Alex Cavallaro

Enzyme responsive hyaluronic acid nanocapsules containing polyhexanide and their exposure to bacteria to prevent infection.

Antibacterial nanodevices could bring coatings of plastic materials and wound dressings a big step forward if the release of the antibacterial agents could be triggered by the presence of the bacteria themselves. Here, we show that novel hyaluronic acid (HA)-based nanocapsules containing the antimicrobial agent polyhexanide are specifically cleaved in the presence of hyaluronidase, a factor of pathogenicity and invasion for bacteria like Staphylococcus aureus and Escherichia coli. This resulted in an efficient killing of the pathogenic bacteria by the antimicrobial agent. The formation of different polymeric nanocapsules was achieved through a polyaddition reaction in inverse miniemulsion. After the synthesis, the nanocapsules were transferred to an aqueous medium and investigated in terms of size, size distribution, functionality, and morphology using dynamic light scattering, zeta potential measurements and scanning electron microscopy. The enzyme triggered release of a model dye and the antimicrobial polyhexanide was monitored using fluorescence and UV spectroscopy. The stability of the nanocapsules in several biological media was tested and the interaction of nanocapsules with human serum protein was studied using isothermal titration calorimetry. The antibacterial effectiveness is demonstrated by determination of the antibacterial activity and determination of the minimal bactericidal concentration (MBC).

Fabrication of stimulus-responsive diatom biosilica microcapsules for antibiotic drug delivery

In this report, we employed surface-initiated atom transfer radical polymerisation to graft thermo-responsive copolymers of oligo(ethylene glycol) methacrylates from the surface of diatom biosilica microcapsules. We demonstrate the application of the resulting composites for thermo-responsive drug delivery.

Nitric oxide-releasing porous silicon nanoparticles

In this study, the ability of porous silicon nanoparticles (PSi NPs) to entrap and deliver nitric oxide (NO) as an effective antibacterial agent is tested against different Gram-positive and Gram-negative bacteria. NO was entrapped inside PSi NPs functionalized by means of the thermal hydrocarbonization (THC) process. Subsequent reduction of nitrite in the presence of d-glucose led to the production of large NO payloads without reducing the biocompatibility of the PSi NPs with mammalian cells. The resulting PSi NPs demonstrated sustained release of NO and showed remarkable antibacterial efficiency and anti-biofilm-forming properties. These results will set the stage to develop antimicrobial nanoparticle formulations for applications in chronic wound treatment.

Antibiofouling Properties of Plasma-Deposited Oxazoline-Based Thin Films

Infections caused by the bacterial colonization of medical devices are a substantial problem to patients and healthcare. Biopassive polyoxazoline coatings are attracting attention in the biomedical field as one of the potential solutions to this problem. Here, we present an original and swift way to produce plasma-deposited oxazoline-based films for antifouling applications. The films developed via the plasma deposition of 2-methyl-2-oxazoline and 2-ethyl-2-oxazoline have tunable thickness and surface properties. Diverse film chemistries were achieved by tuning and optimizing the deposition conditions. Human-derived fibroblasts were used to confirm the biocompatibility of oxazoline derived coatings. The capacity of the coatings to resist biofilm attachment was studied as a function of deposition power and mode (i.e., continuous wave or pulsed) and precursor flow rates for both 2-methyl-2-oxazoline and 2-ethyl-2-oxazoline. After careful tuning of the deposition parameters films having the capacity to resist biofilm formation by more than 90% were achieved. The substrate-independent and customizable properties of the new generation of plasma deposited oxazoline thin films developed in this work make them attractive candidates for the coating of medical devices and other applications where bacteria surface colonization and biofilm formation is an issue.

Properties and reactivity of polyoxazoline plasma polymer films

Polyoxazolines arise as a promising new class of polymers for biomedical applications, but creating oxzoline-based coatings via conventional methods is challenging. Herein, nanoscale polyoxazoline coatings were generated via a single step plasma deposition process. The effects of plasma deposition conditions on the film stability, structure and chemical group density were investigated. Detailed examination of the physical and chemical properties of plasma deposited polyoxazoline via XPS, FTIR, contact angle and ellipsometry unravels the complex functionality of the films. Partial retention of the oxazoline ring facilitates a covalent reaction with the carboxylic acid groups present on nanoparticles and biomolecules. Surface bound proteins effectively retain their bioactivity, therefore a vast range of potential applications unlocks for plasma deposited polyoxazoline coatings in the field of biosensing, medical arrays and diagnosis.

Influence of immobilized quaternary ammonium group surface density on antimicrobial efficacy and cytotoxicity

Abstract Bacterial colonization of medical devices causes infections and is a significant problem in healthcare. The use of antibacterial coatings is considered as a potential solution to this problem and has attracted a great deal of attention. Using concentration density gradients of immobilized quaternary ammonium compounds it was demonstrated that a specific threshold of surface concentration is required to induce significant bacterial death. It was determined that this threshold was 4.18% NR4+ bonded nitrogen with a surface potential of + 120.4 mV. Furthermore, it is shown for the first time that adhesion of constituents of the culture medium to the quaternary ammonium modified surface eliminated any cytotoxicity towards eukaryotic cells such as primary human fibroblasts. The implications of this type of surface fouling on the antimicrobial efficacy of surface coatings are also discussed.

Silver nanoparticle based coatings enhance adipogenesis compared to osteogenesis in human mesenchymal stem cells through oxidative stress

Silver nanoparticle (AgNP) based antibacterial surfaces were fabricated using plasma polymerization technology and their effects on differentiation of human bone-marrow derived mesenchymal stem cells (hMSCs) were investigated in this study. The results showed that AgNP coated surfaces do not affect the initial adhesion, spreading and proliferation of hMSCs. Furthermore, the silver coated surface promoted adipogenic differentiation of hMSCs as demonstrated by more accumulation of lipid droplets and upregulation of adipogenesis-related genes such as peroxisome proliferator activated receptor gamma (PPARγ), adipocyte determination and differentiation factor (ADD1) and CCAAT/enhancer binding protein alpha (C/EBPα). In addition, silver incorporation activated the expression of antioxidant enzymes as a consequence of the accumulation of intracellular reactive oxygen species (ROS) in adipogenic induced cells, which was correlated with the enhanced adipogenic capacity of hMSCs. ROS generation was enhanced due to silver ion release and consequently reduced osteogenesis at the early stage after 7 days of osteogenic induction as a result of reducing alkaline phosphatase (ALP) activity. However, the differentiation and mineralization capacity of osteoblasts were restored after 14 days of osteogenic induction, which indicated that adipogenesis favors intracellular ROS accumulation mediated by silver coatings compared to osteogenesis. None of the osteogenic related genes was affected by ROS mediated by AgNP dissolution. The findings in this work are instructive for the use of silver as an antibacterial agent in the areas of tissue engineering, stem cell therapies and implantable biomedical devices.

Antibacterial properties of silver dendrite decorated silicon nanowires

In this work, we report on the antibacterial properties of silicon nanowires (SiNWs) generated by via metal-assisted chemical etching (MACE) against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria strains. The results demonstrate that the antibacterial action can be attributed to the layer of silver (Ag) dendrites found on the surface of the SiNWs as a natural by-product of the MACE reaction, thus eliminating the need for a second surface modification step with an antibacterial agent. Furthermore, a 100 fold increase in bacterial adherence to SiNWs by virtue of their unique morphology is also demonstrated compared to flat silicon. We observed negligible toxicity exhibited by the SiNWs towards mammalian cells, in addition to very low rates of attachment of the mammalian cells to the SiNWs. This combination of characteristics makes these nanowire substrates an interesting alternative to other biomaterials for use in medical implants and wound dressings to combat bacterial infections.

Antibacterial properties of nitric oxide-releasing porous silicon nanoparticles

In this study, the antibacterial efficacy of NO-releasing porous silicon nanoparticles (pSiNPs) is reported. NO-releasing pSiNPs were produced via the conjugation of S-nitrosothiol (SNO) and S-nitrosoglutathione (GSNO) donors to the nanoparticle surfaces. The release of the conjugated NO caused by the decomposition of the conjugated SNO and GSNO was boosted in the presence of ascorbic acid. The released NO was bactericidal to Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli), and eliminated bacterial growth within 2 h of incubation without compromising the viability of mammalian cells. These results demonstrate the advantages of NO-releasing pSiNPs for antibacterial applications, for example, in chronic wound treatment.

Hybrid core/shell microparticles and their use for understanding biological processes.

Hybrid micro and nanoparticles have become a topic of intense research in recent years. This is due to the special properties of these materials that open new avenues in advanced applications. Herein, we report a novel method for the generation of hybrid particles utilising plasma polymerization. Poly (methyl methacrylate) (PMMA) beads were first coated with a thin allylamine based plasma polymer layer. Gold nanoparticles of engineered size and surface structure were then attached in a controlled manner to the plasma polymer coated beads. To generate uniform chemistry on the outermost surface and to preserve the nanotopography, we deposited a 5-10 nm thin layer of Acpp. We demonstrated that these particles can be utilized in in vivo models to interrogate important biological phenomena. Specifically, we used them in mice to study the inflammatory and foreign body responses to surface nanotopography. The data strongly indicates that surface nanotopography and chemistry can modulate collagen production and the number of adhering immune cells. The method for generating hybrid particles reported here is solvent free and can open new opportunities in fields such as tissue engineering, drug delivery, biosensors, and regenerative medicine.