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Objectives This study aimed to investigate the effect of erythritol air‐polishing on implant surface topography and bacterial colonization, and to determine the antimicrobial activity of erythritol powder. Materials and Methods Titanium implants, with machined/acid‐etched hybrid design, were divided into three groups: erythritol air‐polishing for 1 min (E1), 5 min (E5), and untreated control. Surface analysis was performed using a stylus profilometer and scanning electron microscope (SEM). To test the ability to prevent biofilm formation, four bacteria strains (Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus mutans, Streptococcus sanguinis) were separately cultured on five implants per group and colony counting was performed. The intrinsic erythritol antibacterial activity was investigated by means of minimum inhibitory concentration against the same strains. Results At SEM analysis implant surfaces appeared unaltered by air‐polishing and presented increasing amount of residues depending on the treatment duration. Machined surfaces exhibited no significant differences in roughness parameters between the groups. On acid‐etched surfaces, E5 presented significantly lower Ra (vs. E1 and control) and Rz (vs. control). The count of colonies was significantly lower for all bacterial strains on treated implants as compared to control, with E1 and E5 being equally capable to reduce by 1.5 log bacteria growth. Erythritol antimicrobial activity against all tested bacterial strains was confirmed. Conclusions The proposed erythritol air‐polishing protocols did not alter implant surfaces and the antimicrobial properties of erythritol are conserved by the titanium implant surfaces. Clinical Relevance Erythritol air‐polishing could be repeatedly used in supportive peri‐implant care programmes.

Bacteria primarily exist in robust, surface-associated communities known as biofilms, ubiquitous in both natural and anthropogenic environments. Mature biofilms resist a wide range of antimicrobial treatments and pose persistent pathogenic threats. Treatment of adherent biofilm is difficult, costly, and, in medical systems such as catheters or implants, frequently impossible. At the same time, strategies for biofilm prevention based on surface chemistry treatments or surface microstructure have been found to only transiently affect initial attachment. Here we report that Slippery Liquid-Infused Porous Surfaces (SLIPS) prevent 99.6% of Pseudomonas aeruginosa biofilm attachment over a 7-d period, as well as Staphylococcus aureus (97.2%) and Escherichia coli (96%), under both static and physiologically realistic flow conditions. In contrast, both polytetrafluoroethylene and a range of nanostructured superhydrophobic surfaces accumulate biofilm within hours. SLIPS show approximately 35 times the reduction of attached biofilm versus best case scenario, state-of-the-art PEGylated surface, and over a far longer timeframe. We screen for and exclude as a factor cytotoxicity of the SLIPS liquid, a fluorinated oil immobilized on a structured substrate. The inability of biofilm to firmly attach to the surface and its effective removal under mild flow conditions (about 1 cm/s) are a result of the unique, nonadhesive, “slippery” character of the smooth liquid interface, which does not degrade over the experimental timeframe. We show that SLIPS-based antibiofilm surfaces are stable in submerged, extreme pH, salinity, and UV environments. They are low-cost, passive, simple to manufacture, and can be formed on arbitrary surfaces. We anticipate that our findings will enable a broad range of antibiofilm solutions in the clinical, industrial, and consumer spaces.

Necroptosis is a regulated, nonapoptotic form of cell death initiated by receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL) proteins. It is considered to be a form of regulated necrosis, and, by lacking the \"find me\" and \"eat me\" signals that are a feature of apoptosis, necroptosis is considered to be inflammatory. One such \"eat me\" signal observed during apoptosis is the exposure of phosphatidylserine (PS) on the outer plasma membrane. Here, we demonstrate that necroptotic cells also expose PS after phosphorylated mixed lineage kinase-like (pMLKL) translocation to the membrane. Necroptotic cells that expose PS release extracellular vesicles containing proteins and pMLKL to their surroundings. Furthermore, inhibition of pMLKL after PS exposure can reverse the process of necroptosis and restore cell viability. Finally, externalization of PS by necroptotic cells drives recognition and phagocytosis, and this may limit the inflammatory response to this nonapoptotic form of cell death. The exposure of PS to the outer membrane and to extracellular vesicles is therefore a feature of necroptotic cell death and may serve to provide an immunologically-silent window by generating specific \"find me\" and \"eat me\" signals.

The surface that hates almost everything Inspired by the insect-eating Nepenthes pitcher plant, which snares its prey on a surface lubricated by a remarkably slippery aqueous secretion, Joanna Aizenberg and colleagues have synthesized omniphobic surfaces that can self-repair and function at high pressures. Their 'slippery liquid-infused porous surfaces' (or SLIPS) exhibit almost perfect slipperiness towards polar, organic and complex liquids. SLIPS function under extreme conditions, are easily constructed from inexpensive materials and can be endowed with other useful characteristics, such as enhanced optical transparency, through the selection of appropriate substrates and lubricants. Ultra-slippery surfaces of this type might find application in biomedical fluid handling, fuel transport, antifouling, anti-icing, optical imaging and elsewhere. Creating a robust synthetic surface that repels various liquids would have broad technological implications for areas ranging from biomedical devices and fuel transport to architecture but has proved extremely challenging 1 . Inspirations from natural nonwetting structures 2 , 3 , 4 , 5 , 6 , particularly the leaves of the lotus, have led to the development of liquid-repellent microtextured surfaces that rely on the formation of a stable air–liquid interface 7 , 8 , 9 . Despite over a decade of intense research, these surfaces are, however, still plagued with problems that restrict their practical applications: limited oleophobicity with high contact angle hysteresis 9 , failure under pressure 10 , 11 , 12 and upon physical damage 1 , 7 , 11 , inability to self-heal and high production cost 1 , 11 . To address these challenges, here we report a strategy to create self-healing, slippery liquid-infused porous surface(s) (SLIPS) with exceptional liquid- and ice-repellency, pressure stability and enhanced optical transparency. Our approach—inspired by Nepenthes pitcher plants 13 —is conceptually different from the lotus effect, because we use nano/microstructured substrates to lock in place the infused lubricating fluid. We define the requirements for which the lubricant forms a stable, defect-free and inert ‘slippery’ interface. This surface outperforms its natural counterparts 2 , 3 , 4 , 5 , 6 and state-of-the-art synthetic liquid-repellent surfaces 8 , 9 , 14 , 15 , 16 in its capability to repel various simple and complex liquids (water, hydrocarbons, crude oil and blood), maintain low contact angle hysteresis (<2.5°), quickly restore liquid-repellency after physical damage (within 0.1–1 s), resist ice adhesion, and function at high pressures (up to about 680 atm). We show that these properties are insensitive to the precise geometry of the underlying substrate, making our approach applicable to various inexpensive, low-surface-energy structured materials (such as porous Teflon membrane). We envision that these slippery surfaces will be useful in fluid handling and transportation, optical sensing, medicine, and as self-cleaning and anti-fouling materials operating in extreme environments.

Cerium oxide nanoparticles (nanoceria; CNPs) have been found to have both pro-oxidant and anti-oxidant effects on different cell systems or organisms. In order to untangle the mechanisms which underlie the biological activity of nanoceria, we have studied the effect of five different CNPs on a model relevant aquatic microorganism. Neither shape, concentration, synthesis method, surface charge (ζ-potential), nor nominal size had any influence in the observed biological activity. The main driver of toxicity was found to be the percentage of surface content of Ce 3+ sites: CNP1 (58%) and CNP5 (40%) were found to be toxic whereas CNP2 (28%), CNP3 (36%) and CNP4 (26%) were found to be non-toxic. The colloidal stability and redox chemistry of the most and least toxic CNPs, CNP1 and CNP2, respectively, were modified by incubation with iron and phosphate buffers. Blocking surface Ce 3+ sites of the most toxic CNP, CNP1, with phosphate treatment reverted toxicity and stimulated growth. Colloidal destabilization with Fe treatment only increased toxicity of CNP1. The results of this study are relevant in the understanding of the main drivers of biological activity of nanoceria and to define global descriptors of engineered nanoparticles (ENPs) bioactivity which may be useful in safer-by-design strategies of nanomaterials.

As a chronic metabolic disease, diabetes mellitus (DM) creates a hyperglycemic micromilieu around implants, resulting inthe high complication and failure rate of implantation because of mitochondrial dysfunction in hyperglycemia. To address the daunting issue, the authors innovatively devised and developed mitochondria‐targeted orthopedic implants consisted of nutrient element coatings and polyetheretherketone (PEEK). Dual nutrient elements, in the modality of ZnO and Sr(OH)2, are assembled onto the sulfonated PEEK surface (Zn&Sr‐SPEEK). The results indicate the synergistic liberation of Zn2+ and Sr2+ from coating massacres pathogenic bacteria and dramatically facilitates cyto‐activity of osteoblasts upon the hyperglycemic niche. Intriguingly, Zn&Sr‐SPEEK implants are demonstrated to have a robust ability to recuperate hyperglycemia‐induced mitochondrial dynamic disequilibrium and dysfunction by means of Dynamin‐related protein 1 (Drp1) gene down‐regulation, mitochondrial membrane potential (MMP) resurgence, and reactive oxygen species (ROS) elimination, ultimately enhancing osteogenicity of osteoblasts. In vivo evaluations utilizing diabetic rat femoral/tibia defect model at 4 and 8 weeks further confirm that nutrient element coatings substantially augment bone remodeling and osseointegration. Altogether, this study not only reveals the importance of Zn2+ and Sr2+ modulation on mitochondrial dynamics that contributes to bone formation and osseointegration, but also provides a novel orthopedic implant for diabetic patients with mitochondrial modulation capability. The synthesized dual nutrient element decorated implants enable to inhibit the overexpression of Drp1 gene, eliminate accumulated ROS of cells, recuperate MMP, ultimately contributing to regulating mitochondrial dynamics and functions, thereby enhancing osteogenicity of osteoblasts in hyperglycemia, which hold considerable promise for the future design of mitochondria‐targeted pathological implants.

Tumours growing in a sheet-like manner on the surface of organs and tissues with complex topologies represent a difficult-to-treat clinical scenario. Their complete surgical resection is difficult due to the complicated anatomy of the diseased tissue. Residual cancer often responds poorly to systemic therapy and locoregional treatment is hindered by the limited accessibility to microscopic tumour foci. Here we engineered a peptide-based surface-fill hydrogel (SFH) that can be syringe- or spray-delivered to surface cancers during surgery or used as a primary therapy. Once applied, SFH can shape change in response to alterations in tissue morphology that may occur during surgery. Implanted SFH releases nanoparticles composed of microRNA and intrinsically disordered peptides that enter cancer cells attenuating their oncogenic signature. With a single application, SFH shows efficacy in four preclinical models of mesothelioma, demonstrating the therapeutic impact of the local application of tumour-specific microRNA, which might change the treatment paradigm for mesothelioma and possibly other surface cancers. Tumours that grow on organ surfaces are difficult to eradicate as the complex topology of underlying tissues might hamper accessibility to tumour foci even after surgery. In this paper the authors engineer a peptide-based hydrogel that can be applied on surface tumours before or after resection, conform to the tissue underneath and release therapeutics.

Current research on dental implants has mainly focused on the influence of surface roughness on the rate of osseointegration, while studies on the development of surfaces to also improve the interaction of peri-implant soft tissues are lacking. To this end, the first purpose of this study was to evaluate the response of human gingival fibroblasts (hGDFs) to titanium implant discs (Implacil De Bortoli, Brazil) having different micro and nano-topography: machined (Ti-M) versus sandblasted/double-etched (Ti-S). The secondary aim was to investigate the effect of the macrogeometry of the discs on cells: linear-like (Ti-L) versus wave-like (Ti-W) surfaces. The atomic force microscopy (AFM) and scanning electron microscopy (SEM) analysis showed that the Ti-S surfaces were characterized by a significantly higher micro and nano roughness and showed the 3D macrotopography of Ti-L and Ti-W surfaces. For in vitro analyses, the hGDFs were seeded into titanium discs and analyzed at 1, 3, and 5 days for adhesion and morphology (SEM) viability and proliferation (Cck-8 and MTT assays). The results showed that all tested surfaces were not cytotoxic for the hGDFs, rather the nano-micro and macro topography favored their proliferation in a time-dependent manner. Especially, at 3 and 5 days, the number of cells on Ti-L was higher than on other surfaces, including Ti-W surfaces. In conclusion, although further studies are needed, our in vitro data proved that the use of implant discs with Ti-S surfaces promotes the adhesion and proliferation of gingival fibroblasts, suggesting their use for in vivo applications.

Biomedical applications of poly(ether ether ketone) (PEEK) are hindered by its inherent bioinertness and lack of osseointegration capability. In the present study, to enhance osteogenic activity and, hence, the osseointegration capability of PEEK, we proposed a strategy of combined phosphate and calcium surface-functionalization, in which ozone-gas treatment and wet chemistry were used for introduction of hydroxyl groups and modification of phosphate and/or calcium, respectively. Surface functionalization significantly elevated the surface hydrophilicity without changing the surface roughness or topography. The cell study demonstrated that immobilization of phosphate or calcium increased the osteogenesis of rat mesenchymal stem cells compared with bare PEEK, including cell proliferation, alkaline phosphatase activity, and bone-like nodule formation. Interestingly, further enhancement was observed for samples co-immobilized with phosphate and calcium. Furthermore, in the animal study, phosphate and calcium co-functionalized PEEK demonstrated significantly enhanced osseointegration, as revealed by a greater direct bone-to-implant contact ratio and bond strength between the bone and implant than unfunctionalized and phosphate-functionalized PEEK, which paves the way for the orthopedic and dental application of PEEK.

For a chronic infection to be established, bacteria must be able to cope with hostile conditions such as low iron levels, oxidative stress, and clearance by the host defense, as well as antibiotic treatment. It is generally accepted that biofilm formation facilitates tolerance to these adverse conditions. However, microscopic investigations of samples isolated from sites of chronic infections seem to suggest that some bacteria do not need to be attached to surfaces in order to establish chronic infections. In this study we employed scanning electron microscopy, confocal laser scanning microscopy, RT-PCR as well as traditional culturing techniques to study the properties of Pseudomonas aeruginosa aggregates. We found that non-attached aggregates from stationary-phase cultures have comparable growth rates to surface attached biofilms. The growth rate estimations indicated that, independently of age, both aggregates and flow-cell biofilm had the same slow growth rate as a stationary phase shaking cultures. Internal structures of the aggregates matrix components and their capacity to survive otherwise lethal treatments with antibiotics (referred to as tolerance) and resistance to phagocytes were also found to be strikingly similar to flow-cell biofilms. Our data indicate that the tolerance of both biofilms and non-attached aggregates towards antibiotics is reversible by physical disruption. We provide evidence that the antibiotic tolerance is likely to be dependent on both the physiological states of the aggregates and particular matrix components. Bacterial surface-attachment and subsequent biofilm formation are considered hallmarks of the capacity of microbes to cause persistent infections. We have observed non-attached aggregates in the lungs of cystic fibrosis patients; otitis media; soft tissue fillers and non-healing wounds, and we propose that aggregated cells exhibit enhanced survival in the hostile host environment, compared with non-aggregated bacterial populations.