouling and antimicrobial coatings, where bioresorbable polymers can play an important role due to their controlled degradability and sustained drug release, as well as excellent biocompatibility. In the present study, poly(d,l-lactide) (PDLLA) and poly[d,l-lactide-co-methyl ether poly(ethylene glycol)] (PDLLA-PEG) were studied, varying the PEG content (20-40% w/w) to analyze the effectiveness of PEG as an antifouling molecule. In addition, silver sulfadiazine (AgSD) was used as an additional antimicrobial agent with a concentration ≤5% w/w and incorporated into the PEGylated polymers to create a polymer with both antifouling and antimicrobial properties. Polymers synthesized were applied using spin coating to obtain homogeneous coatings to protect samples made from titanium/aluminum/vanadium (Ti6Al4V). The polymer coatings had a smoothing effect in comparison to that of the uncoated material, decreasing the contact area available for bacterial colonization. It was also noted that PEG addition into the polymeric chain developed amphiphilic materials with a decrease in contact angle from the most hydrophobic (Ti6Al4V) to the most hydrophilic PDLLA-PEG (60/40), highlighting the increase in water uptake contributing to the hydration layer formation, which confers the antifouling effect on the coating. This study demonstrated that the addition of PEG above 20% w/w and AgSD above 1% w/v into the formulation was able to decrease bacterial adherence against clinically relevant biofilm former strains Staphylococcus aureus and Pseudomonas aeruginosa.


Subject(s)
Alloys , Anti-Bacterial Agents , Biofilms , Coated Materials, Biocompatible , Materials Testing , Polyesters , Staphylococcus aureus , Titanium , Biofilms/drug effects , Titanium/chemistry , Titanium/pharmacology , Alloys/chemistry , Alloys/pharmacology , Polyesters/chemistry , Polyesters/pharmacology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Humans , Particle Size , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Surface Properties , Prostheses and Implants
10.
ACS Biomater Sci Eng ; 10(8): 4927-4937, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-38967561

ABSTRACT

Nickel-titanium alloy stents are widely used in the interventional treatment of various malignant tumors, and it is important to develop nickel-titanium alloy stents with selective cancer-inhibiting and antibacterial functions to avoid malignant obstruction caused by tumor invasion and bacterial colonization. In this work, an acid-responsive layered double hydroxide (LDH) film was constructed on the surface of a nickel-titanium alloy by hydrothermal treatment. The release of nickel ions from the film in the acidic tumor microenvironment induces an intracellular oxidative stress response that leads to cell death. In addition, the specific surface area of LDH nanosheets could be further regulated by heat treatment to modulate the release of nickel ions in the acidic microenvironment, allowing the antitumor effect to be further enhanced. This acid-responsive LDH film also shows a good antibacterial effect against S. aureus and E. coli. Besides, the LDH film prepared without the introduction of additional elements maintains low toxicity to normal cells in a normal physiological environment. This work offers some guidance for the design of a practical nickel-titanium alloy stent for the interventional treatment of tumors.


Subject(s)
Anti-Bacterial Agents , Hydroxides , Nickel , Tumor Microenvironment , Hydroxides/chemistry , Hydroxides/pharmacology , Tumor Microenvironment/drug effects , Nickel/chemistry , Nickel/pharmacology , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Alloys/chemistry , Alloys/pharmacology , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Titanium/chemistry , Titanium/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Hydrogen-Ion Concentration
11.
ACS Appl Bio Mater ; 7(6): 3900-3914, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38840339

ABSTRACT

The poor clinical performance of titanium and its alloy implants is mainly attributed to their lack of antibacterial ability and poor osseointegration. The key and challenge lie in how to enhance their osteoinductivity while imparting antibacterial capability. In this study, a titanium oxide metasurface with light-responsive behavior was constructed on the surface of titanium alloy using an alkaline-acid bidirectional hydrothermal method. The effects of the acid type, acid concentration, hydrothermal time, hydrothermal temperature, and subsequent heat treatments on the optical behavior of the metasurface were systematically investigated with a focus on exploring the influence of the metasurface and photodynamic reaction on the osteogenic activity of osteoblasts. Results show that the type of acid and heat treatment significantly affect the light absorption of the titanium alloy surface, with HCl and post-heat-treatment favoring redshift in the light absorption. Under 808 nm near-infrared (NIR) irradiation for 10 min, in vitro antibacterial experiments demonstrate that the antibacterial rate of the metasurface titanium alloy against Staphylococcus aureus and Escherichia coli were 96.87% and 99.27%, respectively. In vitro cell experiments demonstrate that the nanostructure facilitates cell adhesion, proliferation, differentiation, and expression of osteogenic-related genes. Surprisingly, the nanostructure promoted the expression of relevant osteogenic genes of MC3T3-E1 under 808 nm NIR irradiation. This study provides a method for the surface modification of titanium alloy implants.


Subject(s)
Alloys , Anti-Bacterial Agents , Biocompatible Materials , Escherichia coli , Infrared Rays , Materials Testing , Nanostructures , Staphylococcus aureus , Surface Properties , Titanium , Titanium/chemistry , Titanium/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Staphylococcus aureus/drug effects , Alloys/chemistry , Alloys/pharmacology , Escherichia coli/drug effects , Nanostructures/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Microbial Sensitivity Tests , Particle Size , Animals , Mice , Osteogenesis/drug effects , Osteoblasts/drug effects , Osteoblasts/cytology , Cell Proliferation/drug effects , Osseointegration/drug effects
12.
J Mech Behav Biomed Mater ; 157: 106605, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38852242

ABSTRACT

Peri-implantitis and insufficient osseointegration are the principal challenges faced by dental implants at present. In order to fabricate dual-function dental implant materials possessing both antibacterial and osteogenic capabilities, this study incorporates the antimicrobial element Cu into the Ti40Nb alloy, developing a novel Ti40Nb-xCu alloy with antibacterial properties. Among them, Ti40Nb3Cu has the best overall performance. Compared to Ti40Nb, the tensile strength increased by 27.97%, reaching 613 MPa. Although the elongation rate has decreased from 23% to 13.5%, the antibacterial rates against S. aureus and P. gingivalis both exceed 85%. Furthermore, the surface of Ti40Nb-xCu alloy was then treated with micro-arc oxidation to enhance its bioactivity, thereby accelerating osseointegration. The results indicated that the MAO treatment retains the antibacterial properties of the Ti40Nb3Cu alloy while significantly promoting bone formation through its introduced porous coating, thus heralding it as a propitious candidate material for dental implant applications.


Subject(s)
Alloys , Anti-Bacterial Agents , Dental Implants , Materials Testing , Oxidation-Reduction , Staphylococcus aureus , Surface Properties , Titanium , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Alloys/chemistry , Alloys/pharmacology , Staphylococcus aureus/drug effects , Titanium/chemistry , Titanium/pharmacology , Porphyromonas gingivalis/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Animals , Copper/chemistry , Copper/pharmacology , Mice , Niobium/chemistry
13.
ACS Appl Mater Interfaces ; 16(25): 31983-31996, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38865688

ABSTRACT

Effective osteointegration is of great importance for pedicle screws in spinal fusion surgeries. However, the lack of osteoinductive activity of current screws diminishes their feasibility for osteointegration and fixation, making screw loosening a common complication worldwide. In this study, Ti-6Al-4V pedicle screws with full through-hole design were fabricated via selective laser melting (SLM) 3D printing and then deposited with porous oxide coatings by microarc oxidation (MAO). The porous surface morphology of the oxide coating and the release of bioactive ions could effectively support cell adhesion, migration, vascularization, and osteogenesis in vitro. Furthermore, an in vivo goat model demonstrated the efficacy of modified screws in improving bone maturation and osseointegration, thus providing a promising method for feasible orthopedic internal fixation.


Subject(s)
Ceramics , Goats , Osseointegration , Oxidation-Reduction , Pedicle Screws , Printing, Three-Dimensional , Titanium , Animals , Osseointegration/drug effects , Titanium/chemistry , Titanium/pharmacology , Ceramics/chemistry , Ceramics/pharmacology , Alloys/chemistry , Alloys/pharmacology , Osteogenesis/drug effects , Humans , Porosity , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Cell Adhesion/drug effects
14.
ACS Appl Mater Interfaces ; 16(25): 32566-32577, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38867413

ABSTRACT

In this work, the hydroxyapatite (HA) microspheres are utilized as carriers for 8-hydroxyquinoline (8-HQ) inhibitors with a sodium alginate-silver nitrate layer (Ag-SA) added to confer chloride-responsive properties. These 8-HQ@Ag-SA-HA microspheres are subsequently integrated into poly(lactic acid) (PLA) coatings to produce biocompatible coatings. The resulting 8-HQ@Ag-SA-HA microsphere exhibits a spherical structure with a diameter of 3.16 µm. Thermogravimetric analysis indicates that the encapsulated 8-HQ inhibitors are approximately 11.83 wt %. Furthermore, the incorporation of these microspheres fills the micropores within the PLA coating, leading to a denser coating surface, enhanced wettability (contact angle value = 88°), and improved adhesion strength, thereby reinforcing the physical barrier effect. Corrosion tests reveal that the coatings exhibit increased resistance to corrosion in simulated body fluid (SBF) solutions. The released 8-HQ inhibitors in response to chloride ions form a protective layer of Mg(HQ)2, providing the coatings with self-healing properties and ensuring their durability in the SBF environment. Additionally, the cell test demonstrates a significant presence of MG-63 cells, accompanied by a low hemolysis rate of 3.81%, confirming the exceptional biocompatibility of the coatings. These findings offer valuable insights into the development of stimuli-responsive biocompatible coatings for effectively protecting Mg alloys.


Subject(s)
Alloys , Chlorides , Coated Materials, Biocompatible , Magnesium , Alloys/chemistry , Alloys/pharmacology , Humans , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Magnesium/chemistry , Magnesium/pharmacology , Chlorides/chemistry , Durapatite/chemistry , Durapatite/pharmacology , Corrosion , Microspheres , Alginates/chemistry , Polyesters/chemistry
15.
ACS Biomater Sci Eng ; 10(7): 4452-4462, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38875708

ABSTRACT

Mg-based biodegradable metallic implants are gaining increased attraction for applications in orthopedics and dentistry. However, their current applications are hampered by their high rate of corrosion, degradation, and rapid release of ions and gas bubbles into the physiological medium. The aim of the present study is to investigate the osteogenic and angiogenic potential of coated Mg-based implants in a sheep cranial defect model. Although their osteogenic potential was studied to some extent, their potential to regenerate vascularized bone formation was not studied in detail. We have studied the potential of magnesium-calcium (MgCa)-based alloys modified with zinc (Zn)- or gallium (Ga)-doped calcium phosphate (CaP) coatings as a strategy to control their degradation rate while enhancing bone regeneration capacity. MgCa and its implants with CaP coatings (MgCa/CaP) as undoped or as doped with Zn or Ga (MgCa/CaP + Zn and MgCa/CaP + Ga, respectively) were implanted in bone defects created in the sheep cranium. MgCa implants degraded faster than the others at 4 weeks postop and the weight loss was ca. 50%, while it was ca. 15% for MgCa/CaP and <10% in the presence of Zn and Ga with CaP coating. Scanning electron microscopy (SEM) analysis of the implant surfaces also revealed that the MgCa implants had the largest degree of structural breakdown of all the groups. Radiological evaluation revealed that surface modification with CaP to the MgCa implants induced better bone regeneration within the defects as well as the enhancement of bone-implant surface integration. Bone volume (%) within the defect was ca. 25% in the case of MgCa/CaP + Ga, while it was around 15% for undoped MgCa group upon micro-CT evaluation. This >1.5-fold increase in bone regeneration for MgCa/CaP + Ga implant was also observed in the histopathological examination of the H&E- and Masson's trichrome-stained sections. Immunohistochemical analysis of the bone regeneration (antiosteopontin) and neovascularization (anti-CD31) at the defect sites revealed >2-fold increase in the expression of the markers in both Ga- and Zn-doped, CaP-coated implants. Zn-doped implants further presented low inflammatory reaction, notable bone regeneration, and neovascularization among all the implant groups. These findings indicated that Ga- and Zn-doped CaP coating is an important strategy to control the degradation rate as well as to achieve enhanced bone regeneration capacity of the implants made of Mg-based alloys.


Subject(s)
Alloys , Calcium Phosphates , Coated Materials, Biocompatible , Gallium , Magnesium , Osteogenesis , Skull , Zinc , Animals , Zinc/chemistry , Zinc/pharmacology , Sheep , Skull/drug effects , Skull/pathology , Skull/injuries , Osteogenesis/drug effects , Magnesium/pharmacology , Gallium/chemistry , Gallium/pharmacology , Alloys/chemistry , Alloys/pharmacology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Bone Regeneration/drug effects , Calcium/metabolism , Absorbable Implants
16.
J Mater Chem B ; 12(32): 7814-7825, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-38895823

ABSTRACT

In recent decades, orthopedic implants have been widely used as materials to replace human bone tissue functions. Among these, metal implants play a crucial role. Metals with better chemical stability, such as stainless steel, titanium alloys, and cobalt-chromium-molybdenum (CoCrMo) alloy, are commonly used for long-term applications. However, good chemical stability can result in poor tissue integration between the tissue and the implant, leading to potential inflammation risks. This study creates hydrogenated CoCrMo (H-CoCrMo) surfaces, which have shown promise as anti-inflammatory orthopedic implants. Using the electrochemical cathodic hydrogen-charging method, the surface of the CoCrMo alloy was hydrogenated, resulting in improved biocompatibility, reduced free radicals, and an anti-inflammatory response. Hydrogen diffusion to a depth of approximately 106 ± 27 nm on the surface facilitated these effects. This hydrogen-rich surface demonstrated a reduction of 85.2% in free radicals, enhanced hydrophilicity as evidenced by a decrease in a contact angle from 83.5 ± 1.9° to 52.4 ± 2.2°, and an increase of 11.4% in hydroxyapatite deposition surface coverage. The cell study results revealed a suppression of osteosarcoma cell activity to 50.8 ± 2.9%. Finally, the in vivo test suggested the promotion of new bone formation and a reduced inflammatory response. These findings suggest that electrochemical hydrogen charging can effectively modify CoCrMo surfaces, offering a potential solution for improving orthopedic implant outcomes through anti-inflammatory mechanisms.


Subject(s)
Biocompatible Materials , Hydrogen , Inflammation , Vitallium , Inflammation/drug therapy , Inflammation/chemically induced , Humans , Hydrogen/chemistry , Vitallium/chemistry , Vitallium/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Surface Properties , Prostheses and Implants , Animals , Alloys/chemistry , Alloys/pharmacology , Cobalt/chemistry , Materials Testing , Mice , Particle Size
17.
Acta Biomater ; 181: 469-482, 2024 06.
Article in English | MEDLINE | ID: mdl-38723926

ABSTRACT

Medium-entropy alloys (MEAs) typically exhibit outstanding mechanical properties, but their high Young's modulus results in restricted clinical applications. Mismatched Young's modulus between implant materials and human bones can lead to "stress shielding" effects, leading to implant failure. In contrast, ß-Ti alloys demonstrate a lower Young's modulus compared to MEAs, albeit with lower strength. In the present study, based on the bimodal grain size distribution (BGSD) strategy, a series of high-performance TiZrNbTa/Ti composites are obtained by combining TiZrNbTa MEA powders with nano-scale grain sizes and commercially pure Ti (CP-Ti) powders with micro-scale grain sizes. Concurrently, Zr, Nb, and Ta that are ß-Ti stabilizer elements diffuse into Ti, inducing an isomorphous transformation in Ti from the high Young's modulus α-Ti phase to the low Young's modulus ß-Ti phase at room temperature, optimizing the mechanical biocompatibility. The TiZrNbTa/ß-Ti composite demonstrates a yield strength of 1490 ± 83 MPa, ductility of 20.7 % ± 2.9 %, and Young's modulus of 87.6 ± 1.6 GPa. Notably, the yield strength of the TiZrNbTa/ß-Ti composite surpasses that of sintered CP-Ti by 2.6-fold, and its ductility outperforms TiZrNbTa MEA by 2.3-fold. The Young's modulus of the TiZrNbTa/ß-Ti composite is reduced by 28 % and 36 % compared to sintered CP-Ti and TiZrNbTa MEA, respectively. Additionally, it demonstrates superior biocompatibility compared to CP-Ti plate, sintered CP-Ti, and TiZrNbTa MEA. With a good combination of mechanical properties and biocompatibility, the TiZrNbTa/ß-Ti composite exhibits significant potential for clinical applications as metallic biomaterials. STATEMENT OF SIGNIFICANCE: This work combines TiZrNbTa MEA with nano-grains and commercially pure Ti with micro-grains to fabricate a TiZrNbTa/ß-Ti composite with bimodal grain-size, which achieves a yield strength of 1490 ± 83 MPa and a ductility of 20.7 % ± 2.9 %. Adhering to the ISO 10993-5 standard, the TiZrNbTa/ß-Ti composite qualifies as a non-cytotoxic material, achieving a Class 0 cytotoxicity rating and demonstrating outstanding biocompatibility akin to commercially pure Ti. Drawing on element diffusion, Zr, Nb, and Ta serve not only as solvent atoms to achieve solid-solution strengthening but also as stabilizers for the transformation of the ß-Ti crystal structure. This work offers a novel avenue for designing advanced biomedical Ti alloys with elevated strength and plasticity alongside a reduced Young's modulus.


Subject(s)
Alloys , Biocompatible Materials , Materials Testing , Titanium , Titanium/chemistry , Titanium/pharmacology , Alloys/chemistry , Alloys/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Animals , Elastic Modulus , Humans , Niobium/chemistry , Niobium/pharmacology , Zirconium/chemistry , Zirconium/pharmacology , Phase Transition , Mice
18.
Acta Biomater ; 182: 139-155, 2024 07 01.
Article in English | MEDLINE | ID: mdl-38750914

ABSTRACT

Additively manufactured (AM) biodegradable zinc (Zn) alloys have recently emerged as promising porous bone-substituting materials, due to their moderate degradation rates, good biocompatibility, geometrically ordered microarchitectures, and bone-mimicking mechanical properties. While AM Zn alloy porous scaffolds mimicking the mechanical properties of trabecular bone have been previously reported, mimicking the mechanical properties of cortical bone remains a formidable challenge. To overcome this challenge, we developed the AM Zn-3Mg alloy. We used laser powder bed fusion to process Zn-3Mg and compared it with pure Zn. The AM Zn-3Mg alloy exhibited significantly refined grains and a unique microstructure with interlaced α-Zn/Mg2Zn11 phases. The compressive properties of the solid Zn-3Mg specimens greatly exceeded their tensile properties, with a compressive yield strength of up to 601 MPa and an ultimate strain of >60 %. We then designed and fabricated functionally graded porous structures with a solid core and achieved cortical bone-mimicking mechanical properties, including a compressive yield strength of >120 MPa and an elastic modulus of ≈20 GPa. The biodegradation rates of the Zn-3Mg specimens were lower than those of pure Zn and could be adjusted by tuning the AM process parameters. The Zn-3Mg specimens also exhibited improved biocompatibility as compared to pure Zn, including higher metabolic activity and enhanced osteogenic behavior of MC3T3 cells cultured with the extracts from the Zn-3Mg alloy specimens. Altogether, these results marked major progress in developing AM porous biodegradable metallic bone substitutes, which paved the way toward clinical adoption of Zn-based scaffolds for the treatment of load-bearing bony defects. STATEMENT OF SIGNIFICANCE: Our study presents a significant advancement in the realm of biodegradable metallic bone substitutes through the development of an additively manufactured Zn-3Mg alloy. This novel alloy showcases refined grains and a distinctive microstructure, enabling the fabrication of functionally graded porous structures with mechanical properties resembling cortical bone. The achieved compressive yield strength and elastic modulus signify a critical leap toward mimicking the mechanical behavior of load-bearing bone. Moreover, our findings reveal tunable biodegradation rates and enhanced biocompatibility compared to pure Zn, emphasizing the potential clinical utility of Zn-based scaffolds for treating load-bearing bony defects. This breakthrough opens doors for the wider adoption of zinc-based materials in regenerative orthopedics.


Subject(s)
Alloys , Cortical Bone , Zinc , Alloys/chemistry , Alloys/pharmacology , Zinc/chemistry , Zinc/pharmacology , Animals , Mice , Cortical Bone/drug effects , Porosity , Magnesium/chemistry , Magnesium/pharmacology , Materials Testing , Compressive Strength , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Absorbable Implants , Elastic Modulus , Cell Line
19.
Int J Biol Macromol ; 272(Pt 2): 132747, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38821301

ABSTRACT

Degradable magnesium alloy stents are considered to be ideal candidates to replace the traditional non-degradable stents for the treatment of cardiovascular diseases. However, bare magnesium alloy stents usually degrade too fast and show poor hemocompatibility and cytocompatibility, which seriously affects their clinical use. In this study, surface modification based on the MgF2 layer, polydopamine (PDA) coating, fucoidan and CAG peptides was performed on the Mg-Zn-Y-Nd (ZE21B) magnesium alloy with the purpose of improving its corrosion resistance, hemocompatibility and cytocompatibility for vascular stent application. After modification, the ZE21B alloy showed better corrosion resistance. Moreover, the lower hemolysis rate, platelet adhesion and activation, and fibrinogen adsorption and denaturation proved the improved hemocompatibility of modified ZE21B alloy in in vitro blood experiments. Furthermore, the co-immobilization of fucoidan and CAG peptides significantly promoted the adhesion, proliferation, migration and NO release of endothelial cells (ECs) on the modified ZE21B alloy, and meanwhile the modification with fucoidan and CAG peptides inhibited the adhesion and proliferation of smooth muscle cells (SMCs) and suppressed the expression of proinflammatory factors in the macrophages (MAs). The surface modification obviously enhanced the corrosion resistance, hemocompatibility and cytocompatibility of ZE21B alloy, and provided an effective strategy for the development of degradable vascular stents.


Subject(s)
Alloys , Cell Adhesion , Magnesium , Materials Testing , Peptides , Polysaccharides , Alloys/chemistry , Alloys/pharmacology , Polysaccharides/chemistry , Polysaccharides/pharmacology , Humans , Peptides/chemistry , Peptides/pharmacology , Magnesium/chemistry , Cell Adhesion/drug effects , Animals , Cell Proliferation/drug effects , Hemolysis/drug effects , Corrosion , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Platelet Adhesiveness/drug effects , Mice , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/metabolism , Human Umbilical Vein Endothelial Cells/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Surface Properties , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Aquatic Organisms/chemistry , Indoles , Polymers
20.
Adv Mater ; 36(29): e2401361, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38721975

ABSTRACT

Senescence plays a critical role in the development and progression of various diseases. This study introduces an amorphous, high-entropy alloy (HEA)-based nanozyme designed to combat senescence. By adjusting the nanozyme's composition and surface properties, this work analyzes its catalytic performance under both normal and aging conditions, confirming that peroxide and superoxide dismutase (SOD) activity are crucial for its anti-aging therapeutic function. Subsequently, the chiral-dependent therapeutic effect is validated and the senolytic performance of D-handed PtPd2CuFe across several aging models is confirmed. Through multi-Omics analyses, this work explores the mechanism underlying the senolytic action exerted by nanozyme in depth. It is confirm that exposure to senescent conditions leads to the enrichment of copper and iron atoms in their lower oxidation states, disrupting the iron-thiol cluster in mitochondria and lipoic acid transferase, as well as oxidizing unsaturated fatty acids, triggering a cascade of cuproptosis and ferroptosis. Additionally, the concentration-dependent anti-aging effects of nanozyme is validated. Even an ultralow dose, the therapeutic can still act as a senomorphic, reducing the effects of senescence. Given its broad-spectrum action and concentration-adjustable anti-aging potential, this work confirms the remarkable therapeutic capability of D-handed PtPd2CuFe in managing atherosclerosis, a disease involving various types of senescent cells.


Subject(s)
Atherosclerosis , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Humans , Animals , Mice , Copper/chemistry , Copper/pharmacology , Alloys/chemistry , Alloys/pharmacology , Iron/chemistry , Superoxide Dismutase/metabolism , Cellular Senescence/drug effects , Ferroptosis/drug effects
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