Fabrication and evaluation of porous coatings doped with bioactive elements on titanium surfaces.

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.

Phytic Acid-Promoted Deposition of Gold Nanoparticles with Grafted Cationic Polymer Brushes for the Construction of Synergistic Contact-Killing and Photothermal Bactericidal Coatings.

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.

Recent developments in ureteral stent: Substrate material, coating polymer and technology, therapeutic function.

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.

Generalized Multifunctional Coating Strategies Based on Polyphenol-Amine-Inspired Chemistry and Layer-by-Layer Deposition for Blood Contact Catheters.

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.

pH-Responsive antibacterial metal-phenolic network coating on hernia meshes.

Polypropylene (PP) mesh is widely used in hernioplasty, but it is prone to contamination by pathogenic bacteria. Here, we present an infection microenvironment-responsive metal-phenolic network (MPN) coating, which is made up of Cu2+ and tannic acid (TA) (referred to as CT coating), and is fabricated on PP meshes by layer-by-layer (LbL) assembly. The CT coating provided a robust protection for the PP mesh from pathogenic bacterial infection in a pH-responsive manner due to the pH-responsive disassembly kinetics of MPN complexes. Moreover, the PP meshes with ten CT coating cycles (PP-CT(10)) exhibited excellent stability in a physiological environment, with the killing ratio against "superbug" methicillin-resistant Staphylococcus aureus (MRSA) at pH 5.5 exceeding 99% even after 28 days of PBS (pH 7.4) immersion. In addition, the PP-CT(10) exhibited excellent in vivo anti-infective ability in a rodent subcutaneous implant MRSA infection model, and the results of histological and immunohistochemical analyses demonstrated that the reduced bacterial number alleviated the inflammatory response at implant sites. This study revealed that MPN coating is a promising strategy, which could provide a self-defensive ability for various implants to combat post-surgical infections in a pH-responsive manner.

Electrophoretic Deposition of 58S Bioactive Glass- Polymer Composite Coatings on 316L Stainless Steel: An Optimization for Corrosion, Bioactivity, and Cytocompatibility.

This study presents a facile fabrication of 58S bioactive glass (BG)-polymer composite coatings on a 316L stainless steel (SS) substrate using the electrophoretic deposition technique. The suspension characteristics and deposition kinetics of BG, along with three different polymers, namely ethylcellulose (EC), poly(acrylic acid) (PAA), and polyvinylpyrrolidone (PVP), have been utilized to fabricate the coatings. Among all coatings, 58S BG and EC polymers are selected as the final composite coating (EC6) owing to their homogeneity and good adhesion. EC6 coating exhibits a thickness of ∼18 µm and an average roughness of ∼2.5 µm. Herein, EC6 demonstrates better hydroxyapatite formation compared to PAA and PVP coatings in simulated body fluid-based mineralization studies for a period of 28 days. Corrosion studies of EC6 in phosphate-buffered saline further confirm the higher corrosion resistance properties after 14 days. In vitro cytocompatibility studies using human placental mesenchymal stem cells demonstrate an increase in cellular viability, attachment, and higher proliferation compared to the bare SS substrate. EC6 coatings promote osteogenic differentiation, which is confirmed via the upregulation of the OPN and OCN genes. Moreover, the EC6 sample exhibits improved antibacterial properties against Escherichia coli and Staphylococcus aureus compared to the uncoated ones. The findings of this work emphasize the potential of electrophoretically fabricated BG-EC composite coatings on SS substrates for orthopedic applications.

Biocompatibility and Osseointegration of the Biomimetically Coated and Water-Soluble Eggshell Membrane Protein Cross-Linked Ti Alloy Screws.

Background: The surface properties of dental and orthopedic implants are directly related to their osseointegration rate. Coating and/or modifying the implant surface might reduce the time of healing. In this study, we aimed to examine the effects of a hybrid surface consisting of a brushite surface coating and cross-linked water-soluble eggshell membrane protein on the osseointegration of titanium (Ti) screws under in vivo conditions. Methods: Twenty Ti alloy screws were implanted monocortically in anteromedial regions of New Zealand rabbit tibiae. Ten screws were untreated and used as controls. The remaining 10 screws were coated with calcium phosphate and following cross-linked with ostrich eggshell membrane protein. All rabbits were sacrificed six weeks after the surgery. Peri-screw tissues were evaluated by micro-computed tomography (µ-CT), histological and histomorphometrical methods. Results: The µ-CT assessments indicated that the experimental group had significantly higher mean bone surface area (BSA) and trabeculae number (TbN) than those of the control group (p ˂ 0.05). Bone surface area (BV), trabecular separation (TbSp), trabecular thickness (TbTh), and bone mineral density (BMD) scores of the control and experimental groups were quite similar (p > 0.05). The vascularization score of the experimental group was significantly higher than the control group (4.29 vs. 0.92%). No sign of the graft-versus-host reaction was observed. Conclusion: Our findings reveal that coating Ti alloy implants with calcium phosphate cross-linked with ostrich eggshell membrane protein increases the osseointegration of Ti alloy screws by increasing the bone surface area, number of trabeculae and vascularization in the implant site.

A Multifunctional Metal-Phenolic Nanocoating on Bone Implants for Enhanced Osseointegration via Early Immunomodulation.

Surface modification is an important approach to improve osseointegration of the endosseous implants, however it is still desirable to develop a facile yet efficient coating strategy. Herein, a metal-phenolic network (MPN) is proposed as a multifunctional nanocoating on titanium (Ti) implants for enhanced osseointegration through early immunomodulation. With tannic acid (TA) and Sr2+ self-assembled on Ti substrates, the MPN coatings provided a bioactive interface, which can facilitate the initial adhesion and recruitment of bone marrow mesenchymal stem cells (BMSCs) and polarize macrophage toward M2 phenotype. Furthermore, the TA-Sr coatings accelerated the osteogenic differentiation of BMSCs. In vivo evaluations further confirmed the enhanced osseointegration of TA-Sr modified implants via generating a favorable osteoimmune microenvironment. In general, these results suggest that TA-Sr MPN nanocoating is a promising strategy for achieving better and faster osseointegration of bone implants, which can be easily utilized in future clinical applications.

Designer Micro-/Nanocrumpled MXene Multilayer Coatings Accelerate Osteogenesis and Regulate Macrophage Polarization.

Effective tissue regeneration and immune responses are essential for the success of biomaterial implantation. Although the interaction between synthetic materials and biological systems is well-recognized, the role of surface topographical cues in regulating the local osteoimmune microenvironment─specifically, their impact on host tissue and immune cells, and their dynamic interactions─remains underexplored. This study addresses this gap by investigating the impact of surface topography on osteogenesis and immunomodulation. We fabricated MXene/hydroxyapatite (HAP)-coated surfaces with controlled 2.5D nano-, submicro-, and microscale topographical patterns using our custom bottom-up patterning method. These engineered surfaces were employed to assess the behavior of osteoblast precursor cells and macrophage polarization. Our results demonstrate that MXene/HAP-coated surfaces with microscale crumpled topography significantly influence osteogenic activity and macrophage polarization: these surfaces notably enhanced osteoblast precursor cell spreading, proliferation, and differentiation and facilitated a shift in macrophages toward an anti-inflammatory, prohealing M2 phenotype. The observed cell responses indicate that the physical cues from the crumpled topographies, combined with the chemical cues from the MXene/HAP coatings, synergistically create a favorable osteoimmune microenvironment. This study presents the first evidence of employing MXene/HAP-multilayer coated surfaces with finely crumpled topography to concurrently facilitate osteogenesis and immunomodulation for improved implant-to-tissue integration. The tunable topographic patterns of these coatings coupled with a facile and scalable fabrication process make them widely applicable for various biomedical purposes. Our results highlight the potential of these multilayer coatings with controlled topography to improve the in vivo performance and fate of implants by modulating the host response at the material interface.

Self-controllable proteinic antibacterial coating with bacteria-triggered antibiotic release for prevention of periprosthetic infection.

Periprosthetic infection is a devastating postimplantation complication in which a biofilm layer harboring invasive microorganisms forms around orthopedic implants, leading to severe implant failure and patient morbidity. Despite the development of several infection-triggered antibiotic release approaches, most current antibacterial coatings are susceptible to undesired antibiotic leakage or mechanical disintegration during prosthesis installation. Herein, we propose a self-controllable proteinic antibacterial coating capable of both long-lasting adherence onto titanium implant substrates over the implant fixation period and instantaneous bacterial eradication. Importantly, the pH-dependent reversible metal coordination of mussel adhesive protein (MAP) enabled bacterial concentration-dependent antibiotic delivery in response to infection-induced acidification. In addition, the MAP coating exhibited superior self-healable adhesive properties and scratch resistance, which enabled to avert issues associated with mechanical damages, including peeling and cracking, often occurring in conventional implant coating systems. The gentamicin-loaded MAP coating exhibited complete inhibition of bacterial growth in vivo against Staphylococcus aureus penetrations during implantation surgery (immediate infection) and even 4 weeks after implantation (delayed infection). Thus, our antibiotic-loaded MAP hydrogel coating can open new avenues for self-defensive antibiotic prophylaxis to achieve instant and sustainable bacteriocidal activity in orthopedic prostheses. © 2017 Elsevier Inc. All rights reserved.

Colloidal Phenol-Amine Coating on Implants for Improved Anti-Inflammation and Osteogenesis.

Phenol-amine coatings have attracted significant attention in recent years owing to their adjustable composition and multifaceted biological functionalities. The current preparation of phenol-amine coatings, however, involves a chemical reaction within the solution or interface, resulting in lengthy preparation times and necessitating specific reaction conditions, such as alkaline environments and oxygen presence. The facile, rapid, and eco-friendly preparation of phenol-amine coatings under mild conditions continues to pose a challenge. In this study, we use a macromolecular phenol-amine, Tanfloc, to form a stable colloid under neutral conditions, which was then rapidly adsorbed on the titanium surface by electrostatic action and then spread and fused to form a continuous coating within several minutes. This nonchemical preparation process was rapid, mild, and free of chemical additives. The in vitro and in vivo results showed that the Tanfloc colloid fusion coating inhibited destructive inflammation, promoted osteogenesis, and enhanced osteointegration. These remarkable advantages of the colloidal phenol-amine fusion coating highlight the suitability of its future application in clinical practice.

Iodine-doped TiO2 nanotube coatings: a technique for enhancing the antimicrobial properties of titanium surfaces against Staphylococcus aureus.

BACKGROUND: Implant-related infections are a challenging complication of orthopedic surgery, primarily due to the formation of bacterial biofilms on the implant surface. An antibacterial coating for titanium implants was developed to provide novel insights into the prevention and treatment of implant-related infections. METHODS: Titanium plates were coated with TiO2 nanotubes by anodization, and iodine was doped onto the coating via electrophoretic deposition. The obtained plates were characterized using a range of analytical techniques. Subsequently, Staphylococcus aureus was inoculated onto the surfaces of untreated titanium plates (control group), TiO2-nanocoated titanium plates (TiO2 group), and iodine-doped TiO2-nanocoated titanium plates (I-TiO2 group) to compare their antibacterial properties. RESULTS: Twenty-four hour in vitro antimicrobial activity test of the I-TiO2 group against Staphylococcus aureus was superior to those of the other groups, and this difference was statistically significant (P < 0.05). CONCLUSIONS: This coating technology provides a new theoretical basis for the development of anti-infective implants against Staphylococcus aureus in orthopedics.

Electrophoretic deposition of magnesium oxide coating on micro-arc oxidized titanium for antibacterial activity and biocompatibility.

Titanium (Ti) dental implants face risks of early failure due to bacterial adhesion and biofilm formation. It is thus necessary to endow the implant surface with antibacterial ability. In this study, magnesium oxide (MgO) coatings were prepared on Ti by combining micro-arc oxidation (MAO) and electrophoretic deposition (EPD). The MgO nanoparticles homogeneously deposited on the microporous surface of MAO-treated Ti, yielding increasing coverage with the EPD time increased to 15 to 60 s. After co-culture with Porphyromonas gingivalis (P. gingivalis) for 24 h, 48 h, and 72 h, the coatings produced antibacterial rates of 4-53 %, 27-71 %, and 39-79 %, respectively, in a dose-dependent manner. Overall, EPD for 45 s offered satisfactory comprehensive performance, with an antibacterial rate 79 % at 72 h and a relative cell viability 85 % at 5 d. Electron and fluorescence microscopies revealed that, both the density of adherent bacterial adhesion on the surface and the proportion of viable bacteria decreased with the EPD time. The morphology of cells on the surface of each group was intact and there was no significant difference among the groups. These results show that, the MgO coating deposited on MAO-treated Ti by EPD had reasonably good in vitro antibacterial properties and cytocompatibility.

Engineering Immunomodulatory Stents Using Zinc Ion-Lysozyme Nanoparticle Platform for Vascular Remodeling.

Rapid endothelialization of cardiovascular materials can enhance the vascular remodeling performance. In this work, we developed a strategy for amyloid-like protein-assembly-mediated interfacial engineering to functionalize a biomimetic nanoparticle coating (BMC). Various groups (e.g., hydroxyl and carboxyl) on the BMC are responsible for chelating Zn2+ ions at the stent interface, similar to the glutathione peroxidase-like enzymes found in vivo. This design could reproduce the release of therapeutic nitric oxide gas (NO) and an aligned microenvironment nearly identical with that of natural vessels. In a rabbit abdominal aorta model, BMC-coated stents promoted vascular healing through rapid endothelialization and the inhibition of intimal hyperplasia in the placement sites at 4, 12, and 24 weeks. Additionally, better anticoagulant activity and immunomodulation in the BMC stents were also confirmed, and vascular healing was mainly dependent on cell signaling through the cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) cascade. Overall, a metal-polypeptide-coated stent was developed on the basis of its detailed molecular mechanism of action in vascular remodeling.

Layer-by-Layer Deposition of Regenerated Silk Fibroin─An Approach to the Surface Coating of Biomedical Implant Materials.

Biomaterials and coating techniques unlock major benefits for advanced medical therapies. Here, we explored layer-by-layer (LbL) deposition of silk fibroin (SF) by dip coating to deploy homogeneous films on different materials (titanium, magnesium, and polymers) frequently used for orthopedic and other bone-related implants. Titanium and magnesium specimens underwent preceding plasma electrolytic oxidation (PEO) to increase hydrophilicity. This was determined as surface properties were visualized by scanning electron microscopy and contact angle measurements as well as Fourier transform infrared spectroscopy (FTIR) analysis. Finally, biological in vitro evaluations of hemocompatibility, THP-1 cell culture, and TNF-α assays were conducted. A more hydrophilic surface could be achieved using the PEO surface, and the contact angle for magnesium and titanium showed a reduction from 73 to 18° and from 58 to 17°, respectively. Coating with SF proved successful on all three surfaces, and coating thicknesses of up to 5.14 µm (±SD 0.22 µm) were achieved. Using FTIR analysis, it was shown that the insolubility of the material was achieved by post-treatment with water vapor annealing, although the random coil peak (1640-1649 cm-1) and the α-helix peak (at 1650 cm-1) were still evident. SF did not change hemocompatibility, regardless of the substrate, whereas the PEO-coated materials showed improved hemocompatibility. THP-1 cell culture showed that cells adhered excellently to all of the tested material surfaces. Interestingly, SF coatings induced a significantly higher amount of TNF-α for all materials, indicating an inflammatory response, which plays an important role in a variety of physiological processes, including osteogenesis. LbL coatings of SF are shown to be promising candidates to modulate the body's immune response to implants manufactured from titanium, magnesium, and polymers. They may therefore facilitate future applications for bioactive implant coatings. However, further in vivo studies are needed to confirm the proposed effects on osteogenesis in a physiological environment.

A nitric oxide-catalytically generating carboxymethyl chitosan/sodium alginate hydrogel coating mimicking endothelium function for improving the biocompatibility.

Thanks to their outstanding mechanical properties and corrosion resistance in physiological environments, titanium and its alloys are broadly explored in the field of intravascular devices. However, the biocompatibility is insufficient, causing thrombus formation and even implantation failure. In this study, inspired by the functions of endothelial glycocalyx and the NO-releasing of endothelial cells (ECs), a biomimetic coating (TNTA-Se) with three-dimensional gel-like structures and NO-catalytically generating ability was constructed on the titanium surface. To this end, the titanium alloy was firstly anodized and then annealed to form nanotube structures imitating the three-dimensional villous of glycocalyx, followed by the preparation of the Cu2+-loaded polydopamine intermediate layer for the immobilization of carboxymethyl chitosan and sodium alginate to form the hydrogel structure. Finally, an organoselenium compound (selenocystamine) as an active catalyst was covalently immobilized on the surface to develop a bioactive coating mimicking endothelial function with NO-generating activity. The surface morphologies and chemical structures of the biomimetic coating were characterized by scanning electron microscopy (SEM), energy dispersion X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and the results indicated that the NO-catalytically generating hydrogel coating was successfully constructed. The results of water contact angle and protein adsorption suggested that the TNTA-Se coating exhibited excellent hydrophilicity, the promotion of bovine serum albumin (BSA) adsorption while the inhibition of fibrinogen (FIB) adsorption. Upon the addition of NO donor S-nitroso glutathione (GSNO) and reducing agent glutathione (GSH), the surface (TNTA-NO) displayed excellent blood compatibility and cytocompatibility to ECs. Compared with other surfaces, the TNTA-NO coating can not only further promote BSA adsorption and inhibit the adhesion and activation of platelets as well as hemolysis, but also significantly enhance ECs adhesion and proliferation and up-regulate VEGF and NO expression of ECs. The current study demonstrated that the NO-catalytically generating hydrogel coating on the titanium alloy can mimic the glycocalyx structure and endothelium function to catalyze a large number of NO donors in human blood to produce NO, and thus simultaneously enhance the surface hemocompatibility and endothelialization, representing a promising strategy for long-term cardiovascular implants of titanium-based devices.

Reduced Cell Adhesion on LightPLAS-Coated Implant Surfaces in a Three-Dimensional Bioreactor System.

Most implants used in trauma surgery are made of steel and remain inside the body only temporarily. The strong tissue interaction of such implants sometimes creates problems with their explantation. Modified implant surfaces, which decrease tissue attachment, might allow an easier removal and therefore a better outcome. Such a modification must retain the implant function, and needs to be biocompatible and cost-effective. Here, we used a novel VUV-light (Vacuum-Ultraviolett)-based coating technology (LightPLAS) to generate coated stainless-steel plates. The tested LightPLAS coating only had an average thickness of around 335 nm, making it unlikely to interfere with implant function. The coated plates showed good biocompatibility according to ISO 10993-5 and ISO 10993-12, and reduced cell adhesion after four different time points in a 2D cell culture system with osteoblast-like MG-63 cells. Furthermore, we could show decreased cell adhesion in our 3D cell culture system, which mimics the fluid flow above the implant materials as commonly present in the in vivo environment. This new method of surface coating could offer extended options to design implant surfaces for trauma surgery to reduce cell adhesion and implant ingrowth. This may allow for a faster removal time, resulting in shorter overall operation times, thereby reducing costs and complication rates and increasing patient wellbeing.

Osteoconductive, Osteogenic, and Antipathogenic Plasma Electrolytic Oxidation Coatings on Titanium Implants with BMP-2.

We report a one-pot plasma electrolytic oxidation (PEO) strategy for forming a multi-element oxide layer on the titanium surface using complex electrolytes containing Na2HPO4, Ca(OH)2, (NH2)2CO, Na2SiO3, CuSO4, and KOH compounds. For even better bone implant ingrowth, PEO coatings were additionally loaded with bone morphogenetic protein-2 (BMP-2). The samples were tested in vivo in a mouse craniotomy model. Tests for bactericidal and fungicidal activity were carried out using clinically isolated multi-drug-resistant Escherichia coli (E. coli) K261, E. coli U20, methicillin-resistant Staphylococcus aureus (S. aureus) CSA154 bacterial strains, and Neurospora crassa (N. crassa) and Candida albicans (C. albicans) D2528/20 fungi. The PEO-Cu coating effectively inactivated both Gram-positive and Gram-negative bacteria at low concentrations of Cu2+ ions: minimal bactericidal concentration for E. coli and N. crassa (99.9999%) and minimal inhibitory concentration (99.0%) for S. aureus were 5 ppm. For all studied bacterial and fungal strains, PEO-Cu coating completely prevented the formation of bacterial and fungal biofilms. PEO and PEO-Cu coatings demonstrated bone remodeling and moderate osteoconductivity in vivo, while BMP-2 significantly enhanced osteoconduction and osteogenesis. The obtained results are encouraging and indicate that Ti-based materials with PEO coatings loaded with BMP-2 can be widely used in customized medicine as implants for orthopedics and cranio-maxillofacial surgery.

Antimicrobial efficacy of cyclic α- and ß-peptides incorporated in polyurethane coatings.

Microbial growth on surfaces poses health concerns and can accelerate the biodegradation of engineered materials and coatings. Cyclic peptides are promising agents to combat biofouling because they are more resistant to enzymatic degradation than their linear counterparts. They can also be designed to interact with extracellular targets and intracellular targets and/or self-assemble into transmembrane pores. Here, we determine the antimicrobial efficacy of two pore-forming cyclic peptides, α-K3W3 and ß-K3W3, against bacterial and fungal liquid cultures and their capacity to inhibit biofilm formation on coated surfaces. These peptides display identical sequences, but the additional methylene group in the peptide backbone of ß-amino acids results in a larger diameter and an enhancement in the dipole moment. In liquid cultures, ß-K3W3 exhibited lower minimum inhibitory concentration values and greater microbicidal power in reducing the number of colony forming units (CFUs) when exposed to a gram-positive bacterium, Staphylococcus aureus, and two fungal strains, Naganishia albida and Papiliotrema laurentii. To evaluate the efficacy against the formation of fungal biofilms on painted surfaces, cyclic peptides were incorporated into polyester-based thermoplastic polyurethane. The formation of N. albida and P. laurentii microcolonies (105 per inoculation) for cells extracted from coatings containing either peptide could not be detected after a 7-day exposure. Moreover, very few CFUs (∼5) formed after 35 days of repeated depositions of freshly cultured P. laurentii every 7 days. In contrast, the number of CFUs for cells extracted from the coating without cyclic peptides was >8 log CFU.

Smart Implant with Bacteria Monitoring and Killing Ability for Orthopedic Applications.

Bacterial infections around implants constitute a significant cause of implant failures. Early recognition of bacterial adhesion is an essential factor in preventing implant infections. Therefore, an implant capable of detecting and disinfecting initial bacterial adhesion is required. This study reports on the development of an intelligent solution for this issue. We developed an implant integrated with a biosensor electrode based on alternating current (AC) impedance technology to monitor the early growth process of Escherichia coli (E. coli) and its elimination. The biosensor electrode was fabricated by coating polypyrrole (PPy) doped with sodium p-toluenesulfonate (TSONa) on titanium (Ti) surfaces. Monitoring the change in resistance using electrochemical impedance spectroscopy (EIS), combined with an equivalent circuit model (ECM), enables the monitoring of the early adhesion of E. coli. The correlation with the classical optical density (OD) monitoring value reached 0.989. Subsequently, the eradication of bacteria on the electrode surface was achieved by applying different voltages to E. coli cultured on the electrode surface, which caused damage to E. coli. Furthermore, in vitro cellular experiments showed that the PPy coating has good biocompatibility and can promote bone differentiation.