MAPLE Processed Nanostructures for Antimicrobial Coatings.

Despite their great benefits for debilitated patients, indwelling devices are prone to become easily colonized by resident and opportunistic microorganisms, which have the ability to attach to their surfaces and form highly specialized communities called biofilms. These are extremely resistant to host defense mechanisms and antibiotics, leading to treatment failure and device replacement, but also to life-threatening complications. In this study, we aimed to optimize a silica (SiO2)-coated magnetite (Fe3O4)-based nanosystem containing the natural antimicrobial agent, eugenol (E), suitable for MAPLE (matrix-assisted pulsed laser evaporation) deposition as a bioactive coating for biomedical applications. X-ray diffraction, thermogravimetric analysis, Fourier-transform infrared spectroscopy, and transmission electron microscopy investigations were employed to characterize the obtained nanosystems. The in vitro tests evidenced the superior biocompatibility of such nanostructured coatings, as revealed by their non-cytotoxic activity and ability to promote cellular proliferation and sustain normal cellular development of dermal fibroblasts. Moreover, the obtained nanocoatings did not induce proinflammatory events in human blood samples. Our studies demonstrated that Fe3O4 NPs can improve the antimicrobial activity of E, while the use of a SiO2 matrix may increase its efficiency over prolonged periods of time. The Fe3O4@SiO2 nanosystems showed excellent biocompatibility, sustaining human dermal fibroblasts' viability, proliferation, and typical architecture. More, the novel coatings lack proinflammatory potential as revealed by the absence of proinflammatory cytokine expression in response to human blood sample interactions.

Isoflavonoid-Antibiotic Thin Films Fabricated by MAPLE with Improved Resistance to Microbial Colonization.

Staphylococcus aureus (Gram-positive) and Pseudomonas aeruginosa (Gram-negative) bacteria represent major infectious threats in the hospital environment due to their wide distribution, opportunistic behavior, and increasing antibiotic resistance. This study reports on the deposition of polyvinylpyrrolidone/antibiotic/isoflavonoid thin films by the matrix-assisted pulsed laser evaporation (MAPLE) method as anti-adhesion barrier coatings, on biomedical surfaces for improved resistance to microbial colonization. The thin films were characterized by Fourier transform infrared spectroscopy, infrared microscopy, and scanning electron microscopy. In vitro biological assay tests were performed to evaluate the influence of the thin films on the development of biofilms formed by Gram-positive and Gram-negative bacterial strains. In vitro biocompatibility tests were assessed on human endothelial cells examined for up to five days of incubation, via qualitative and quantitative methods. The results of this study revealed that the laser-fabricated coatings are biocompatible and resistant to microbial colonization and biofilm formation, making them successful candidates for biomedical devices and contact surfaces that would otherwise be amenable to contact transmission.

Nanostructured Thin Coatings Containing Anthriscus sylvestris Extract with Dual Bioactivity.

Plant extracts are highly valuable pharmaceutical complexes recognized for their biological properties, including antibacterial, antifungal, antiviral, antioxidant, anticancer, and anti-inflammatory properties. However, their use is limited by their low water solubility and physicochemical stability. In order to overcome these limitations, we aimed to develop nanostructured carriers as delivery systems for plant extracts; in particular, we selected the extract of Anthriscus sylvestris (AN) on the basis of its antimicrobial effect and antitumor activity. In this study, AN-extract-functionalized magnetite (Fe3O4@AN) nanoparticles (NPs) were prepared by the co-precipitation method. The purpose of this study was to synthesize and investigate the physicochemical and biological features of composite coatings based on Fe3O4@AN NPs obtained by matrix-assisted pulsed laser evaporation technique. In this respect, laser fluence and drop-casting studies on coatings were performed. The physical and chemical properties of laser-synthesized coatings were investigated by scanning electron microscopy, while Fourier transform infrared spectroscopy comparative analysis was used for determining the chemical structure and functional integrity. Relevant data regarding the presence of magnetic nanoparticles as the only crystalline phase and the size of nanoparticles were obtained by transmission electron microscopy. The in vitro toxicity assessment of the Fe3O4@AN showed significant cytotoxic activity against human adenocarcinoma HT-29 cells after prolonged exposure. Antimicrobial results demonstrated that Fe3O4@AN coatings inhibit microbial colonization and biofilm formation in clinically relevant bacteria species and yeasts. Such coatings are useful, natural, and multifunctional solutions for the development of tailored medical devices and surfaces.

Treatment Strategies for Infected Wounds.

The treatment of skin wounds is a key research domain owing to the important functional and aesthetic role of this tissue. When the skin is impaired, bacteria can soon infiltrate into underlying tissues which can lead to life-threatening infections. Consequently, effective treatments are necessary to deal with such pathological conditions. Recently, wound dressings loaded with antimicrobial agents have emerged as viable options to reduce wound bacterial colonization and infection, in order to improve the healing process. In this paper, we present an overview of the most prominent antibiotic-embedded wound dressings, as well as the limitations of their use. A promising, but still an underrated group of potential antibacterial agents that can be integrated into wound dressings are natural products, especially essential oils. Some of the most commonly used essential oils against multidrug-resistant microorganisms, such as tea tree, St. John's Wort, lavender and oregano, together with their incorporation into wound dressings are presented. In addition, another natural product that exhibits encouraging antibacterial activity is honey. We highlight recent results of several studies carried out by researchers from different regions of the world on wound dressings impregnated with honey, with a special emphasis on Manuka honey. Finally, we highlight recent advances in using nanoparticles as platforms to increase the effect of pharmaceutical formulations aimed at wound healing. Silver, gold, and zinc nanoparticles alone or functionalized with diverse antimicrobial compounds have been integrated into wound dressings and demonstrated therapeutic effects on wounds.

Functionalized Antimicrobial Composite Thin Films Printing for Stainless Steel Implant Coatings.

In this work we try to address the large interest existing nowadays in the better understanding of the interaction between microbial biofilms and metallic implants. Our aimed was to identify a new preventive strategy to control drug release, biofilm formation and contamination of medical devices with microbes. The transfer and printing of novel bioactive glass-polymer-antibiotic composites by Matrix-Assisted Pulsed Laser Evaporation into uniform thin films onto 316 L stainless steel substrates of the type used in implants are reported. The targets were prepared by freezing in liquid nitrogen mixtures containing polymer and antibiotic reinforced with bioglass powder. The cryogenic targets were submitted to multipulse evaporation by irradiation with an UV KrF* (λ = 248 nm, τFWHM ≤ 25 ns) excimer laser source. The prepared structures were analyzed by infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy and profilometry, before and after immersion in physiological fluids. The bioactivity and the release of the antibiotic have been evaluated. We showed that the incorporated antibiotic underwent a gradually dissolution in physiological fluids thus supporting a high local treatment efficiency. Electrochemical measurements including linear sweep voltammetry and impedance spectroscopy studies were carried out to investigate the corrosion resistance of the coatings in physiological environments. The in vitro biocompatibility assay using the MG63 mammalian cell line revealed that the obtained nanostructured composite films are non-cytotoxic. The antimicrobial effect of the coatings was tested against Staphylococcus aureus and Escherichia coli strains, usually present in implant-associated infections. An anti-biofilm activity was evidenced, stronger against E. coli than the S. aureus strain. The results proved that the applied method allows for the fabrication of implantable biomaterials which shield metal ion release and possess increased biocompatibility and resistance to microbial colonization and biofilm growth.

Polymersomes as Innovative, Stimuli-Responsive Platforms for Cancer Therapy.

This review addresses the urgent need for more targeted and less toxic cancer treatments by exploring the potential of multi-responsive polymersomes. These advanced nanocarriers are engineered to deliver drugs precisely to tumor sites by responding to specific stimuli such as pH, temperature, light, hypoxia, and redox conditions, thereby minimizing the side effects associated with traditional chemotherapy. We discuss the design, synthesis, and recent applications of polymersomes, emphasizing their ability to improve therapeutic outcomes through controlled drug release and targeted delivery. Moreover, we highlight the critical areas for future research, including the optimization of polymersome-biological interactions and biocompatibility, to facilitate their clinical adoption. Multi-responsive polymersomes emerge as a promising development in nanomedicine, offering a pathway to safer and more effective cancer treatments.

Integrating Artificial Intelligence for Drug Discovery in the Context of Revolutionizing Drug Delivery.

Drug development is expensive, time-consuming, and has a high failure rate. In recent years, artificial intelligence (AI) has emerged as a transformative tool in drug discovery, offering innovative solutions to complex challenges in the pharmaceutical industry. This manuscript covers the multifaceted role of AI in drug discovery, encompassing AI-assisted drug delivery design, the discovery of new drugs, and the development of novel AI techniques. We explore various AI methodologies, including machine learning and deep learning, and their applications in target identification, virtual screening, and drug design. This paper also discusses the historical development of AI in medicine, emphasizing its profound impact on healthcare. Furthermore, it addresses AI's role in the repositioning of existing drugs and the identification of drug combinations, underscoring its potential in revolutionizing drug delivery systems. The manuscript provides a comprehensive overview of the AI programs and platforms currently used in drug discovery, illustrating the technological advancements and future directions of this field. This study not only presents the current state of AI in drug discovery but also anticipates its future trajectory, highlighting the challenges and opportunities that lie ahead.

Polymeric Micellar Systems-A Special Emphasis on "Smart" Drug Delivery.

Concurrent developments in anticancer nanotechnological treatments have been observed as the burden of cancer increases every year. The 21st century has seen a transformation in the study of medicine thanks to the advancement in the field of material science and nanomedicine. Improved drug delivery systems with proven efficacy and fewer side effects have been made possible. Nanoformulations with varied functions are being created using lipids, polymers, and inorganic and peptide-based nanomedicines. Therefore, thorough knowledge of these intelligent nanomedicines is crucial for developing very promising drug delivery systems. Polymeric micelles are often simple to make and have high solubilization characteristics; as a result, they seem to be a promising alternative to other nanosystems. Even though recent studies have provided an overview of polymeric micelles, here we included a discussion on the "intelligent" drug delivery from these systems. We also summarized the state-of-the-art and the most recent developments of polymeric micellar systems with respect to cancer treatments. Additionally, we gave significant attention to the clinical translation potential of polymeric micellar systems in the treatment of various cancers.

Exploring the Potential of Artificial Intelligence for Hydrogel Development-A Short Review.

AI and ML have emerged as transformative tools in various scientific domains, including hydrogel design. This work explores the integration of AI and ML techniques in the realm of hydrogel development, highlighting their significance in enhancing the design, characterisation, and optimisation of hydrogels for diverse applications. We introduced the concept of AI train hydrogel design, underscoring its potential to decode intricate relationships between hydrogel compositions, structures, and properties from complex data sets. In this work, we outlined classical physical and chemical techniques in hydrogel design, setting the stage for AI/ML advancements. These methods provide a foundational understanding for the subsequent AI-driven innovations. Numerical and analytical methods empowered by AI/ML were also included. These computational tools enable predictive simulations of hydrogel behaviour under varying conditions, aiding in property customisation. We also emphasised AI's impact, elucidating its role in rapid material discovery, precise property predictions, and optimal design. ML techniques like neural networks and support vector machines that expedite pattern recognition and predictive modelling using vast datasets, advancing hydrogel formulation discovery are also presented. AI and ML's have a transformative influence on hydrogel design. AI and ML have revolutionised hydrogel design by expediting material discovery, optimising properties, reducing costs, and enabling precise customisation. These technologies have the potential to address pressing healthcare and biomedical challenges, offering innovative solutions for drug delivery, tissue engineering, wound healing, and more. By harmonising computational insights with classical techniques, researchers can unlock unprecedented hydrogel potentials, tailoring solutions for diverse applications.

Spectral Analysis of Strontium-Doped Calcium Phosphate/Chitosan Composite Films.

Strontium-doped calcium phosphate/chitosan films were synthetized on silicon substrates using the radio-frequency magnetron sputtering technique and the matrix-assisted pulsed laser evaporation technique. The deposition conditions associated with the radio-frequency magnetron sputtering discharge, in particular, include the high temperature at the substrate, which promotes the formation of strontium-doped tetra calcium phosphate layers. The physical and chemical processes associated with the deposition of chitosan on strontium-doped calcium phosphate layers were investigated using Fourier Transform Infrared Spectroscopy, Energy Dispersive X-ray Spectroscopy, and Scanning Electron Microscopy. Mass spectrometry coupled with laser induced ablation of the composite films proved to be a useful tool in the detection of the molecular ions characteristic to chitosan chemical structure.

Bioglass and Vitamin D3 Coatings for Titanium Implants: Osseointegration and Corrosion Protection.

The use of MAPLE synthesized thin films based on BG and VD3 for improving the osseointegration and corrosion protection of Ti-like implant surfaces is reported. The distribution of chemical elements and functional groups was shown by FTIR spectrometry; the stoichiometry and chemical functional integrity of thin films after MAPLE deposition was preserved, optimal results being revealed especially for the BG+VD3_025 samples. The morphology and topography were examined by SEM and AFM, and revealed surfaces with many irregularities, favoring a good adhesion of cells. The thin films' cytotoxicity and biocompatibility were evaluated in vitro at the morphological, biochemical, and molecular level. Following incubation with HDF cells, BG57+VD3_ 025 thin films showed the best degree of biocompatibility, as illustrated by the viability assay values. According to the LDH investigation, all tested samples had higher values compared to the unstimulated cells. The evaluation of cell morphology was performed by fluorescence microscopy following cultivation of HDF cells on the obtained thin films. The cultivation of HDF's on the thin films did not induce major cellular changes. Cells cultured on the BG57+VD3_025 sample had similar morphology to that of unstimulated control cells. The inflammatory profile of human cells cultured on thin films obtained by MAPLE was analyzed by the ELISA technique. It was observed that the thin films did not change the pro- and anti-inflammatory profile of the HDF cells, the IL-6 and IL-10 levels being similar to those of the control sample. The wettability of the MAPLE thin films was investigated by the sessile drop method. A contact angle of 54.65° was measured for the sample coated with BG57+VD3_025. Electrochemical impedance spectroscopy gave a valuable insight into the electrochemical reactions occurring on the surface.

Polymeric Coatings and Antimicrobial Peptides as Efficient Systems for Treating Implantable Medical Devices Associated-Infections.

Many infections are associated with the use of implantable medical devices. The excessive utilization of antibiotic treatment has resulted in the development of antimicrobial resistance. Consequently, scientists have recently focused on conceiving new ways for treating infections with a longer duration of action and minimum environmental toxicity. One approach in infection control is based on the development of antimicrobial coatings based on polymers and antimicrobial peptides, also termed as "natural antibiotics".

Calcium Phosphates-Chitosan Composite Layers Obtained by Combining Radio-Frequency Magnetron Sputtering and Matrix-Assisted Pulsed Laser Evaporation Techniques.

In this work, we report the synthesis of calcium phosphate-chitosan composite layers. Calcium phosphate layers were deposited on titanium substrates by radio-frequency magnetron sputtering technique by varying the substrate temperature from room temperature (25 °C) up to 100 and 300 °C. Further, chitosan was deposited by matrix-assisted pulsed laser evaporation technique on the calcium phosphate layers. The temperature at the substrate during the deposition process of calcium phosphate layers plays an important role in the embedding of chitosan, as scanning electron microscopy analysis showed. The degree of chitosan incorporation into the calcium phosphate layers significantly influence the physico-chemical properties and the adherence strength of the resulted layers to the substrates. For example, the decreases of Ca/P ratio at the addition of chitosan suggests that a calcium deficient hydroxyapatite structure is formed when the CaP layers are generated on Ti substrates kept at room temperature during the deposition process. The Fourier transform infrared spectroscopy analysis of the samples suggest that the PO43-/CO32- substitution is possible. The X-ray diffraction spectra indicated that the crystalline structure of the calcium phosphate layers obtained at the 300 °C substrate temperature is disturbed by the addition of chitosan. The adherence strength of the composite layers to the titanium substrates is diminished after the chitosan deposition. However, no complete exfoliation of the layers was observed.

Pulsed Laser Photo-Crosslinking of Gelatin Methacryloyl Hydrogels for the Controlled Delivery of Chlorpromazine to Combat Antimicrobial Resistance.

Hydrogels are ideal candidates for the sustained local administration of antimicrobial drugs because they have customizable physicochemical properties that allow drug release kinetics to be controlled and potentially address the issue of systemic side effects. Consequently, the purpose of this study was to use 266 nm-pulsed laser beams to photo-crosslink gelatin methacryloyl hydrogels using Irgacure 2959 as a photo-initiator to reduce the curing time and to have an online method to monitor the process, such as laser-induced fluorescence. Additionally, irradiated chlorpromazine was loaded into the hydrogels to obtain a drug delivery system with antimicrobial activity. These hydrogels were investigated by UV-Vis and FTIR absorption spectroscopy, scanning electron microscopy, and laser-induced fluorescence spectroscopy and their structural and morphological characteristics, swelling behavior, and drug release profile were obtained. As a result the morphology, swelling behavior, and drug release profile were influenced by both the energy of the laser beam and the exposure time. The optimal hydrogel was obtained after 1 min of laser irradiation for Irgacure 2959 at 0.05% w/v concentration and gelatin methacryloyl at 10% w/v concentration. The hydrogels loaded with irradiated chlorpromazine show significant antimicrobial activity against Staphylococcus aureus and MRSA bacteria and a non-cytotoxic effect against L929 fibroblast cell lines.

Composite Coatings for Osteoblast Growth Attachment Fabricated by Matrix-Assisted Pulsed Laser Evaporation.

The bioactive and biocompatible properties of hydroxyapatite (HAp) promote the osseointegration process. HAp is widely used in biomedical applications, especially in orthopedics, as well as a coating material for metallic implants. We obtained composite coatings based on HAp, chitosan (CS), and FGF2 by a matrix-assisted pulsed laser evaporation (MAPLE) technique. The coatings were physico-chemically investigated by means of X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Infrared Microscopy (IRM), and Scanning Electron Microscopy (SEM). Further, biological investigations were performed. The MAPLE-composite coatings were tested in vitro on the MC3T3-E1 cell line in order to endorse cell attachment and growth without toxic effects and to promote pre-osteoblast differentiation towards the osteogenic lineage. These coatings can be considered suitable for bone tissue engineering applications that lack toxicity and promotes cell adhesion and proliferation while also sustaining the differentiation of pre-osteoblasts towards mature bone cells.

Implant Surfaces Containing Bioglasses and Ciprofloxacin as Platforms for Bone Repair and Improved Resistance to Microbial Colonization.

Coatings are an attractive and challenging selection for improving the bioperformance of metallic devices. Composite materials based on bioglass/antibiotic/polymer are herein proposed as multifunctional thin films for hard tissue implants. We deposited a thin layer of the polymeric material by matrix-assisted pulsed laser evaporation-MAPLE onto Ti substrates. A second layer consisting of bioglass + antibiotic was applied by MAPLE onto the initial thin film. The antimicrobial activity of MAPLE-deposited thin films was evaluated on Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa standard strains. The biocompatibility of obtained thin films was assessed on mouse osteoblast-like cells. The results of our study revealed that the laser-deposited coatings are biocompatible and resistant to microbial colonization and biofilm formation. Accordingly, they can be considered viable candidates for biomedical devices and contact surfaces that would otherwise be amenable to contact transmission.

Experimental Investigation on Water Adsorption Using Laser Photoacoustic Spectroscopy and Numerical Simulations.

In the present research we propose a model to assess the water vapors adsorption capacity of a SiO2 trap in the breathing circuit, aiming to reduce the loading of interfering compounds in human breath samples. In this study we used photoacoustic spectroscopy to analyze the SiO2 adsorption of interfering compounds from human breath and numerical simulations to study the flow of expired breath gas through porous media. As a result, the highest adsorption rate was achieved with a flow rate of 300 sccm, while the lowest rate was achieved with a flow rate of 600 sccm. In the procedure of H2O removal from the human breath air samples, we determined a quantity of 213 cm3 SiO2 pearls to be used for a 750 mL sampling bag, in order to keep the detection of ethylene free of H2O interference. The data from this study encourages the premise that the SiO2 trap is efficient in the reduction of interfering compounds (like water vapors) from the human breath.

Bioactive Coatings Loaded with Osteogenic Protein for Metallic Implants.

Osteoconductive and osteoinductive coatings represent attractive and tunable strategies towards the enhanced biomechanics and osseointegration of metallic implants, providing accurate local modulation of bone-to-implant interface. Composite materials based on polylactide (PLA) and hydroxyapatite (HAp) are proved beneficial substrates for the modulation of bone cells' development, being suitable mechanical supports for the repair and regeneration of bone tissue. Moreover, the addition of osteogenic proteins represents the next step towards the fabrication of advanced biomaterials for hard tissue engineering applications, as their regulatory mechanisms beneficially contribute to the new bone formation. In this respect, laser-processed composites, based on PLA, Hap, and bone morphogenetic protein 4(BMP4), are herein proposed as bioactive coatings for metallic implants. The nanostructured coatings proved superior ability to promote the adhesion, viability, and proliferation of osteoprogenitor cells, without affecting their normal development and further sustaining the osteogenic differentiation of the cells. Our results are complementary to previous studies regarding the successful use of chemically BMP-modified biomaterials in orthopedic and orthodontic applications.

Anti-Cancer Nanopowders and MAPLE-Fabricated Thin Films Based on SPIONs Surface Modified with Paclitaxel Loaded ß-Cyclodextrin.

Globally, cancer is the second most common cause of death, and Europe accounts for almost 25% of the global cancer burden, although its people make up only 10% of the world's population. Conventional systemically administered anti-cancer drugs come with important drawbacks such as inefficiency due to poor bioavailability and improper biodistribution, severe side effects associated with low therapeutic indices, and the development of multidrug resistance. Therefore, smart nano-engineered targeted drug-delivery systems with tailored pharmacokinetics and biodistribution which can selectively deliver anti-cancer agents directly to the tumor site are the solution to most difficulties encountered with conventional therapeutic tools. Here, we report on the synthesis, physicochemical characterization, and in vitro evaluation of biocompatibility and anti-tumor activity of novel magnetically targetable SPIONs based on magnetite (Fe3O4) nanoparticles' surface modified with ß-cyclodextrin (CD) and paclitaxel (PTX)-guest-host inclusion complexes (Fe3O4@ß-CD/PTX). Both pristine Fe3O4@ß-CD nanopowders and PTX-loaded thin films fabricated by MAPLE technique were investigated. Pristine Fe3O4@ß-CD and Fe3O4@ß-CD/PTX thin films were physicochemically characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The biocompatibility of bare magnetic nanocomposite thin films was evaluated by MTT cell viability assay on a normal 3T3 osteoblast cell line culture and by measuring the level of NO in the culture medium. No significant modifications, neither in cell viability nor in NO level, could be observed, thereby demonstrating the excellent biocompatibility of the SPIONs thin films. Inverted phase-contrast microscopy showed no evident adverse effect on the morphology of normal osteoblasts. On the other hand, Fe3O4@ß-CD/PTX films decreased the cell viability of the MG-63 osteosarcoma cell line by 85%, demonstrating excellent anti-tumor activity. The obtained results recommend these magnetic hybrid films as promising candidates for future delivery, and hyperthermia applications in cancer treatment.

Bioactive Coatings Based on Hydroxyapatite, Kanamycin, and Growth Factor for Biofilm Modulation.

The occurrence of opportunistic local infections and improper integration of metallic implants results in severe health conditions. Protective and tunable coatings represent an attractive and challenging selection for improving the metallic devices' biofunctional performances to restore or replace bone tissue. Composite materials based on hydroxyapatite (HAp), Kanamycin (KAN), and fibroblast growth factor 2 (FGF2) are herein proposed as multifunctional coatings for hard tissue implants. The superior cytocompatibility of the obtained composite coatings was evidenced by performing proliferation and morphological assays on osteoblast cell cultures. The addition of FGF2 proved beneficial concerning the metabolic activity, adhesion, and spreading of cells. The KAN-embedded coatings exhibited significant inhibitory effects against bacterial biofilm development for at least two days, the results being superior in the case of Gram-positive pathogens. HAp-based coatings embedded with KAN and FGF2 protein are proposed as multifunctional materials with superior osseointegration potential and the ability to reduce device-associated infections.