Antimicrobial Brushes on Titanium via “Grafting to” Using Phosphonic Acid/Pyridinium Containing Block Copolymers

Coating medical implants with antibacterial polymers may prevent postoperative infections which are a common issue for conventional titanium implants and can even lead to implant failure. Easily applicable diblock copolymers are presented that form polymer brushes via “grafting to” mechanism on titanium and equip the modified material with antibacterial properties. The polymers carry quaternized pyridinium units to combat bacteria and phosphonic acid groups which allow the linear chains to be anchored to metal surfaces in a convenient coating process. The polymers are synthesized via reversible-addition-fragmentation-chain-transfer (RAFT) polymerization and postmodifications and are characterized using NMR spectroscopy and SEC. Low grafting densities are a major drawback of the “grafting to” approach compared to “grafting from”. Thus, the number of phosphonic acid groups in the anchor block are varied to investigate and optimize the surface binding. Modified titanium surfaces are examined regarding their composition, wetting behavior, streaming potential, and coating stability. Evaluation of the antimicrobial properties revealed reduced bacterial adhesion and biofilm formation for certain polymers, albeit the cell biocompatibility against human gingival fibroblasts is also impaired. The presented findings show the potential of easy-to-apply polymer coatings and aid in designing next-generation implant surface modifications.     

硬组织植入聚醚醚酮表面生物活性改性研究

介绍了有望替代传统医用金属材料用作硬组织植入体的特种工程塑料聚醚醚酮（PEEK）的一些优异特性及其不足。首先,综述了在PEEK表面构筑羟基磷灰石、钛或二氧化钛等改性涂层对体外及体内生物活性的影响,并重点强调了改性涂层与基底结合力的重要性。其次,综述了直接表面改性手段,如等离子体浸没离子注入、激光处理、湿法改性等在PEEK表面构筑有利的表面物理及化学性质,赋予其表面生物活性的研究进展。最后,对构筑兼具生物活性和抗菌活性的PEEK表面进行总结,并对其发展方向进行了展望。     

Introducing a Semi-Coated Model to Investigate Antibacterial Effects of Biocompatible Polymers on Titanium Surfaces

Peri-implant infections from bacterial biofilms on artificial surfaces are a common threat to all medical implants. They are a handicap for the patient and can lead to implant failure or even life-threatening complications. New implant surfaces have to be developed to reduce biofilm formation and to improve the long-term prognosis of medical implants. The aim of this study was (1) to develop a new method to test the antibacterial efficacy of implant surfaces by direct surface contact and (2) to elucidate whether an innovative antimicrobial copolymer coating of 4-vinyl-N-hexylpyridinium bromide and dimethyl(2-methacryloyloxyethyl) phosphonate (VP:DMMEP 30:70) on titanium is able to reduce the attachment of bacteria prevalent in peri-implant infections. With a new in vitro model with semi-coated titanium discs, we were able to show a dramatic reduction in the adhesion of various pathogenic bacteria (Streptococcus sanguinis, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis), completely independently of effects caused by soluble materials. In contrast, soft tissue cells (human gingival or dermis fibroblasts) were less affected by the same coating, despite a moderate reduction in initial adhesion of gingival fibroblasts. These data confirm the hypothesis that VP:DMMEP 30:70 is a promising antibacterial copolymer that may be of use in several clinical applications.     

Cerium-doped hydroxyapatite/collagen coatings on titanium for bone implants

The novelty of the present research consists in the possibility of obtaining cerium-doped hydroxyapatite/collagen coatings on the titanium support, to improve the performance of the bone implants. These coatings were deposited on the titanium surface by biomimetic method using a modified supersaturated calcification solution (SCS) additionally containing a cerium source and collagen. Prior to the deposition of the apatite layer, an alkali ÷ thermal oxidation pretreatment has been applied to ensure an increase in the bioactivity of the titanium surface. The coatings were examined by scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD) and Fourier transformed infrared (FTIR) spectroscopy. The EDX and XRD investigations of the coatings indicated that cerium was incorporated in the hydroxyapatite lattice. The collagen presence in the coatings was confirmed by FTIR analysis. The cerium-doped hydroxyapatite/collagen coatings showed good antibacterial efficacy against Escherichia coli and Staphylococcus aureus bacteria, being more effective against Escherichia coli. These coatings have a significant potential to be used in the dental and orthopedic implants, as the osseointegration depends on much more factors than simple formation of hydroxyapatite.     

Antibacterial Titanium Implants Biofunctionalized by Plasma Electrolytic Oxidation with Silver,Zinc, and Copper: A Systematic Review

Patients receiving orthopedic implants are at risk of implant-associated infections (IAI). A growing number of antibiotic-resistant bacteria threaten to hamper the treatment of IAI. The focus has, therefore, shifted towards the development of implants with intrinsic antibacterial activity to prevent the occurrence of infection. The use of Ag, Cu, and Zn has gained momentum as these elements display strong antibacterial behavior and target a wide spectrum of bacteria. In order to incorporate these elements into the surface of titanium-based bone implants, plasma electrolytic oxidation (PEO) has been widely investigated as a single-step process that can biofunctionalize these (highly porous) implant surfaces. Here, we present a systematic review of the studies published between 2009 until 2020 on the biomaterial properties, antibacterial behavior, and biocompatibility of titanium implants biofunctionalized by PEO using Ag, Cu, and Zn. We observed that 100% of surfaces bearing Ag (Ag-surfaces), 93% of surfaces bearing Cu (Cu-surfaces), 73% of surfaces bearing Zn (Zn-surfaces), and 100% of surfaces combining Ag, Cu, and Zn resulted in a significant (i.e., >50%) reduction of bacterial load, while 13% of Ag-surfaces, 10% of Cu-surfaces, and none of Zn or combined Ag, Cu, and Zn surfaces reported cytotoxicity against osteoblasts, stem cells, and immune cells. A majority of the studies investigated the antibacterial activity against S. aureus. Important areas for future research include the biofunctionalization of additively manufactured porous implants and surfaces combining Ag, Cu, and Zn. Furthermore, the antibacterial activity of such implants should be determined in assays focused on prevention, rather than the treatment of IAIs. These implants should be tested using appropriate in vivo bone infection models capable of assessing whether titanium implants biofunctionalized by PEO with Ag, Cu, and Zn can contribute to protect patients against IAI.     

Adhesive Antimicrobial Peptides Containing 3,4-Dihydroxy-L-Phenylalanine Residues for Direct One-Step Surface Coating

Bacterial colonization and transmission via surfaces increase the risk of infection. In this study, we design and employ novel adhesive antimicrobial peptides to prevent bacterial contamination of surfaces. Repeats of 3,4-dihydroxy-L-phenylalanine (DOPA) were added to the C-terminus of NKC, a potent synthetic antimicrobial peptide, and the adhesiveness and antibacterial properties of the resulting peptides are evaluated. The peptide is successfully immobilized on polystyrene, titanium, and polydimethylsiloxane surfaces within 10 min in a one-step coating process with no prior surface functionalization. The antibacterial effectiveness of the NKC-DOPA₅-coated polystyrene, titanium, and polydimethylsiloxane surfaces is confirmed by complete inhibition of the growth of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus within 2 h. The stability of the peptide coated on the substrate surface is maintained for 84 days, as confirmed by its bactericidal activity. Additionally, the NKC-DOPA₅-coated polystyrene, titanium, and polydimethylsiloxane surfaces show no cytotoxicity toward the human keratinocyte cell line HaCaT. The antimicrobial properties of the peptide-coated surfaces are confirmed in a subcutaneous implantation animal model. The adhesive antimicrobial peptide developed in this study exhibits potential as an antimicrobial surface-coating agent for efficiently killing a broad spectrum of bacteria on contact.     

Silicon-Doped Titanium Dioxide Nanotubes Promoted Bone Formation on Titanium Implants

While titanium (Ti) implants have been extensively used in orthopaedic and dental applications, the intrinsic bioinertness of untreated Ti surface usually results in insufficient osseointegration irrespective of the excellent biocompatibility and mechanical properties of it. In this study, we prepared surface modified Ti substrates in which silicon (Si) was doped into the titanium dioxide (TiO₂) nanotubes on Ti surface using plasma immersion ion implantation (PIII) technology. Compared to TiO₂ nanotubes and Ti alone, Si-doped TiO₂ nanotubes significantly enhanced the expression of genes related to osteogenic differentiation, including Col-I, ALP, Runx2, OCN, and OPN, in mouse pre-osteoblastic MC3T3-E1 cells and deposition of mineral matrix. In vivo, the pull-out mechanical tests after two weeks of implantation in rat femur showed that Si-doped TiO₂ nanotubes improved implant fixation strength by 18% and 54% compared to TiO₂-NT and Ti implants, respectively. Together, findings from this study indicate that Si-doped TiO₂ nanotubes promoted the osteogenic differentiation of osteoblastic cells and improved bone-Ti integration. Therefore, they may have considerable potential for the bioactive surface modification of Ti implants.     

Corrosion behavior of Zn-incorporated antibacterial TiO2 porous coating on titanium

Incorporation of antibacterial agents (e.g. Ag and Cu) at the surface of biomedical materials has evolved as a potentially effective method for preventing the bacterial infections. However, the antibacterial efficacy of medical device implants must necessarily be balanced by good corrosion resistance and the corrosion behavior of the antibacterial coatings has seldom been reported. In this work, Zn-incorporated antibacterial TiO₂ coating was produced on pure titanium (Ti) by micro-arc oxidization (MAO) and the electrochemical behavior was assessed. The results obtained from the antibacterial studies suggest that the Zn-incorporated TiO₂ coating provides bactericidal activity against both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) over 90%. The corrosion behavior of Zn-incorporated TiO₂ coating were investigated using a combination of complementary electrochemical measurement techniques such as open circuit potential (OCP), potentiodynamic polarization and electrochemical impedance spectroscopy. The results show that the Zn-incorporated TiO₂ coating move the OCP to the positive direction and increase the polarization resistance, thereby enhances the corrosion resistance of pure Ti. Collectively, the Zn-incorporated TiO₂ coating with both antibacterial ability and anti-corrosive properties might be more suitable for biomedical surfaces.     

Controlling the degradation rate of bioactive magnesium implants by electrophoretic deposition of akermanite coating

In order to improve the corrosion resistance and the surface bioactivity of biodegradable magnesium alloys, a nanostructured akermanite (Ca₂MgSi₂O₇) coating was grown on AZ91 magnesium alloy through electrophoretic deposition (EPD) assisted with micro arc oxidation (MAO) method. The crystalline structures, morphologies and compositions of samples were characterized by X–ray diffraction, scanning electron microscopy and energy dispersive spectroscopy. The in vitro bio–corrosion (biodegradability) and bioactivity behaviors of samples were investigated by electrochemical and immersion tests. The experimental results indicated that the nanostructured akermanite coating could slow down the corrosion rate and improve the in vitro bioactivity of biodegradable magnesium alloy. Thus, magnesium alloy coated with nanostructured akermanite may be a promising candidate to be used as biodegradable bone implants.     

Drug loaded electrospun polymer/ceramic composite nanofibrous coatings on titanium for implant related infections

Developing an effective antibacterial surface with the help of drugs that prevent bacterial adhesion, colonization, and proliferation into the surrounding tissues is of great demand. Rifampicin (Rf) is effective antibiotic drug proved has proved its potential in treating bacteria in biofilms, especially against the microbes causing bone infections. Hydroxyapatite (HA), a biocompatible osteoconductive ceramic, has been verified to be a significant material for bioactivity enhancement. Electrospinning is an effective inexpensive method for incorporating nanoparticles into nanofibers with uniform distribution for the drug delivery system for tissue engineering applications. In the current study, for improving bioactivity and antibacterial properties, novel functional polycaprolactone (PCL) composite nanofibers loaded HA and Rf was developed and coated on titanium (Ti). Different characterization techniques such as SEM, EDS, XRD, FITR were used to analyze these PCL/Rf/HA nanocomposites. The results showed that the bioactivity and tensile strength of the composite scaffold increased with the addition of HA nanoparticles. In vitro bioactivity demonstrated that the PCL/HA/Rf composite nanofibers possess enhanced calcium deposition when compared to the pure sample. Cellular interactive responses such as adhesive and proliferation were evaluated using hFOB human fetal osteoblast cell lines. After 6 days of culturing, the cellular properties on Ti sample coated with PCL/HA/Rf was significantly improved. Antibacterial evaluations on the substrates showed that Rf-loaded PCL/HA fibers displayed >3 log reduction against S.aureus MRSA, and S.epidermidis bacterial strain and >2 log reduction against P.aeruginosa bacteria. In vitro drug release study shows initial burst release of Rf, followed by sustained released of 62% at the end of 32 days. The cell viability, adhesion, and proliferation evaluation suggest that the PCL/HA/Rf coated substrate possess good cytocompatibility. Further incorporation of Rf enhanced the antibacterial property of this nanofibrous scaffold.     

A comprehensive review on biocompatible thin films for biomedical application

Thin films have emerged as an ideal surface treatment to the permanent implant materials to enhance properties such as biodegradation resistance, better mechanical strengths and biocompatibility. A perfect implant ought to have the ability of resistance to degradation, stimulate osseointegration, prevent bacterial adhesion, and decrease prosthetic infection. The clinical success of implants depends on the interaction of cells with material surfaces, which is an essential factor. Recent development in biomaterials has brought a variety of coatings on biomaterial to overcome these issues. The coatings impart biocompatibility, better mechanical property, and bioactivity to the biomaterial. In this review, the recent trends in surface modification by thin films of implants have been discussed in detail.     

Tailoring Additively Manufactured Titanium Implants for Short-Time Pediatric Implantations with Enhanced Bactericidal Activity

Paediatric titanium (Ti) implants are used for the short-term fixation of fractures, after which they are removed. However, bone overgrowth on the implant surface can complicate their removal. The current Ti implants research focuses on improving their osseointegration and antibacterial properties for long-term use while overlooking the requirements of temporary implants. This paper presents the engineering of additively manufactured Ti implants with antibacterial properties and prevention of bone cell overgrowth. 3D-printed implants were fabricated followed by electrochemical anodization to generate vertically aligned titania nanotubes (TNTs) on the surface with specific diameters (∼100 nm) to reduce cell attachment and proliferation. To achieve enhanced antibacterial performance, TNTs were coated with gallium nitrate as antibacterial agent. The physicochemical characteristics of these implants assessed by the attachment, growth and viability of osteoblastic MG-63 cells showed significantly reduced cell attachment and proliferation, confirming the ability of TNTs surface to avoid cell overgrowth. Gallium coated TNTs showed strong antibacterial activity against S. aureus and P. aeruginosa with reduced bacterial attachment and high rates of bacterial death. Thus a new approach for the engineering of temporary Ti implants with enhanced bactericidal properties with reduced bone cell attachment is demonstrated as a new strategy toward a new generation of short-term implants in paediatrics.     

Swelling and electroresponsive characteristics of interpenetrating polymer network hydrogels

Electroactive polymer gels composed of poly(diallyldimethylammonium chloride), poly(acrylic acid) and poly(vinyl alcohol) were prepared and their swelling properties characterized. The swelling behavior of the polymer gels was studied by immersion of the gels into deionized water at room temperature. The state of the water in the polymer gels was characterized using differential scanning calorimetry and the microstructure of the swollen gel in each sample was investigated using scanning electron microscopy. The samples' response to being stimulated in an applied electric field was also investigated. Copyright © 2005 Society of Chemical Industry     

Corrosion behavior of electrochemically assembled nanoporous titania for biomedical applications

Corrosion resistance of nanoporous titania was investigated in Hank’s solution using potentiodynamic polarization and electrochemical impedance spectroscopic techniques. The phase structure, surface morphology and elemental composition of the untreated, anodized heat treated and anodized heat treated titanium specimens immersed in Hank’s solution for seven days were characterized using X-ray diffraction, atomic force microscopy and scanning electron microscopy with energy dispersive X-ray spectroscopy techniques, respectively. The X-ray diffraction technique revealed that the anodized heat treated titanium exhibited anatase structure. The atomic force microscopic and scanning electron microscopic results showed that the titanium surface has transformed from a smooth to nanoporous surface depending on the anodization conditions. The energy dispersive X-ray spectroscopy results confirmed the formation of hydroxyapatite over the anodized titanium after immersion for seven days in Hank’s solution. The electrochemical results revealed that the anodized heat treated titanium after seven day immersion in Hank’s solution showed nobler shift in corrosion potential compared to untreated and anodized titanium. Hence, the results suggested that the nanoporous titania layer developed on titanium is a promising material for application as orthopaedic implants.     

Effects of electrophoretic deposition times and nanotubular oxide surfaces on properties of the nanohydroxyapatite/nanocopper coating on the Ti13Zr13Nb alloy

Load-bearing implants are developed with a particular emphasis placed on an application of ceramic hydroxyapatite coatings in order, to enhance the bioactivity of titanium implants and to shorten the healing time. Therefore, thin, fully crystalline coatings that are, highly adhesive, hydrophilic and demonstrating antibacterial properties are ly looked for. The aim of this research was to develop and characterize the properties of (nano)hydroxyapatite coatings implemented with nanocopper particles and obtained by the electrophoretic method. The deposition was carried out on the Ti13Zr13Nb alloy, either on a bare surface or a nanotubular oxide layer. The deposition was made for 1 or 2 min. The chemical composition, phase composition, coating structure, homogeneity, thickness, nanoindentation and nanomechanical properties, adhesion determined by a nanoscratch test, and wettability measured by a contact angle were investigated. The presence of nanotubular oxide layers caused no significant change in nanoindentation and nanomechanical propertie and an increase in adhesion strength and a decrease in the contact angle. The increase in deposition time resulted in an increased thickness, a decreased hardness, an increased adhesion strength and wettabilty. The observed effects in the composite (nano)HAp/Cu – (nano)TiO₂ coatings are attributed to the change in the structure of coatings following the increasing deposition time and coating thickness.     

Response of osteoblast-like MG63 cells to TiO2 layer prepared by micro-arc oxidation and electric polarization

Micro-arc oxidation (MAO) is one of the useful surface modifications of titanium implants to improve bioactivity. Also, electric polarization treatment enhances bioactivity of calcium phosphate. The aim of this study was to evaluate the effect of the combination of two surface modifications, micro-arc oxidation (MAO) with electric polarization, on the behavior of osteoblast-like osteosarcoma MG63 cells. MAO-treated materials had a surface geometry that was favored by MG63 cells as determined using scanning electron microscopy and X-ray diffraction; additionally, electric polarization induced surface electric fields, which were measured using thermally stimulated depolarization currents. The results of assays to study cell–material interactions suggest that these two approaches could regulate cell attachment, spreading, proliferation, and differentiation without the addition of other reagents. This new surface modification processes produce materials with a good surface geometry, generate surface electric fields and enhance the osteopromotive ability of osteoblasts.     

Strontium and copper co-substituted hydroxyapatite-based coatings with improved antibacterial activity and cytocompatibility fabricated by electrodeposition

Bacterial infection are serious complications for biomedical implants in the orthopedic and dental fields, and the ideal implants should combine good antibacterial ability and bioactivity. In this paper, we have fabricated the strontium/copper substituted hydroxyapatite (SrCuHA) coating on the commercially pure titanium (CP-Ti) and studied their effect on antibacterial and in vitro cytocompatible properties. Cu was incorporated into HA in order to improve its antimicrobial properties. Sr was added as a second binary element to improve the biocompatibility. The structural and morphological characteristics of the SrCuHA coatings were investigated using various analytical techniques. The presence of Sr²⁺ and Cu²⁺ in solution led to reduced roughness of the coating and finer nucleus size formed. The results highlight that Sr²⁺ and Cu²⁺ were homogenously incorporated into HA lattice to form SrCuHA coatings. Inductively coupled plasma mass spectrometry (ICP-MS) was used for the leach out analysis of the samples. A low contact angle value revealed the hydrophilic nature. In vitro electrochemical corrosion studies indicated that the SrCuHA coating sustain in the stimulated body-fluid (SBF), exhibiting superior corrosion resistance with a lower corrosion penetration rate than the bare CP-Ti substrate. The SrCuHA coatings can kill Escherichia coli to a certain extent during the first few days, which might be due to the Cu substitution in the coating. An enhancement of in vitro osteoblast adhesion, proliferation, and alkaline phosphatase activity was observed, which could lead to the optimistic orthopedic and dental applications.     

Comparison of the Osteogenic Potential of Titanium and Modified Zirconia-Based Bioceramics

Zirconia is now favored over titanium for use in dental implant materials because of its superior aesthetic qualities. However, zirconia is susceptible to degradation at lower temperatures. In order to address this issue, we have developed modified zirconia implants that contain tantalum oxide or niobium oxide. Cells attached as efficiently to the zirconia implants as to titanium-based materials, irrespective of surface roughness. Cell proliferation on the polished surface was higher than that on the rough surfaces, but the converse was true for the osteogenic response. Cells on yttrium oxide (Y₂O₃)/tantalum oxide (Ta₂O₅)- and yttrium oxide (Y₂O₃)/niobium oxide (Nb₂O₅)-containing tetragonal zirconia polycrystals (TZP) discs ((Y, Ta)-TZP and (Y, Nb)-TZP, respectively) had a similar proliferative potential as those grown on anodized titanium. The osteogenic potential of MC3T3-E1 pre-osteoblast cells on (Y, Ta)-TZP and (Y, Nb)-TZP was similar to that of cells grown on rough-surface titanium. These data demonstrate that improved zirconia implants, which are resistant to temperature-induced degradation, retain the desirable clinical properties of structural stability and support of an osteogenic response.     

In vitro biocompatibility of a nanocrystalline β-Ta2O5 coating for orthopaedic implants

To improve the durability and bioactivity of Ti–6Al–4V alloy used for medical implants, the β-Ta₂O₅ nano-crystalline coatings were introduced using double cathode glow discharge technique. The coating microstructure was characterized using X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HRTEM). The coating exhibits an assembly of near-equiaxed grains, locally aligned normal to the coating surface. The β-Ta₂O₅ coating exhibits strong adhesion to substrate and a strong resistance to deformation and cracking under applied loads. Cells culture tests showed that the coating is more beneficial to the adhesion and proliferation of NIH-3T3 cells as compared to the uncoated alloy. In-vitro bioactivity was evaluated by immersion of the coating in simulated body fluids (SBF) for different periods up to 14 days at 37 °C. The results indicated that bioactivity of Ti–6Al–4V was dramatically improved after the deposition of β-Ta₂O₅, since the coating has a higher apatite forming ability than the Ti–6Al–4V substrate. Finally, the electrochemical behavior of the β-Ta₂O₅ coating after soaking in SBF at 37 °C for 0, 3, 7, and 14 days was studied through potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). EIS measurements also confirm that the presence of a hydroxyapatite layer on the coating becomes thicker and denser during soaking in SBF. Moreover, the coating exhibits better corrosion resistance than the bare alloy. Hence, the β-Ta₂O₅ coating is a promising candidate coating for protection of orthopedic implants with enhanced bioactivity and corrosion resistance.     

A novel effect of sandblasting on titanium surface: static charge generation

Recent advances in biomaterials’ research suggest that electrical charges on a dental implant surface significantly improve its osseointegration to living bone, as a result of selective osteoblast activation and fibroblast inhibition. This study aims at investigating the possibility of using sandblasting to modify the electrical charges on the surface of titanium materials. Our experiments used Al₂O₃ grits to blast on CP2 titanium plates, for durations between 3 and 30?s. After sandblasting, Ti surfaces were measured for their electrostatic voltage. The results indicate a novel finding, i.e. negative static charges are generated on the titanium surface, which may stimulate osteoblast activity to promote osseointegration around dental implant surface. This finding may at least partially explain the good osseointegration results of sandblasted titanium dental implants, in addition to other known reasons, such as topological changes on the implant’s surface. However, the static charges accumulated on the titanium surface during sandblasting decayed to a lower level with time. It remains a challenging task to seek ways to retain these charges after quantification of desired level of negative charges needed to promote osteoblast activity for osseointegration around dental implants.