Recent Advances in Metal-Based Antimicrobial Coatings for High-Touch Surfaces.

International interest in metal-based antimicrobial coatings to control the spread of bacteria, fungi, and viruses via high contact human touch surfaces are growing at an exponential rate. This interest recently reached an all-time high with the outbreak of the deadly COVID-19 disease, which has already claimed the lives of more than 5 million people worldwide. This global pandemic has highlighted the major role that antimicrobial coatings can play in controlling the spread of deadly viruses such as SARS-CoV-2 and scientists and engineers are now working harder than ever to develop the next generation of antimicrobial materials. This article begins with a review of three discrete microorganism-killing phenomena of contact-killing surfaces, nanoprotrusions, and superhydrophobic surfaces. The antimicrobial properties of metals such as copper (Cu), silver (Ag), and zinc (Zn) are reviewed along with the effects of combining them with titanium dioxide (TiO2) to create a binary or ternary contact-killing surface coatings. The self-cleaning and bacterial resistance of purely structural superhydrophobic surfaces and the potential of physical surface nanoprotrusions to damage microbial cells are then considered. The article then gives a detailed discussion on recent advances in attempting to combine these individual phenomena to create super-antimicrobial metal-based coatings with binary or ternary killing potential against a broad range of microorganisms, including SARS-CoV-2, for high-touch surface applications such as hand rails, door plates, and water fittings on public transport and in healthcare, care home and leisure settings as well as personal protective equipment commonly used in hospitals and in the current COVID-19 pandemic.

Coating gold nanorods with silica prevents the generation of reactive oxygen species under laser light irradiation for safe biomedical applications.

Gold nanoparticles can produce reactive oxygen species (ROS) under the action of ultrashort pulsed light. While beneficial for photodynamic therapy, this phenomenon is prohibitive for other biomedical applications such as imaging, photo-thermal drug release, or targeted gene delivery. Here, ROS are produced in water by irradiating gold nanorods and silica-coated gold nanorods with near-infrared femtosecond laser pulses and are detected using two fluorescent probes. Our results demonstrate that a dense silica shell around gold nanorods inhibits the formation of singlet oxygen (1O2) and hydroxyl radical (˙OH) efficiently. The silica coating prevents the Dexter energy transfer between the nanoparticles and 3O2, stopping thus the generation of 1O2. In addition, numerical simulations accounting for the use of ultrashort laser pulses show that the plasmonic field enhancement at the nanoparticle vicinity is lessened once adding the silica layer. With the multiphotonic ejection of electrons being also blocked, all the possible pathways for ROS production are hindered by adding the silica shell around gold nanorods, making them safer for a range of biomedical developments.

Stability and surface properties of selenium nanoparticles coated with chitosan and sodium carboxymethyl cellulose.

The effect of polysaccharide coatings on the stability and release characteristics of selenium nanoparticles (SeNPs) was evaluated by comparing the characteristics of chitosan-coated SeNPs (CS-SeNPs) and sodium carboxymethyl cellulose-coated SeNPs (CMC-SeNPs). The release characteristics of SeNPs were investigated in storage conditions, gastrointestinal conditions, and free radical systems. CMC-SeNPs formed dimers or trimers, whereas CS-SeNPs were monodispersed but formed large aggregates in a pH range of 7.4-8.25. Upon 50 days of storage at 30 °C, both CMC-SeNPs and CS-SeNPs were converted to Se4+. SeNPs exhibited a lower release rate in simulated gastrointestinal conditions than in free radical systems. SeNPs release in ABTS and superoxide anion free radical systems followed the first-order and Korsmeyer-Peppas models, respectively, indicating that SeNP release is mainly governed by dissolution mechanisms. Additional studies are needed to examine the potential environmental effects and biological activity of the Se4+ released from SeNPs.

High-Efficient Vacuum Ultraviolet-Ozone Assist-Deposited Polydopamine for Poly(lactic-co-glycolic acid)-Coated Pure Zn toward Biodegradable Cardiovascular Stent Applications.

Zinc is a prospective metal for biodegradable cardiovascular stent applications, but the excessively released Zn2+ during degradation remains a huge challenge in biocompatibility. Considerable efforts have been made to develop a high-efficient surface modification method, while maintaining adhesion strength, mechanical support, and vascular compatibility. Biomimetic polydopamine (PDA) can adhere to Zn tightly, subsequently achieving robust chemical bonds with poly(lactic-co-glycolic acid) (PLGA) coating. However, the deposition of PDA on Zn depends on the controlled conditions such as a sensitive pH and a long period of time. Herein, we introduce vacuum ultraviolet-ozone (VUV/O3) assist-deposition technology to accelerate the polymerization of PDA on pure Zn, which shortens the process to 40 min at a moderate pH of 8.5 and improves the deposition rate by 1-2 orders of magnitude under sufficient active oxygen species (ROS). Additionally, PLGA/PDA coating enhances the corrosion resistance, and their effective protection maintains the mechanical properties after long-term corrosion. Moreover, the controlled Zn2+ release contributes to the superior in vitro biocompatibility, which inhibits the hemolysis rate and smooth muscle cell (SMC) proliferation. The enhanced endothelial cell (EC) proliferation is promising to promote the re-endothelialization, avoiding in-stent restenosis and neointimal hyperplasia. Such modified Zn might be a viable candidate for the treatment of cardiovascular diseases.

Chemically Engineered Porous Molecular Coatings as Reactive Oxygen Species Generators and Reservoirs for Long-Lasting Self-Cleaning Textiles.

Wearable personal protective equipment that is decorated with photoactive self-cleaning materials capable of actively neutralizing biological pathogens is in high demand. Here, we developed a series of solution-processable, crystalline porous materials capable of addressing this challenge. Textiles coated with these materials exhibit a broad range of functionalities, including spontaneous reactive oxygen species (ROS) generation upon absorption of daylight, and long-term ROS storage in dark conditions. The ROS generation and storage abilities of these materials can be further improved through chemical engineering of the precursors without altering the three-dimensional assembled superstructures. In comparison with traditional TiO2 or C3 N4 self-cleaning materials, the fluorinated molecular coating material HOF-101-F shows a 10- to 60-fold enhancement of ROS generation and 10- to 20-fold greater ROS storage ability. Our results pave the way for further developing self-cleaning textile coatings for the rapid deactivation of highly infectious pathogenic bacteria under both daylight and light-free conditions.

Bioactive glasses incorporating less-common ions to improve biological and physical properties.

Bioactive glasses (BGs) have been a focus of research for over five decades for several biomedical applications. Although their use in bone substitution and bone tissue regeneration has gained important attention, recent developments have also seen the expansion of BG applications to the field of soft tissue engineering. Hard and soft tissue repair therapies can benefit from the biological activity of metallic ions released from BGs. These metallic ions are incorporated in the BG network not only for their biological therapeutic effects but also in many cases for influencing the structure and processability of the glass and to impart extra functional properties. The "classical" elements in silicate BG compositions are silicon (Si), phosphorous (P), calcium (Ca), sodium (Na), and potassium (K). In addition, other well-recognized biologically active ions have been incorporated in BGs to provide osteogenic, angiogenic, anti-inflammatory, and antibacterial effects such as zinc (Zn), magnesium (Mg), silver (Ag), strontium (Sr), gallium (Ga), fluorine (F), iron (Fe), cobalt (Co), boron (B), lithium (Li), titanium (Ti), and copper (Cu). More recently, rare earth and other elements considered less common or, some of them, even "exotic" for biomedical applications, have found room as doping elements in BGs to enhance their biological and physical properties. For example, barium (Ba), bismuth (Bi), chlorine (Cl), chromium (Cr), dysprosium (Dy), europium (Eu), gadolinium (Gd), ytterbium (Yb), thulium (Tm), germanium (Ge), gold (Au), holmium (Ho), iodine (I), lanthanum (La), manganese (Mn), molybdenum (Mo), nickel (Ni), niobium (Nb), nitrogen (N), palladium (Pd), rubidium (Rb), samarium (Sm), selenium (Se), tantalum (Ta), tellurium (Te), terbium (Tb), erbium (Er), tin (Sn), tungsten (W), vanadium (V), yttrium (Y) as well as zirconium (Zr) have been included in BGs. These ions have been found to be particularly interesting for enhancing the biological performance of doped BGs in novel compositions for tissue repair (both hard and soft tissue) and for providing, in some cases, extra functionalities to the BG, for example fluorescence, luminescence, radiation shielding, anti-inflammatory, and antibacterial properties. This review summarizes the influence of incorporating such less-common elements in BGs with focus on tissue engineering applications, usually exploiting the bioactivity of the BG in combination with other functional properties imparted by the presence of the added elements.

Enhanced model protein adsorption of nanoparticulate hydroxyapatite thin films on silk sericin and fibroin surfaces.

Hydroxyapatite coated metallic implants favorably combine the required biocompatibility with the mechanical properties. As an alternative to the industrial coating method of plasma spraying with inherently potential deleterious effects, sol-gel methods have attracted much attention. In this study, the effects of intermediate silk fibroin and silk sericin layers on the protein adsorption capacity of hydroxyapatite films formed by a particulate sol-gel method were determined experimentally. The preparation of the layered silk protein/hydroxyapatite structures on glass substrates, and the effects of the underlying silk proteins on the topography of the hydroxyapatite coatings were described. The topography of the hydroxyapatite layer fabricated on the silk sericin was such that the hydroxyapatite particles were oriented forming an oriented crystalline surface. The model protein (bovine serum albumin) adsorption increased to 2.62 µg/cm2 on the latter surface as compared to 1.37 µg/cm2 of hydroxyapatite on glass without an intermediate silk sericin layer. The BSA adsorption on glass (blank), glass/c-HAp, glass/m-HAp, glass/sericin/c-HAp, and glass/sericin/m-HAp substrates, reported as decrease in BSA concentration versus contact time.

Design of a Smart Self-Healing Coating with Multiple-Responsive Superhydrophobicity and Its Application in Antibiofouling and Antibacterial Abilities.

Inspired by the restoration of the superhydrophobic surfaces after the damage in nature such as lotus leaf and clover, smart self-healing coating with controllable release of loaded healing agents is both of scientific and technological interest. Herein, a smart self-healing coating with superhydrophobicity was gained through blending UV/NIR/acid/base multiple-responsive ZnO-encapsulated mesoporous polydopamine (MPDA) microspheres (zinc oxide-encapsulated mesoporous polydopamine microspheres) with silicone latex and hydrophobic nanoparticles. The hydrophobic and micro/nanostructured ZnO-encapsulated MPDA microspheres provided UV/NIR/acid/base multiple response sources for the smart self-healing coating, combining the photocatalytic activity and acid/base solubility of ZnO nanoparticles, zwitterionic characteristic of amino-modified silicone oil (ASO), as well as the photothermal conversion abilities and charge characteristics of PDA. The ZnO nanoparticles simultaneously acted as the protective layer for the stimuli-responsive microspheres and functional filler in the coating, contributing to realize the controllable and long-period release of loaded hydrophobic ASO and the further antibacterial functionalization for the coating. The super/high hydrophobicity and antibiofouling performances of the coating could be self-healed by UV, NIR, acid, or base stimuli, attributing to the release of ASO from the microspheres. Then, large-area, rapid, and controllable healing superiority could be achieved on the coating with the combined multiple responses under different conditions. Robust environmental endurances for superhydrophobic coating were also confirmed under harsh environments by directly exposing to UV-accelerated weathering and immersing into various solutions (including strong acid/base, salt, and artificial seawater solution). This smart coating has high application prospects due to its environmentally friendly nature, excellent self-healing, and multifunctional characteristics, and the multiple-responsive ZnO-encapsulated MPDA microspheres can be used for the functionalization of other materials.

Effect of Nanoparticle Synthetic Conditions on Ligand Coating Integrity and Subsequent Nano-Biointeractions.

Most current nanoparticle formulations have relatively low clearance efficiency, which may hamper their likelihood for clinical translation. Herein, we sought to compare the clearance and cellular distribution profiles between sub-5 nm, renally-excretable silver sulfide nanoparticles (Ag2S-NPs) synthesized via either a bulk, high temperature, or a microfluidic, room temperature approach. We found that the thermolysis approach led to significant ligand degradation, but the surface coating shell was unaffected by the microfluidic synthesis. We demonstrated that the clearance was improved for Ag2S-NPs with intact ligands, with less uptake in the liver. Moreover, differential distribution in hepatic cells was observed, where Ag2S-NPs with degraded coatings tend to accumulate in Kupffer cells and those with intact coatings are more frequently found in hepatocytes. Therefore, understanding the impact of synthetic processes on ligand integrity and subsequent nano-biointeractions will aid in designing nanoparticle platforms with enhanced clearance and desired distribution profiles.

Heparin-Coated Photosensitive Metal-Organic Frameworks as Drug Delivery Nanoplatforms of Autophagy Inhibitors for Sensitized Photodynamic Therapy against Breast Cancer.

Photosensitive nanosized metal-organic frameworks (nanoMOFs) with a tunable structure and high porosity have been developed recently as nanophotosensitizers (nanoPSs) for photodynamic therapy (PDT). However, the effect of photodynamic therapy is greatly limited by the fast blood clearance and poor tumor retention of the ordinary nanoPSs. Besides, autophagy, a prosurvival self-cannibalization pathway mediated by autolysosomes, was elevated by cytotoxic reactive oxygen species (ROS) produced during PDT. Herein, a chloroquine phosphate (CQ)-loaded photosensitive nanoMOF coated by heparin was fabricated for sensitized PDT by increasing the tumor accumulation of nanoPSs and abolishing the self-protective autophagy within cancer cells. After internalization by cancer cells, the encapsulated CQ alkalizes autolysosomes and blocks the postautophagy process, which disarm the vigilant cancer cells irritated by PDT and finally enhance the therapeutic effect. Furthermore, the accompanied antiangiogenesis ability of the heparin coat also helps improve the cancer therapy outcomes. This study would open up new horizons for building heparin-coated nanoMOFs and understanding the role of autophagy in cancer therapy.

Stable Loading and Delivery of Melittin with Lipid-Coated Polymeric Nanoparticles for Effective Tumor Therapy with Negligible Systemic Toxicity.

Melittin is a potential anticancer candidate with remarkable antitumor activity and ability to overcome tumor drug resistance. However, the clinical applications of melittin are largely restricted by its severe hemolytic activity and nonspecific cytotoxicity after systemic administration. Here, a biocompatible and stable melittin-loaded lipid-coated polymeric nanoparticle (MpG@LPN) formulation that contains a melittin/poly-γ-glutamic acid nanoparticle inner core, a lipid membrane middle layer, and a polyethylene glycol (PEG) and PEG-targeting molecule outer shell was designed. The formulations were prepared by applying a self-assembly procedure based on intermolecular interactions, including electrostatic attraction and hydrophobic effect. The core-shell MpG@LPN presented high efficiency for melittin encapsulation and high stability in physiological conditions. Hemolysis and cell proliferation assays showed that the PEG-modified MpG@LPN had almost no hemolytic activity and nonspecific cytotoxicity even at high concentrations. The modification of targeting molecules on the MpG@LPNs allowed for the selective binding with target tumor cells and cytolytic activity via apoptosis induction. In vivo experiments revealed that MpG@LPNs can remarkably inhibit the growth of tumors without the occurrence of hemolysis and tissue toxicity. Results suggested that the developed MpG@LPN with a core-shell structure can effectively address the main obstacles of melittin in clinical applications and has great potential in cancer treatment.

Poly(vinyl alcohol)/phosphoric acid gel electrolyte@polydimethylsiloxane sponge for piezoresistive pressure sensors.

Piezoresistive pressure sensors based on flexible, ultrasensitive, and squeezable conductive sponges have recently attracted significant attention. However, the preparation of cost-effective conductive sponges with good stability and wide strain range for pressure sensing remains a challenge. Herein, a conductive poly(vinyl alcohol)/phosphoric acid gel electrolyte@polydimethylsiloxane (PVA/H3PO4@PDMS) composite was fabricated by impregnating a PDMS sponge into a PVA/H3PO4 gel electrolyte. The conductivity of the as-prepared sponges was determined using a gel electrolyte polymer film. The sponge exhibited good sensitivity of 0.1145 kPa-1 in the low-pressure range (0-6.5 kPa), short response time (70 ms), and durability for over 2700 s (6000 cycles). The gauge factor of the PVA/H3PO4@PDMS sponge was 5.51, 1.49, and 0.33 at the strain range of 0-10%, 10-30%, and 30-80%, respectively. Based on these outstanding sensing performances, the sponges were applied for the detection of various human motions, such as vocal cord vibration, joint bending, respiratory rate, and pulse signal detection. Further, the sponge demonstrated their great potential in the fabrication of electronic skin and high-performance flexible wearable electronics. Therefore, the obtained PVA/H3PO4 gel electrolyte used as a sponge conductive coating material is a readily available and inexpensive material that can reduce the cost of composite materials for pressure sensing.

General Thermodynamic-Controlled Coating Method to Prepare Janus Mesoporous Nanomotors for Improving Tumor Penetration.

Artificial nanomotors are undergoing significant developments in several biomedical applications. However, current experimental strategies for producing nanomotors still have inherent drawbacks such as the requirement for expensive equipment, strict controlling of experimental conditions, and strenuous processes with several complex procedures. In this study, we describe for the first time a facile single-step thermodynamic-controlled coating method to prepare Janus mesoporous organosilica nanomotors. By controlling the total free energy of organosilica oligomers (G) from a low development level to a high level in the reaction system, the nonspontaneous nucleation on the platinum (Pt) nanosurface and the spontaneous nucleation in a solvent can be controlled, respectively. More importantly, we reveal that the molecular arrangement and contact angle of deposited organosilica on Pt cores vary with the total free energy of organosilica oligomers (G). Different values of θ would change the trend of detachment from Pt for organosilica nucleated cores and carry out diverse coating modes. These are indicated by the morphology evolution of platinum/organosilica hybrids, from naked platinum nanoparticles, evenly distributed organosilica shell/core, nonconcentric to typical Janus nanomotor. The prepared Janus mesoporous nanomotor (JMN) showed typical mesopore structures and active propelling behaviors under H2O2 stimulation. In addition, the JMN modified with hyaluronic acid exhibited excellent biocompatibility and improved tumor penetration under H2O2 stimulation. The successful construction of other nanomotor frameworks based on a gold-templated core proves the perfect applicability of the thermodynamic-coating method for the production of nanomotors. In conclusion, this work establishes a manufacturing methodology for nanomotors and drives nanomotors for promising biomedical applications.

Calcium hydroxyapatite nanoparticles as a reinforcement filler in dental resin nanocomposite.

The current study focuses on the fabrication of calcium hydroxyapatite (Ca10(PO4)6(OH)2) (HA) in a nanorange having whiskers- and cubic-shaped uniform particle morphology. The synthesized HA particles hold a promising feature as reinforcement fillers in dental acrylic resin composite. They increase the efficacy of reinforcement by length and aspect ratio, uniformity, and monodispersity. Therefore, the acrylic resin was reinforced with the as-synthesized monodispersed HA filler particles (0.2-1 Wt%). The presence of filler particles in the composite had a noticeable effect on the tribological and mechanical properties of the dental material. The morphological effect of HA particles on these properties was also investigated, revealing that cubic-shaped particles showed better results than whiskers. The as-fabricated composite (0.4 Wt%) of the cubic-shaped filler particles showed maximum hardness and improved antiwear/antifriction properties. Particle loading played its part in determining the optimum condition, whereas particle size also influenced the reinforcement efficiency. The current study revealed that particle morphology, particle size, uniformity, etc., of HA fillers, greatly influenced the tribological and mechanical properties of the acrylic resin-based nanocomposite. Improvement in the tribological properties of HA particle-reinforced acrylic resin composites (HA-acrylic resin) followed the trend as AR < CmC < WC < CC.

Evaluation of Ti/Al alloy coated with biogenic hydroxyapatite as an implant device in dogs' femur bones.

The main target of the present research was a full assessment of the toxicity effects and biocompatibility of a Ti/Al-alloy device coated with biogenic hydroxyapatite (bHA) when implanted in dogs in comparison with those of an uncoated Ti/Al-alloy device. The coating of the alloy was carried out using controlled high-velocity suspension flame spray (HVSFS) technique. Both coated and uncoated devices were implanted in dogs' femur bones for different time periods (45 days and 90 days). Bone-formation ability and healing were followed up, and blood analysis was performed, at Time zero (immediately post surgery), and then at 3 days, 45 days, and 90 days post surgery. Bone mineral density checks, radiological scans of the femur bone, and histological analysis were also conducted. The in-vivo study results proved that implantation of a device made from bHA-coated Ti/Al alloy in dogs' femur bones is completely safe. This is due to the high osteoconductivity of the coated alloy, which enables the formation of new bone and a full connection between new and original bone material. At 90 days post surgery, the coated alloy had been completely digested within the original bone; thus, it appeared as a part of the femur bone and not as a foreign body. Both the scanning electron microscopy with energy-dispersive X-ray and histology analysis findings affirmed the results. Furthermore, the blood tests indicated no toxicity effects during the 90 days of implantation.

Nanocomposite coating of albumin/Li-containing bioactive glass nanospheres promotes osteogenic activity of PEEK.

Polyetheretherketone (PEEK) is an important material applied in orthopedic applications, as it posses favorable properties for orthopedic implants, e.g., radiolucency and suitable elastic modulus. However, PEEK exhibits insufficient osteogenesis and osteointegration that limits its clinical applications. In this study, we aimed to enhance the osteogenisis of PEEK by using a surface coating approach. Nanocomposite coating composed of albumin/lithium containing bioactive glass nanospheres was fabricated on PEEK through dip-coating method. The presence of nanocomposite coating on PEEK was confirmed by SEM, FTIR, and XRD techniques. Nanocomposite coatings significantly enhanced hydrophilicity and roughness of PEEK. The nanocomposite coatings also enhanced adhesion, proliferation, and osteogenic differentiation of bone mesenchymal stem cells due to the presence of bioactive glass nanospheres and the BSA substrate film. The results indicate the great potential of the nanocomposite coating in enhancing osteogenesis and osteointegration of PEEK implants.

Synthesis of silver nanoparticle-decorated hydroxyapatite nanocomposite with combined bioactivity and antibacterial properties.

Combination of bioactive material such as hydroxyapatite (HAp) with antibacterial agents would have great potential to be used as bone implant materials to avert possible bacterial infection that can lead to implant-associated diseases. The present study aimed to develop an antibacterial silver nanoparticle-decorated hydroxyapatite (HAp/AgNPs) nanocomposite using chemical reduction and thermal calcination approaches. In this work, natural HAp that was extracted from chicken bone wastes is used as support matrix for the deposition of silver nanoparticles (AgNPs) to produce HAp/AgNPs nanocomposite. XRD, FESEM-EDX, HRTEM, and XPS analyses confirmed that spherical AgNPs were successfully synthesized and deposited on the surface of HAp particles, and the amount of AgNPs adhered on the HAp surface increased with increasing AgNO3 concentration used. The synthesized HAp/AgNPs nanocomposites demonstrated strong antibacterial activity against Staphylococcus aureus bacteria, where the antibacterial efficiency is relied on the amount and size of deposited AgNPs. In addition, the in vitro bioactivity examination in Hank's balanced salt solution showed that more apatite were grown on the surface of HAp/AgNPs nanocomposite when AgNO3 concentration used >1 wt.%. Such nanocomposite with enhanced bioactivity and antibacterial properties emerged as a promising biomaterial to be applied for dentistry and orthopedic implantology.

In vivo biocompatibility of diamond-like carbon films containing TiO2 nanoparticles for biomedical applications.

Hybrid diamond-like carbon (DLC) with incorporated titanium dioxide (TiO2) nanoparticle coatings have low friction coefficient, high wear resistance, high hardness, biocompatibility, and high chemical stability. They could be employed to modify biomedical alloys surfaces for numerous applications in biomedical engineering. Here we investigate for the first time the in vivo inflammatory process of DLC coatings with incorporated TiO2 nanoparticles. TiO2-DLC films were grown on AISI 316 stainless-steel substrates using plasma-enhanced chemical vapor deposition. The coated substrates were implanted in CF1 mice peritoneum. The in vivo cytotoxicity and biocompatibility of the samples were analyzed from macrophage lavage. Analysis in the first weeks after implantation could be helpful to evaluate the acute cytotoxicity generated after a possible inflammatory process. The in vivo results showed no inflammatory process. A significant increase in nitric oxide production on the uncoated substrates was confirmed through cytometry, and the coated substrates demonstrated biocompatibility. The presence of TiO2 nanoparticles enhanced the wound healing activity, due to their astringent and antimicrobial properties. DLC and TiO2-DLC coatings were considered biocompatible, and the presence of TiO2 nanoparticles reduced the inflammatory reactions, increasing DLC biocompatibility.

High-Density Three-Dimensional Network of Covalently Linked Nitric Oxide Donors to Achieve Antibacterial and Antibiofilm Surfaces.

Bacterial colonization on biomedical devices often leads to biofilms that are recalcitrant to antibiotic treatment and the leading cause of hospital-acquired infections. We have invented a novel pretreatment chemistry for device surfaces to produce a high-density three-dimensional (3-D) network of covalently linked S-nitrosothiol (RSNO), which is a nitric oxide (NO) donor. Poly(polyethylene glycol-hydroxyl-terminated) (i.e., PPEG-OH) brushes were grafted from an ozone-pretreated polyurethane (PU) surface. The high-density hydroxyl groups on the dangling PPEG-OH brushes then underwent condensation with a mercapto-silane (i.e., MPS, mercaptopropyl trimethoxysilane) followed by S-nitrosylation to produce a 3-D network of NO-releasing RSNO to form the PU/PPEG-OH-MPS-NO coating. This 3-D coating produces NO flux of up to 7 nmol/(cm2 min), which is nearly 3 orders of magnitude higher than the picomole/(cm2 min) levels of other NO-releasing biomedical implants previously reported. The covalent immobilization of RSNO avoids donor leaching and reduces the risks of cytotoxicity arising from leachable RSNO. Our coated PU surfaces display good biocompatibility and exhibit excellent antibiofilm formation activity in vitro (up to 99.99%) against a broad spectrum of Gram-positive and Gram-negative bacteria. Further, the high-density RSNO achieves nearly 99% and 99.9% in vivo reduction of Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) in a murine subcutaneous implantation infection model. Our surface chemistry to create high NO payload without NO-donor leaching can be applied to many biomedical devices.

One-Step Synthesis of Versatile Antimicrobial Nano-Architected Implant Coatings for Hard and Soft Tissue Healing.

Dental implant failure remains a prevalent problem around the globe. The integration of implants at the interface of soft and hard tissues is complex and susceptible to instability and infections. Modifications to the surface of titanium implants have been developed to improve the performance, yet insufficient integration and biofilm formation remain major problems. Introducing nanostructures on the surface to augment the implant-tissue contact holds promise for facilitated implant integration; however, current coating processes are limited in their versatility or costs. We present a highly modular single-step approach to produce multicomponent porous bioactive nanostructured coatings on implants. Inorganic nanoparticle building blocks with complex compositions and architectures are synthesized in situ and deposited on the implants in a single step using scalable liquid-feed flame spray pyrolysis. We present hybrid coatings based on ceria and bioglass, which render the implant surfaces superhydrophilic, promote cell adhesion, and exhibit antimicrobial properties. By modifications to the bioglass/ceria nanohybrid composition and architecture that prevent biomineralization, the coating can instead be tailored toward soft tissue healing. The one-step synthesis of nano-architected tissue-specific coatings has great potential in dental implantology and beyond.