Inspired by observations that the natural topography observed on cicada and dragonfly wings may be lethal to bacteria, researchers have sought to reproduce these nanostructures on biomaterials with the goal of reducing implant-associated infections. Titanium and its alloys are widely employed biomaterials with excellent properties but are susceptible to bacterial colonisation. Hydrothermal etching is a simple, cost-effective procedure which fabricates nanoscale protrusions of various dimensions upon titanium, depending on the etching parameters used. We investigated the role of etching time and the choice of cation (sodium and potassium) in the alkaline heat treatment on the topographical, physical, and bactericidal properties of the resulting modified titanium surfaces. Optimal etching times were 4 h for sodium hydroxide (NaOH) and 5 h for potassium hydroxide (KOH). NaOH etching for 4 h produced dense, but somewhat ordered, surface nanofeatures with 75 nanospikes per µm2. In comparison, KOH etching for 5 h resulted sparser but nonetheless disordered surface morphology with only 8 spikes per µm2. The NaOH surface was more effective at eliminating Gram-negative pathogens, while the KOH surface was more effective against the Gram-positive strains. These findings may guide further research and development of bactericidal titanium surfaces which are optimised for the predominant pathogens associated with the intended application.

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Peri-implantitis is a devastating oral disease that has given rise to a demand for improved implantable dental biomaterials that can integrate well into the supporting bone as well as resist bacterial colonization. Recent research has demonstrated that nanostructured titanium may be well positioned to meet this demand. An abundance of literature has established the in vitro efficacy of nanostructured titanium against bacteria cultured aerobically, but its efficacy against anaerobic bacteria relevant to dental infections remains unknown. In the present study, we engineered sharp, spikelike nanostructures on commercially pure titanium surfaces using hydrothermal etching and challenged them with three clinically relevant, anaerobic dental pathogens: Streptococcus mutans, Fusobacterium nucleatum, and Porphyromonas gingivalis. Our results demonstrated that titanium nanostructures bearing sharp protrusions can be effective at eliminating bacteria in anaerobic conditions, in both single-species (up to ∼94% cell death) and dual-species (up to ∼70% cell death) models. Furthermore, surface modification greatly enhanced the efficacy of azithromycin treatment against anaerobic dental pathogens, compared to a control titanium surface. At 2× MIC (minimum inhibitory concentration), azithromycin eliminated 99.4 ± 0.3% of S. mutans on the nanostructured surface within 10 days, while only 26% of the bacteria were killed on the control surface. A similar result was observed for P. gingivalis. The data presented here serve as a promising foundation of knowledge on which to build a greater understanding of how nanostructured biomaterials can be effective in anaerobic environments such as that found in the oral cavity.

The ever-increasing rate of medical device implantations is met by a proportionately high burden of implantassociated infections. To mitigate this threat, much research has been directed toward the development of antibacterial surface modifications by various means. One recent approach involves surfaces containing sharp nanostructures capable of killing bacteria upon contact. Herein, we report that the mechanical interaction between Staphylococcus aureus and such surface nanostructures leads to a sensitization of the pathogen to the glycopeptide antibiotic vancomycin. We demonstrate that this is due to cell wall damage and impeded bacterial defenses against reactive oxygen species. The results of this study promise to be impactful in the clinic, as a combination of nanostructured antibacterial surfaces and antibiotics commonly used in hospitals may improve antimicrobial therapy strategies, helping clinicians to prevent and treat implant-associated infections using reduced antibiotic concentrations instead of relying on invasive revision surgeries with often poor outcomes.

The superiority of titanium as a biomaterial is reflected in its corrosion resistance, mechanical strength, biocompatibility, and osseointegration capabilities. [1a] Although there is a high success rate associated with implanted devices, failure is not uncommon. One of the primary causes of implant failure is implantassociated infections (IAI). [2] In the field of orthopaedics, approximately 1-2% of joint replacement arthroplasties result in IAI. [3] The IAI rate is significantly higher in the periodontal field, with peri-implantitis seen in as many as 1 in 3 patients. [4] Infections involving fungal pathogens are emerging in both of these clinical fields, and Candida species are detected in as many as 90% of fungal IAI cases. [5] Candida albicans represents the most common fungal threat, but other notable species include Candida parapsilosis, Candida tropicalis, and Candida glabrata. [5d] In polymicrobial biofilms, C. albicans can protect Porphyromonas gingivalis from adverse conditions [6] and promote drug resistance in Staphylococcus aureus. [7] Its common occurrence in IAI can be attributed to the fact that C. albicans is found amongst the normal skin microbiota as a commensal microbe, and can occasionally translocate from the skin to the implanted device during surgery. [8] In a subset of the population, such as diabetics or those who have an otherwise compromised immune system, C. albicans can switch from its normal commensal state to an opportunistic pathogen. This is of particular concern because once a fungal infection becomes systemic, it is associated with a mortality rate of up to 50%. [9] In systemic candidiasis, the kidney is one of the primary organs to be affected, commonly leading to renal failure. [10] As a fungal pathogen, the virulence mechanisms of C. albicans differ from bacterial pathogens. One striking difference is the ability of pathogenic fungi to reversibly switch between two alternate phenotypes-an ovoid-shaped yeast phenotype and a filamentous hyphal phenotype, and this process is referred to as morphogenesis. [11] The yeast phenotype is associated with initial surface colonization, and later dissemination. The hyphal phenotype acts as structural support and promotes tissue invasion. [12] Invasion of host tissue allows C. albicans to enter the bloodstream and translocate around the body. Within the bloodstream, the presence of serum and the slightly alkaline pH provides ideal conditions for hyphal cell growth, which then allows the pathogen to invade There is a globally increasing demand for medically implanted devices, partly spurred by an aging population. In parallel, there is a proportionate increase in implant associated infection. Much focus has been directed toward the development of techniques to fabricate nanostructured antimicrobial biomaterials to mitigate infection. The present study investigates the interaction of the fungal pathogen Candida albicans with an antimicrobial surface bearing nanoscale protrusions. C. albicans cells were observed to be affected by cell ...