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1.
ACS Appl Mater Interfaces ; 16(19): 24274-24294, 2024 May 15.
Article En | MEDLINE | ID: mdl-38699930

In the field of bone tissue engineering, recently developed Zn alloy scaffolds are considered potential candidates for biodegradable implants for bone regeneration and defect reconstruction. However, the clinical success of these alloys is limited due to their insufficient surface bioactivities. Further, the higher concentration of Zn2+ produced during degradation promotes antibacterial activity, but deteriorates osteogenic properties. This study fabricated an Azadirachta indica (neem)-assisted brushite-hydroxyapatite (HAp) coating on the recently developed Zn-2Cu-0.5Mg alloy to tackle the above dilemma. The microstructure, degradation behavior, antibacterial activity, and hemocompatibility, along with in vitro and in vivo cytocompatibility of the coated alloys, are systematically investigated. Microstructural analysis reveals flower-like morphology with uniformly grown flakes for neem-assisted deposition. The neem-assisted deposition significantly improves the adhesion strength from 12.7 to 18.8 MPa, enhancing the mechanical integrity. The potentiodynamic polarization study shows that the neem-assisted deposition decreases the degradation rate, with the lowest degradation rate of 0.027 mm/yr for the ZHN2 sample. In addition, the biomineralization process shows the apatite formation on the deposited coating after 21 days of immersion. In vitro cytotoxicity assay exhibits the maximum cell viability of 117% for neem-assisted coated alloy in 30% extract after 5d and the improved cytocompatibility which is due to the controlled release of Zn2+ ions. Meanwhile, neem-assisted coated alloy increases the ZOI by 32 and 24% for Gram-positive and Gram-negative bacteria, respectively. Acceptable hemolysis (<5%) and anticoagulation parameters demonstrate a promising hemocompatibility of the coated alloy. In vivo implantation illustrates a slight inflammatory response and vascularization after 2 weeks of subcutaneous implantation, and neo-bone formation in the defect areas of the rat femur. Micro-CT and histology studies demonstrate better osseointegration with satisfactory biosafety response for the neem-assisted coated alloy as compared to that without neem-assisted deposition. Hence, this neem-assisted brushite-Hap coating strategy elucidates a new perspective on the surface modification of biodegradable implants for the treatment of bone defects.


Alloys , Calcium Phosphates , Coated Materials, Biocompatible , Zinc , Alloys/chemistry , Alloys/pharmacology , Zinc/chemistry , Zinc/pharmacology , Animals , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Humans , Durapatite/chemistry , Durapatite/pharmacology , Materials Testing , Mice , Green Chemistry Technology , Absorbable Implants
2.
ACS Appl Mater Interfaces ; 16(19): 24321-24340, 2024 May 15.
Article En | MEDLINE | ID: mdl-38700914

In current clinical practices related to orthopedics, dental, and cardiovascular surgeries, a number of biomaterial coatings, such as hydroxyapatite (HAp), diamond-like carbon (DLC), have been used in combination with metallic substrates (stainless steel, Ti6Al4V alloy, etc.). Although SiBCN coatings are widely explored in material science for diverse applications, their potential remains largely unexplored for biomedical applications. With this motivation, the present work reports the development of SiBxCyNzOm coatings on a Ti6Al4V substrate, employing a reactive radiofrequency (RF) magnetron sputtering technique. Three different coating compositions (Si0.27B0.10C0.31N0.07O0.24, Si0.23B0.06C0.21N0.22O0.27, and Si0.20B0.05C0.19N0.20O0.35) were obtained using a Si2BC2N target and varying nitrogen flow rates. The hydrophilic properties of the as-synthesized coatings were rationalized in terms of an increase in the number of oxygen-containing functional groups (OH and NO) on the surface, as probed using XPS and FTIR analyses. Furthermore, the cellular monoculture of SVEC4-10 endothelial cells and L929 fibroblasts established good cytocompatibility. More importantly, the coculture system of SVEC4-10 and L929, in the absence of growth factors, demonstrated clear cellular phenotypical changes, with extensive sprouting leading to tube-like morphologies on the coating surfaces, when stimulated using a customized cell stimulator (StimuCell) with 1.15 V/cm direct current (DC) electric field strength for 1 h. In addition, the hemocompatibility assessment using human blood samples revealed clinically acceptable hemolysis, less erythrocyte adhesion, shorter plasma recalcification, and reduced risk for thrombosis on the SiBxCyNzOm coatings, when compared to uncoated Ti6Al4V. Taken together, the present study unambiguously establishes excellent cytocompatibility, hemocompatibility, and defines the preangiogenic properties of SiBxCyNzOm bioceramic coatings for potential biomedical applications.


Alloys , Coated Materials, Biocompatible , Materials Testing , Titanium , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Alloys/chemistry , Alloys/pharmacology , Titanium/chemistry , Titanium/pharmacology , Humans , Animals , Mice , Endothelial Cells/drug effects , Endothelial Cells/cytology , Cell Line , Surface Properties , Fibroblasts/drug effects , Fibroblasts/cytology , Neovascularization, Physiologic/drug effects
3.
Eur Rev Med Pharmacol Sci ; 28(9): 3391-3402, 2024 May.
Article En | MEDLINE | ID: mdl-38766802

OBJECTIVE: Although pure titanium (PT) and its alloys exhibit excellent mechanical properties, they lack biological activity as implants. The purpose of this study was to improve the biological activity of titanium implants through surface modification. MATERIALS AND METHODS: Titanium was processed into titanium discs, where the titanium discs served as anodes and stainless steel served as cathodes, and a copper- and cobalt-doped porous coating [pure titanium model (PTM)] was prepared on the surface of titanium via plasma electrolytic oxidation. The surface characteristics of the coating were evaluated using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and profilometry. The corrosion resistance of PTM was evaluated with an electrochemical workstation. The biocompatibility and bioactivity of coated bone marrow mesenchymal stem cells (BMSCs) were evaluated through in vitro cell experiments. RESULTS: A copper- and cobalt-doped porous coating was successfully prepared on the surface of titanium, and the doping of copper and cobalt did not change the surface topography of the coating. The porous coating increased the surface roughness of titanium and improved its resistance to corrosion. In addition, the porous coating doped with copper and cobalt promoted the adhesion and spreading of BMSCs. CONCLUSIONS: A porous coating doped with copper and cobalt was prepared on the surface of titanium through plasma electrolytic oxidation. The coating not only improved the roughness and corrosion resistance of titanium but also exhibited good biological activity.


Coated Materials, Biocompatible , Cobalt , Copper , Mesenchymal Stem Cells , Surface Properties , Titanium , Titanium/chemistry , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Mesenchymal Stem Cells/drug effects , Copper/chemistry , Porosity , Cobalt/chemistry , Animals , Corrosion , Materials Testing , Cells, Cultured , Prostheses and Implants
4.
Biomed Mater ; 19(4)2024 May 22.
Article En | MEDLINE | ID: mdl-38740037

The purpose of this study was to construct a rutin-controlled release system on the surface of Ti substrates and investigate its effects on osteogenesis and osseointegration on the surface of implants. The base layer, polyethylenimine (PEI), was immobilised on a titanium substrate. Then, hyaluronic acid (HA)/chitosan (CS)-rutin (RT) multilayer films were assembled on the PEI using layer-by-layer (LBL) assembly technology. We used scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and contact angle measurements to examine all Ti samples. The drug release test of rutin was also carried out to detect the slow-release performance. The osteogenic abilities of the samples were evaluated by experiments on an osteoporosis rat model and MC3T3-E1 cells. The results (SEM, FTIR and contact angle measurements) all confirmed that the PEI substrate layer and HA/CS-RT multilayer film were effectively immobilised on titanium. The drug release test revealed that a rutin controlled release mechanism had been successfully established. Furthermore, thein vitrodata revealed that osteoblasts on the coated titanium matrix had greater adhesion, proliferation, and differentiation capacity than the osteoblasts on the pure titanium surface. When MC3T3-E1 cells were exposed to H2O2-induced oxidative stressin vitro, cell-based tests revealed great tolerance and increased osteogenic potential on HA/CS-RT substrates. We also found that the HA/CS-RT coating significantly increased the new bone mass around the implant. The LBL-deposited HA/CS-RT multilayer coating on the titanium base surface established an excellent rutin-controlled release system, which significantly improved osseointegration and promoted osteogenesis under oxidative stress conditions, suggesting a new implant therapy strategy for patients with osteoporosis.


Coated Materials, Biocompatible , Hyaluronic Acid , Osseointegration , Osteoblasts , Osteogenesis , Osteoporosis , Prostheses and Implants , Rutin , Surface Properties , Titanium , Animals , Titanium/chemistry , Rutin/chemistry , Rutin/pharmacology , Osteogenesis/drug effects , Rats , Osteoporosis/drug therapy , Mice , Osteoblasts/drug effects , Osteoblasts/cytology , Osteoblasts/metabolism , Osseointegration/drug effects , Hyaluronic Acid/chemistry , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Oxidation-Reduction , Chitosan/chemistry , Female , Rats, Sprague-Dawley , Cell Adhesion/drug effects , Spectroscopy, Fourier Transform Infrared , Cell Differentiation/drug effects , Microscopy, Electron, Scanning , Cell Proliferation/drug effects , Polyethyleneimine/chemistry , 3T3 Cells , Oxidative Stress/drug effects , Layer-by-Layer Nanoparticles
5.
J Dent ; 145: 105033, 2024 Jun.
Article En | MEDLINE | ID: mdl-38697505

OBJECTIVES: This study aimed to enhance gingival fibroblast function and to achieve antibacterial activity around the implant abutment by using a zinc (Zn)-containing bioactive glass (BG) coating. METHODS: 45S5 BG containing 0, 5, and 10 wt.% Zn were coated on zirconia disks. The release of silica and Zn ions in physiological saline and their antibacterial effects were measured. The effects of BG coatings on human gingival fibroblasts (hGFs) were assessed using cytotoxicity assays and by analyzing the gene expression of various genes related to antioxidant enzymes, wound healing, and fibrosis. RESULTS: BG coatings are capable of continuous degradation and simultaneous ion release. The antibacterial effect of BG coatings increased with the addition of Zn, while the cytotoxicity remained unchanged compared to the group without coatings. BG coating enhances the expression of angiogenesis genes, while the Zn-containing BG enhances the expression of antioxidant genes at an early time point. BG coating enhances the expression of collagen genes at later time points. CONCLUSIONS: The antibacterial effect of BG improved with the increase in Zn concentration, without inducing cytotoxicity. BG coating enhances the expression of angiogenesis genes, and Zn-containing BG enhances the expression of antioxidant genes at an early time point. BG coating enhances the expression of collagen genes at later time points. CLINICAL SIGNIFICANCE: Adding 10 wt% Zn to BG could enhance the environment around implant abutments by providing antibacterial, antioxidant, and anti-fibrotic effects, having potential for clinical use.


Anti-Bacterial Agents , Ceramics , Dental Abutments , Fibroblasts , Gingiva , Glass , Surface Properties , Zinc , Zirconium , Zirconium/pharmacology , Zirconium/chemistry , Humans , Zinc/pharmacology , Fibroblasts/drug effects , Anti-Bacterial Agents/pharmacology , Gingiva/cytology , Gingiva/drug effects , Glass/chemistry , Ceramics/pharmacology , Ceramics/chemistry , Coated Materials, Biocompatible/pharmacology , Coated Materials, Biocompatible/chemistry , Antioxidants/pharmacology , Materials Testing , Collagen , Wound Healing/drug effects , Dental Materials/pharmacology , Dental Materials/chemistry , Cells, Cultured
6.
ACS Appl Bio Mater ; 7(5): 2872-2886, 2024 May 20.
Article En | MEDLINE | ID: mdl-38721671

Antimicrobial coatings provide protection against microbes colonization on surfaces. This can prevent the stabilization and proliferation of microorganisms. The ever-increasing levels of microbial resistance to antimicrobials are urging the development of alternative types of compounds that are potent across broad spectra of microorganisms and target different pathways. This will help to slow down the development of resistance and ideally halt it. The development of composite antimicrobial coatings (CACs) that can host and protect various antimicrobial agents and release them on demand is an approach to address this urgent need. In this work, new CACs based on microsized hybrids of calcium carbonate (CaCO3) and silver nanoparticles (AgNPs) were designed using a drop-casting technique. Polyvinylpyrrolidone and mucin were used as additives. The CaCO3/AgNPs hybrids contributed to endowing colloidal stability to the AgNPs and controlling their release, thereby ensuring the antibacterial activity of the coatings. Moreover, the additives PVP and mucin served as a matrix to (i) control the distribution of the hybrids, (ii) ensure mechanical integrity, and (iii) prevent the undesired release of AgNPs. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) techniques were used to characterize the 15 µm thick CAC. The antibacterial activity was determined against Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa, three bacteria responsible for many healthcare infections. Antibacterial performance of the hybrids was demonstrated at concentrations between 15 and 30 µg/cm2. Unloaded CaCO3 also presented bactericidal properties against MRSA. In vitro cytotoxicity tests demonstrated that the hybrids at bactericidal concentrations did not affect human dermal fibroblasts and human mesenchymal stem cell viability. In conclusion, this work presents a simple approach for the design and testing of advanced multicomponent and functional antimicrobial coatings that can protect active agents and release them on demand.


Anti-Bacterial Agents , Calcium Carbonate , Materials Testing , Metal Nanoparticles , Microbial Sensitivity Tests , Particle Size , Silver , Calcium Carbonate/chemistry , Calcium Carbonate/pharmacology , Silver/chemistry , Silver/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Metal Nanoparticles/chemistry , Humans , Cell Survival/drug effects , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Escherichia coli/drug effects , Surface Properties , Staphylococcus aureus/drug effects
7.
ACS Appl Bio Mater ; 7(5): 3283-3294, 2024 May 20.
Article En | MEDLINE | ID: mdl-38727030

Medical implants are constantly facing the risk of bacterial infections, especially infections caused by multidrug resistant bacteria. To mitigate this problem, gold nanoparticles with alkyl bromide moieties (Au NPs-Br) on the surfaces were prepared. Xenon light irradiation triggered the plasmon effect of Au NPs-Br to induce free radical graft polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA), leading to the formation of poly(DMAEMA) brush-grafted Au NPs (Au NPs-g-PDM). The Au NPs-g-PDM nanocomposites were conjugated with phytic acid (PA) via electrostatic interaction and van der Waals interaction. The as-formed aggregates were deposited on the titanium (Ti) substrates to form the PA/Au NPs-g-PDM (PAP) hybrid coatings through surface adherence of PA and the gravitational effect. Synergistic bactericidal effects of contact-killing caused by the cationic PDM brushes, and local heating generated by the Au NPs under near-infrared irradiation, conferred strong antibacterial effects on the PAP-deposited Ti (Ti-PAP) substrates. The synergistic bactericidal effects reduced the threshold temperature required for the photothermal sterilization, which in turn minimized the secondary damage to the implant site. The Ti-PAP substrates exhibited 97.34% and 99.97% antibacterial and antiadhesive efficacy, respectively, against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), compared to the control under in vitro antimicrobial assays. Furthermore, the as-constructed Ti-PAP surface exhibited a 99.42% reduction in the inoculated S. aureus under in vivo assays. In addition, the PAP coatings exhibited good biocompatibility in the hemolysis and cytotoxicity assays as well as in the subcutaneous implantation of rats.


Anti-Bacterial Agents , Escherichia coli , Gold , Materials Testing , Metal Nanoparticles , Microbial Sensitivity Tests , Particle Size , Phytic Acid , Staphylococcus aureus , Gold/chemistry , Gold/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Metal Nanoparticles/chemistry , Phytic Acid/chemistry , Phytic Acid/pharmacology , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Animals , Surface Properties , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Cations/chemistry , Cations/pharmacology , Polymers/chemistry , Polymers/pharmacology , Titanium/chemistry , Titanium/pharmacology
8.
Clin Oral Investig ; 28(6): 323, 2024 May 18.
Article En | MEDLINE | ID: mdl-38761310

OBJECTIVES: White spot lesions are the most common iatrogenic effect observed during orthodontic treatment. This study aimed to compare the surface characteristics and antibacterial action of uncoated and coated orthodontic brackets. MATERIALS AND METHODS: Sixty commercially available stainless steel brackets were coated with TiO2 nanotubes and methacryloyloxyethylphosphorylcholine. The sample was divided into Group 1: uncoated orthodontic brackets, Group 2: Stainless steel brackets with TiO2 nanotubes coating, Group 3: Stainless steel brackets with methacryloyloxyethylphosphorylcholine coating, and Group 4: Stainless steel brackets with TiO2 nanotubes combined with methacryloyloxyethylphosphorylcholine coating. Surface characterization was assessed using atomic force microscopy and scanning electron microscopy. Streptococcus mutans was selected to test the antibacterial ability of the orthodontic brackets, total bacterial adhesion and bacterial viability were assessed. The brackets were subjected to scanning electron microscopy to detect the presence of biofilm. RESULTS: The surface roughness was the greatest in Group 1 and least in Group 2 followed by Group 4 and Group 3 coated brackets. The optical density values were highest in Group 1 and lowest in Group 4. Comparison of colony counts revealed high counts in Group 1 and low counts in Group 4. A positive correlation between surface roughness and colony counts was obtained, however, was not statistically significant. CONCLUSIONS: The coated orthodontic brackets exhibited less surface roughness than the uncoated orthodontic brackets. Group 4 coated orthodontic brackets showed the best antibacterial properties. CLINICAL RELEVANCE: Coated orthodontic brackets prevent adhesion of streptococcus mutans and reduces plaque accumulation around the brackets thereby preventing formation of white spot lesions during orthodontic treatment.


Anti-Bacterial Agents , Bacterial Adhesion , Microscopy, Electron, Scanning , Nanotubes , Orthodontic Brackets , Phosphorylcholine , Streptococcus mutans , Surface Properties , Titanium , Titanium/chemistry , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/pharmacology , Phosphorylcholine/chemistry , Streptococcus mutans/drug effects , Anti-Bacterial Agents/pharmacology , Nanotubes/chemistry , Bacterial Adhesion/drug effects , Microscopy, Atomic Force , Materials Testing , Stainless Steel/chemistry , Methacrylates/pharmacology , Methacrylates/chemistry , Biofilms/drug effects , Coated Materials, Biocompatible/pharmacology , Coated Materials, Biocompatible/chemistry
9.
ACS Appl Mater Interfaces ; 16(19): 24421-24430, 2024 May 15.
Article En | MEDLINE | ID: mdl-38690964

Periprosthetic infections caused by Staphylococcus aureus (S. aureus) pose unique challenges in orthopedic surgeries, in part due to the bacterium's capacity to invade surrounding bone tissues besides forming recalcitrant biofilms on implant surfaces. We previously developed prophylactic implant coatings for the on-demand release of vancomycin, triggered by the cleavage of an oligonucleotide (Oligo) linker by micrococcal nuclease (MN) secreted by the Gram-positive bacterium, to eradicate S. aureus surrounding the implant in vitro and in vivo. Building upon this coating platform, here we explore the feasibility of extending the on-demand release to ampicillin, a broad-spectrum aminopenicillin ß-lactam antibiotic that is more effective than vancomycin in killing Gram-negative bacteria that may accompany S. aureus infections. The amino group of ampicillin was successfully conjugated to the carboxyl end of an MN-sensitive Oligo covalently integrated in a polymethacrylate hydrogel coating applied to titanium alloy pins. The resultant Oligo-Ampicillin hydrogel coating released the ß-lactam in the presence of S. aureus and successfully cleared nearby S. aureus in vitro. When the Oligo-Ampicillin-coated pin was delivered to a rat femoral canal inoculated with 1000 cfu S. aureus, it prevented periprosthetic infection with timely on-demand drug release. The clearance of the bacteria from the pin surface as well as surrounding tissue persisted over 3 months, with no local or systemic toxicity observed with the coating. The negatively charged Oligo fragment attached to ampicillin upon cleavage from the coating did diminish the antibiotic's potency against S. aureus and Escherichia coli (E. coli) to varying degrees, likely due to electrostatic repulsion by the anionic surfaces of the bacteria. Although the on-demand release of the ß-lactam led to adequate killing of S. aureus but not E. coli in the presence of a mixture of the bacteria, strong inhibition of the colonization of the remaining E. coli on hydrogel coating was observed. These findings will inspire considerations of alternative broad-spectrum antibiotics, optimized drug conjugation, and Oligo linker engineering for more effective protection against polymicrobial periprosthetic infections.


Ampicillin , Anti-Bacterial Agents , Coated Materials, Biocompatible , Prosthesis-Related Infections , Staphylococcal Infections , Staphylococcus aureus , Animals , Staphylococcus aureus/drug effects , Ampicillin/chemistry , Ampicillin/pharmacology , Rats , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Staphylococcal Infections/prevention & control , Staphylococcal Infections/drug therapy , Prosthesis-Related Infections/prevention & control , Prosthesis-Related Infections/drug therapy , Prosthesis-Related Infections/microbiology , Rats, Sprague-Dawley , Microbial Sensitivity Tests , Drug Liberation , Prostheses and Implants
10.
Sci Rep ; 14(1): 7624, 2024 04 01.
Article En | MEDLINE | ID: mdl-38561345

It is known that titanium (Ti) implant surfaces exhibit poor antibacterial properties and osteogenesis. In this study, chitosan particles loaded with aspirin, amoxicillin or aspirin + amoxicillin were synthesized and coated onto implant surfaces. In addition to analysing the surface characteristics of the modified Ti surfaces, the effects of the modified Ti surfaces on the adhesion and viability of rat bone marrow-derived stem cells (rBMSCs) were evaluated. The metabolic activities of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) biofilms on the modified Ti surfaces were also measured in vitro. Moreover, S. aureus was tested for its antibacterial effect by coating it in vivo. Using water as the droplet medium, the contact angles of the modified Ti surfaces increased from 44.12 ± 1.75° to 58.37 ± 4.15°. In comparison to those of the other groups tested, significant increases in rBMSC adhesion and proliferation were observed in the presence of aspirin + amoxicillin-loaded microspheres, whereas a significant reduction in the metabolic level of biofilms was observed in the presence of aspirin + amoxicillin-loaded microspheres both in vitro and in vivo. Aspirin and amoxicillin could be used in combination to coat implant surfaces to mitigate bacterial activities and promote osteogenesis.


Amoxicillin , Chitosan , Indoles , Polymers , Rats , Animals , Amoxicillin/pharmacology , Aspirin/pharmacology , Titanium/pharmacology , Chitosan/pharmacology , Osteogenesis , Staphylococcus aureus , Escherichia coli , Anti-Bacterial Agents/pharmacology , Surface Properties , Coated Materials, Biocompatible/pharmacology
11.
ACS Appl Mater Interfaces ; 16(17): 21672-21688, 2024 May 01.
Article En | MEDLINE | ID: mdl-38637290

Titanium (Ti) and its alloys are widely used as hard tissue substitutes in dentistry and orthopedics, but their low bioactivity leads to undesirable osseointegration defects in the early osteogenic phase. Surface modification is an important approach to overcome these problems. In the present study, novel magnesium phosphate (MgP) coatings with controllable structures were fabricated on the surface of Ti using the phosphate chemical conversion (PCC) method. The effects of the microstructure on the physicochemical and biological properties of the coatings on Ti were researched. The results indicated that accelerators in PCC solution were important factors affecting the microstructure and properties of the MgP coatings. In addition, the coated Ti exhibited excellent hydrophilicity, high bonding strength, and good corrosion resistance. Moreover, the biological results showed that the MgP coatings could improve the spread, proliferation, and osteogenic differentiation of mouse osteoblast cells (MC3T3-E1) and vascular differentiation of human umbilical vein endothelial cells (HUVECs), indicating that the coated Ti samples had a great effect on promoting osteogenesis and angiogenesis. Overall, this study provided a new research idea for the surface modification of conventional Ti to enhance osteogenesis and angiogenesis in different bone types for potential biomedical applications.


Cell Differentiation , Cell Proliferation , Coated Materials, Biocompatible , Human Umbilical Vein Endothelial Cells , Magnesium Compounds , Neovascularization, Physiologic , Osteogenesis , Phosphates , Titanium , Titanium/chemistry , Titanium/pharmacology , Osteogenesis/drug effects , Animals , Mice , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Phosphates/chemistry , Phosphates/pharmacology , Magnesium Compounds/chemistry , Magnesium Compounds/pharmacology , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Neovascularization, Physiologic/drug effects , Osteoblasts/drug effects , Osteoblasts/cytology , Surface Properties , Cell Line , Angiogenesis
12.
Colloids Surf B Biointerfaces ; 238: 113916, 2024 Jun.
Article En | MEDLINE | ID: mdl-38636438

The ureteral stent is an effective treatment for clinical ureteral stricture following urological surgery, and the functional coating of the stent could effectively inhibit bacterial colonization and other complications. The present review provides an analysis and description of the materials used in ureteral stents and their coatings. Emphasis is placed on the technological advancements of functional coatings, taking into consideration the characteristics of these materials and the properties of their active substances. Furthermore, recent advances in enhancing the therapeutic efficacy of functional coatings are also reviewed. It is anticipated that this article will serve as a valuable reference providing insights for future research development on new drug-loaded ureteral stents.


Coated Materials, Biocompatible , Polymers , Stents , Ureter , Humans , Ureter/surgery , Polymers/chemistry , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Animals
13.
Colloids Surf B Biointerfaces ; 238: 113914, 2024 Jun.
Article En | MEDLINE | ID: mdl-38663310

Combining with various antibacterial mechanisms is the preferred strategy to fabricate coatings with effective antibacterial performance. Herein, Cu2O nanoparticles and dimethyloctadecyl [3-(trimethoxysilyl) propyl] ammonium chloride, a kind of quaternary ammonium salt (QAS), were simultaneously incorporated into a moisture-curable acrylic resin in order to achieve both contact-killing and release-killing abilities for antibacterial coatings. The surface morphology, surface composition and basic properties of the coatings were thoroughly characterized. The antibacterial performance of the coatings was determined by in-vitro bacteriostatic test. Under the constant total mass fraction of antibacterial agents, both Cu2O and QAS content possessed the highest value on the coating surface at Cu2O/QAS mass ratio of 1:1, and correspondingly, the coatings reached sterilizing rate above 99 % against both E. coli and S. loihica, indicating the existence of synergistic effect between Cu2O and QAS. The synergistic antibacterial mechanism of the coatings involved two aspects. Firstly, the combination of contact-killing and release-killing biocides resulted in high bactericidal and antibiofilm activity against different bacteria. Further, the grafting of QAS molecules on the surface of Cu2O particles brought about the spontaneous migration of nanoparticles to the coating surface. The interaction between Cu2O and QAS also inhibited the phase separation of QAS and prolonged the release of Cu2+ at the same time. The coatings, therefore, exhibited stable antibacterial performance at varied service conditions.


Anti-Bacterial Agents , Copper , Escherichia coli , Microbial Sensitivity Tests , Quaternary Ammonium Compounds , Surface Properties , Copper/chemistry , Copper/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology , Escherichia coli/drug effects , Particle Size , Nanoparticles/chemistry , Metal Nanoparticles/chemistry , Acrylic Resins/chemistry , Acrylic Resins/pharmacology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology
14.
Colloids Surf B Biointerfaces ; 238: 113908, 2024 Jun.
Article En | MEDLINE | ID: mdl-38677153

In response to the critical demand for advancements in coronary artery stents, this study addresses the challenges associated with arterial recoil and restenosis post-angioplasty and the imperative to encourage rapid re-endothelialization for minimizing thrombosis risks. We employed an innovative approach inspired by mussel adhesion, incorporating placental anticoagulant protein (AnnexinV) on stent design. The introduction of a post-translationally modified catecholic amino acid L-3,4-dihydroxyphenylalanine (L-Dopa), mimicking mussel characteristics, allowed for effective surface modification of Stainless steel stents through genetic code engineering in AnnexinV (AnxDopa). The efficacy of AnxDopa was analyzed through microscale thermophoresis and flow cytometry, confirming AnxDopa's exceptional binding with phosphatidylserine and activated platelets. AnxDopa coated stainless steel demonstrates remarkable bio-, hemo-, and immuno-compatibility, preventing smooth muscle cell proliferation, platelet adhesion, and fibrin formation. It acts as an interface between the stent and biological fluid, which facilitates the anticoagulation and rapid endothelialization. Surface modification of SS verified through XPS analysis and contact angle measurement attests to the efficacy of AnxDopa mediated surface modification. The hydrophilic nature of the AnxDopa-coated surface enhanced the endothelialization through increased protein absorption. This approach represents a significant stride in developing coronary stents with improved biocompatibility and reduced restenosis risks, offering valuable contributions to scientific and clinical realms alike.


Coated Materials, Biocompatible , Stents , Humans , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Coronary Vessels/drug effects , Platelet Adhesiveness/drug effects , Anticoagulants/pharmacology , Anticoagulants/chemistry , Surface Properties , Cell Proliferation/drug effects , Stainless Steel/chemistry , Blood Platelets/drug effects , Blood Platelets/metabolism , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/cytology , Animals , Levodopa/chemistry , Levodopa/pharmacology
15.
Acta Biomater ; 180: 358-371, 2024 May.
Article En | MEDLINE | ID: mdl-38604464

Glaucoma valves (GVs) play an essential role in treating glaucoma. However, fibrosis after implantation has limited their long-term success in clinical applications. In this study, we aimed to develop a comprehensive surface-engineering strategy to improve the biocompatibility of GVs by constructing a microenvironment-regulated and dual-hydrophilic antifouling coating on a GV material (silicone rubber, SR). The coating was based on a superhydrophilic polydopamine (SPD) coating with good short-range superhydrophilicity and antifouling abilities. In addition, SPD coatings contain many phenolic hydroxyl groups that can effectively resist oxidative stress and the inflammatory microenvironment. Furthermore, based on its in situ photocatalytic free-radical polymerization properties, the SPD coating polymerized poly 2-methylacryloxyethylphosphocholine, providing an additional long-range hydrophilic and antifouling effect. The in vitro test results showed that the microenvironment-regulated and dual-hydrophilic coatings had anti-protein contamination, anti-oxidation, anti-inflammation, and anti-fiber proliferation capabilities. The in vivo test results indicated that this coating substantially reduced the fiber encapsulation formation of the SR material by inhibiting inflammation and fibrosis. This design strategy for dual hydrophilic coatings with microenvironmental regulation can provide a valuable reference for the surface engineering design of novel medical implantable devices. STATEMENT OF SIGNIFICANCE: Superhydrophilic polydopamine (SPD) coatings were prepared on silicone rubber (SR) by a two-electron oxidation method. Introduction of pMPC to SPD surface using photocatalytic radical polymerization to obtain a dual-hydrophilic coating. The dual-hydrophilic coating effectively modulates the oxidative and inflammatory microenvironment. This coating significantly reduced protein contamination and adhesion of inflammatory cells and fibroblasts in vitro. The coating-modified SR inhibits inflammatory and fibrosis responses in vivo, promising to serve the glaucoma valves.


Coated Materials, Biocompatible , Glaucoma Drainage Implants , Hydrophobic and Hydrophilic Interactions , Polymers , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Animals , Polymers/chemistry , Polymers/pharmacology , Indoles/chemistry , Indoles/pharmacology , Surface Properties , Humans , Glaucoma/pathology
16.
Acta Biomater ; 180: 183-196, 2024 May.
Article En | MEDLINE | ID: mdl-38604465

The utilization of biodegradable magnesium (Mg) alloys in the fabrication of temporary non-vascular stents is an innovative trend in biomedical engineering. However, the heterogeneous degradation profiles of these biomaterials, together with potential bacterial colonization that could precipitate infectious or stenotic complications, are critical obstacles precluding their widespread clinical application. In pursuit of overcoming these limitations, this study applies the principles of biomimicry, particularly the hydrophobic and anti-fouling characteristics of lotus leaves, to pioneer the creation of nanocomposite coatings. These coatings integrate poly-trimethylene carbonate (PTMC) with covalent organic frameworks (COFs), to modify the stent's surface property. The strategic design of the coating's topography, porosity, and self-polishing capabilities collectively aims to decelerate degradation processes and minimize biological adhesion. The protective qualities of the coatings were substantiated through rigorous testing in both in vitro dynamic bile tests and in vivo New Zealand rabbit choledochal models. Empirical findings from these trials confirmed that the implementation of COF-based nanocomposite coatings robustly fortifies Mg implantations, conferring heightened resistance to both biocorrosion and biofouling as well as improved biocompatibility within bodily environments. The outcomes of this research elucidate a comprehensive framework for the multifaceted strategies against stent corrosion and fouling, thereby charting a visionary pathway toward the systematic conception of a new class of reliable COF-derived surface modifications poised to amplify the efficacy of Mg-based stents. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium (Mg) alloys are widely utilized in temporary stents, though their rapid degradation and susceptibility to bacterial infection pose significant challenges. Our research has developed a nanocomposite coating inspired by the lotus, integrating poly-trimethylene carbonate with covalent organic frameworks (COF). The coating achieved self-polishing property and optimal surface energy on the Mg substrate, which decelerates stent degradation and reduces biofilm formation. Comprehensive evaluations utilizing dynamic bile simulations and implantation in New Zealand rabbit choledochal models reveal that the coating improves the durability and longevity of the stent. The implications of these findings suggest the potential COF-based Mg alloy stent surface treatments and a leap forward in advancing stent performance and endurance in clinical applications.


Absorbable Implants , Coated Materials, Biocompatible , Magnesium , Nanocomposites , Stents , Animals , Rabbits , Magnesium/chemistry , Magnesium/pharmacology , Nanocomposites/chemistry , Corrosion , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Biofouling/prevention & control , Dioxanes/chemistry , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Polymers/chemistry , Polymers/pharmacology , Alloys/chemistry , Alloys/pharmacology
17.
Biomacromolecules ; 25(5): 3098-3111, 2024 May 13.
Article En | MEDLINE | ID: mdl-38606583

Biodegradable stents are the most promising alternatives for the treatment of cardiovascular disease nowadays, and the strategy of preparing functional coatings on the surface is highly anticipated for addressing adverse effects such as in-stent restenosis and stent thrombosis. Yet, inadequate mechanical stability and biomultifunctionality limit their clinical application. In this study, we developed a multicross-linking hydrogel on the polylactic acid substrates by dip coating that boasts impressive antithrombotic ability, antibacterial capability, mechanical stability, and self-healing ability. Gelatin methacryloyl, carboxymethyl chitosan, and oxidized sodium alginate construct a double-cross-linking hydrogel through the dynamic Schiff base chemical and in situ blue initiation reaction. Inspired by the adhesion mechanism employed by mussels, a triple-cross-linked hydrogel is formed with the addition of tannic acid to increase the adhesion and antibiofouling properties. The strength and hydrophilicity of hydrogel coating are regulated by changing the composition ratio and cross-linking degree. It has been demonstrated in tests in vitro that the hydrogel coating significantly reduces the adhesion of proteins, MC3T3-E1 cells, platelets, and bacteria by 85% and minimizes the formation of blood clots. The hydrogel coating also exhibits excellent antimicrobial in vitro and antiinflammatory properties in vivo, indicating its potential value in vascular intervention and other biomedical fields.


Anti-Inflammatory Agents , Anticoagulants , Bivalvia , Polyesters , Stents , Animals , Bivalvia/chemistry , Mice , Polyesters/chemistry , Polyesters/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Stents/adverse effects , Anticoagulants/chemistry , Anticoagulants/pharmacology , Gelatin/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Chitosan/chemistry , Chitosan/analogs & derivatives , Chitosan/pharmacology , Alginates/chemistry , Alginates/pharmacology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Tannins/chemistry , Tannins/pharmacology , Humans , Methacrylates
18.
ACS Biomater Sci Eng ; 10(5): 3057-3068, 2024 May 13.
Article En | MEDLINE | ID: mdl-38641433

Blood-contacting catheters play a pivotal role in contemporary medical treatments, particularly in the management of cardiovascular diseases. However, these catheters exhibit inappropriate wettability and lack antimicrobial characteristics, which often lead to catheter-related infections and thrombosis. Therefore, there is an urgent need for blood contact catheters with antimicrobial and anticoagulant properties. In this study, we employed tannic acid (TA) and 3-aminopropyltriethoxysilane (APTES) to create a stable hydrophilic coating under mild conditions. Heparin (Hep) and poly(lysine) (PL) were then modified on the TA-APTES coating surface using the layer-by-layer (LBL) technique to create a superhydrophilic TA/APTES/(LBL)4 coating on silicone rubber (SR) catheters. Leveraging the superhydrophilic nature of this coating, it can be effectively applied to blood-contacting catheters to impart antibacterial, antiprotein adsorption, and anticoagulant properties. Due to Hep's anticoagulant attributes, the activated partial thromboplastin time and thrombin time tests conducted on SR/TA-APTES/(LBL)4 catheters revealed remarkable extensions of 276 and 103%, respectively, when compared to uncoated commercial SR catheters. Furthermore, the synergistic interaction between PL and TA serves to enhance the resistance of SR/TA-APTES/(LBL)4 catheters against bacterial adherence, reducing it by up to 99.9% compared to uncoated commercial SR catheters. Remarkably, the SR/TA-APTES/(LBL)4 catheter exhibits good biocompatibility with human umbilical vein endothelial cells in culture, positioning it as a promising solution to address the current challenges associated with blood-contact catheters.


Catheters , Coated Materials, Biocompatible , Heparin , Polyphenols , Tannins , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Humans , Catheters/microbiology , Polyphenols/chemistry , Polyphenols/pharmacology , Heparin/chemistry , Heparin/pharmacology , Tannins/chemistry , Tannins/pharmacology , Silanes/chemistry , Silanes/pharmacology , Anticoagulants/chemistry , Anticoagulants/pharmacology , Propylamines/chemistry , Amines/chemistry , Amines/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Polylysine/chemistry , Polylysine/pharmacology , Surface Properties , Hydrophobic and Hydrophilic Interactions , Human Umbilical Vein Endothelial Cells/drug effects , Silicone Elastomers/chemistry , Adsorption , Escherichia coli/drug effects
19.
Colloids Surf B Biointerfaces ; 238: 113880, 2024 Jun.
Article En | MEDLINE | ID: mdl-38581836

In the field of orthopedics, it's crucial to effectively slow down the degradation rate of Mg alloys. This study aims to improve the degradation behavior of Mg-Zn-Ca alloys by electrodepositing fluorohydroxyapatite (FHA). We investigated the microstructure and bond strength of the deposition, as well as degradation and cellular reactions. After 15-30 days of degradation in Hanks solution, FHA deposited alloys showed enhanced stability and less pH change. The strong interfacial bond between FHA and the Mg-Zn-Ca substrate was verified through scratch tests (Critical loads: 10.73 ± 0.014 N in Mg-Zn-0.5Ca alloys). Cellular studies demonstrated that FHA-coated alloys exhibited good cytocompatibility and promoted the growth of MC3T3-E1 cells. Further tests showed FHA-coated alloys owed improved early bone mineralization and osteogenic properties, especially in Mg-Zn-0.5Ca. This research highlighted the potential of FHA-coated Mg-Zn-0.5Ca alloys in orthopedics applications.


Alloys , Calcium , Magnesium , Zinc , Alloys/chemistry , Alloys/pharmacology , Corrosion , Animals , Zinc/chemistry , Zinc/pharmacology , Magnesium/chemistry , Mice , Calcium/chemistry , Calcium/metabolism , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Surface Properties , Materials Testing , Cell Proliferation/drug effects , Hydroxyapatites/chemistry , Cell Line , Durapatite/chemistry , Durapatite/pharmacology
20.
ACS Appl Mater Interfaces ; 16(19): 25194-25209, 2024 May 15.
Article En | MEDLINE | ID: mdl-38684227

The revolutionary self-healing function for long-term and safe service processes has inspired researchers to implement them in various fields, including in the application of antimicrobial protective coatings. Despite the great advances that have been made in the field of fabricating self-healing and antimicrobial polymers, their poor transparency and the trade-off between the mechanical and self-healing properties limit the utility of the materials as transparent antimicrobial protective coatings for wearable optical and display devices. Considering the compatibility in the blending process, our group proposed a self-healing, self-cross-linkable poly{(n-butyl acrylate)-co-[N-(hydroxymethyl)acrylamide]} copolymer (AP)-based protective coating combined with two types of commercial cationic antimicrobial agents (i.e., dimethyl octadecyl (3-trimethoxysilylpropyl) ammonium chloride (DTSACL) and chlorhexidine gluconate (CHG)), leading to the fabrication of a multifunctional modified compound film of (AP/b%CHG)-grafted-a%DTSACL. The first highlight of this research is that the reactivity of the hydroxyl group in the N-(hydroxymethyl)acrylamide of the copolymer side chains under thermal conditions facilitates the "grafting to" process with the trimethoxysilane groups of DTSACL to form AP-grafted-DTSACL, yielding favorable thermal stability, improvement in hydrophobicity, and enhancement of mechanical strength. Second, we highlight that the addition of CHG can generate covalent and noncovalent interactions in a complex manner between the two biguanide groups of CHG with the AP and DTSACL via a thermal-triggered cross-linking reaction. The noncovalent interactions synergistically serve as diverse dynamic hydrogen bonds, leading to complete healing upon scratches and even showing over 80% self-healing efficiency on full-cut, while covalent bonding can effectively improve elasticity and mechanical strength. The soft nature of CHG also takes part in improving the self-healing of the copolymer. Moreover, it was discovered that the addition of CHG can enhance antimicrobial effectiveness, as demonstrated by the long-term superior antibacterial activity (100%) against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria and the antifouling function on a glass substrate and/or a silica wafer coated by the modified polymer.


Polymers , Polymers/chemistry , Polymers/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Elasticity , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Chlorhexidine/chemistry , Chlorhexidine/pharmacology , Chlorhexidine/analogs & derivatives
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