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We report on the Matrix Assisted Pulsed Laser Evaporation, laser technology for depositing biocompatible, antimicrobial, hydrophilic, and biodegradable complex hybrid polymeric system loaded with essential cypress-oil and magnetite nanoparticles as resorbable implants, capable of targeting possible hyperthermia applications, an anticancer moderate field heating therapy. Magnetite nanoparticles based on iron oxide (Fe3O4) coated with Cypress essential oil (denoted: Fe3O4- Cypress) and embedded in PLGA (poly(lactic-co-glycolic acid) (denoted: PLGA-Fe3O4- Cypress-) and PLGA - poly(3,4-ethylene dioxythiophene) doped with poly(styrene sulfonate) anions) (PEDOT: PSS) mixture (denoted: PLGA-Fe3O4- Cypress- PEDOT: PSS) were used as MAPLE targets. The controlled drug delivery of the active Cypress oil, an antimicrobial therapeutic agent from Fe3O4- Cypress nanoparticles could be possible by applying an external radio frequency (RF) magnetic field. The Fe3O4-Cypress-based powders as well as the final hybrid coatings have been characterized in terms of stoichiometry, morphology, magnetic, antimicrobial properties, biocompatibility, and response to external physical stimuli. FTIR analyses confirmed the quasi-stoichiometric laser transfer of organic compounds while the XRD evidenced the semicrystalline structure of deposited thin films. SEM and AFM images evidence that conductive polymer addition led to the films' relief flattening and a decrease in the coatings' thickness and roughness by changing the polymeric packaging. The samples containing conductive polymer exhibited 3 times higher current and corrosion rate values. All coatings are hydrophilic and revealed enhanced cellular viability when cultured with osteoblast-like MG-63 cells. The composite structures exhibited significant antimicrobial activity against Gram-positive (Staphylococcus aureus), and Gram-negative (Escherichia coli) bacteria, as well as to the opportunistic yeast Candida albicans.

With the increasing use of invasive, interventional, indwelling, and implanted medical devices, healthcare-associated infections caused by pathogenic biofilms have become a major cause of morbidity and mortality. Herein, we present the fabrication, characterization, and in vitro evaluation of biocompatibility and anti-biofilm properties of new coatings based on Fe 3 O 4 nanoparticles (NPs) loaded with usnic acid (UA) and ceftriaxone (CEF). Sodium lauryl sulfate (SLS) was employed as a stabilizer and modulator of the polarity, dispersibility, shape, and anti-biofilm properties of the magnetite nanoparticles. The resulting Fe 3 O 4 functionalized NPs, namely Fe 3 O 4 @SLS, Fe 3 O 4 @SLS/UA, and Fe 3 O 4 @SLS/CEF, respectively, were prepared by co-precipitation method and fully characterized by XRD, TEM, SAED, SEM, FTIR, and TGA. They were further used to produce nanostructured coatings by matrix-assisted pulsed laser evaporation (MAPLE) technique. The biocompatibility of the coatings was assessed by measuring the cell viability, lactate dehydrogenase release, and nitric oxide level in the culture medium and by evaluating the actin cytoskeleton morphology of murine pre-osteoblasts. All prepared nanostructured coatings exhibited good biocompatibility. Biofilm growth inhibition ability was tested at 24 h and 48 h against Staphylococcus aureus and Pseudomonas aeruginosa as representative models for Gram-positive and Gram-negative bacteria. The coatings demonstrated good biocompatibility, promoting osteoblast adhesion, migration, and growth without significant impact on cell viability or morphology, highlighting their potential for developing safe and effective antibacterial surfaces.

Orthopedic screws are subjected to high mechanical stress, corrosive environment, and microbial colonization, which may cumulatively lead to implant failure and periprosthetic joint infections. To overcome these issues, this study has focused on modifying the surface chemistry and topography of screws utilized in knee intervention toward enhancing their mechanical and biological behaviors. Specifically, this study has explored the optimization of composite coatings made of polycaprolactone (PCL), graphene oxide (GO), and Meropenem (MRP) via the matrix-assisted pulsed laser evaporation (MAPLE) technique. The PCL∕GO∕MRP coatings aimed to upgrade the surfaces of the implantable fixation devices, offering superior antimicrobial properties, reduced biofilm formation, and better mechanical characteristics. Comprehensive physicochemical analyses, including Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and Raman microscopy, confirmed uniform deposition, efficient material transfer, and preservation of functional groups. The developed coatings displayed significant antibacterial activity against Staphylococcus aureus and Escherichia coli, with a marked reduction in biofilm formation compared to uncoated surfaces. Thus, this work highlights the potential of the designed PCL∕GO∕MRP coatings as a strategy to enhance the biocompatibility and longevity of orthopedic screws, minimize complications related to implant-associated infections in knee surgeries, and ultimately improve post-surgical outcomes to increase patients' quality of life., Competing Interests: The authors declare that they have no conflict of interests.

The bioactive surface modification of implantable devices paves the way towards the personalized healthcare practice by providing a versatile and tunable approach that increase the patient outcome, facilitate the medical procedure, and reduce the indirect or secondary effects. The purpose of our study was to assess the performance of composite coatings based on biopolymeric spheres of poly(lactide-co-glycolide) embedded with hydroxyapatite (HA) and methotrexate (MTX). Bio-simulated tests performed for up to one week evidenced the gradual release of the antitumor drug and the biomineralization potential of PLGA/HA-MTX sphere coatings. The composite materials proved superior biocompatibility and promoted enhanced cell adhesion and proliferation with respect to human preosteoblast and osteosarcoma cell lines when compared to pristine titanium.

To modulate the bioactivity and boost the therapeutic outcome of implantable metallic devices, biodegradable coatings based on polylactide (PLA) and graphene oxide nanosheets (nGOs) loaded with Zinforo™ (Zin) have been proposed in this study as innovative alternatives for the local management of biofilm-associated periprosthetic infections. Using a modified Hummers protocol, high-purity and ultra-thin nGOs have been obtained, as evidenced by X-ray diffraction (XRD) and transmission electron microscopy (TEM) investigations. The matrix-assisted pulsed laser evaporation (MAPLE) technique has been successfully employed to obtain the PLA-nGO-Zin coatings. The stoichiometric and uniform transfer was revealed by infrared microscopy (IRM) and scanning electron microscopy (SEM) studies. In vitro evaluation, performed on fresh blood samples, has shown the excellent hemocompatibility of PLA-nGO-Zin-coated samples (with a hemolytic index of 1.15%), together with their anti-inflammatory ability. Moreover, the PLA-nGO-Zin coatings significantly inhibited the development of mature bacterial biofilms, inducing important anti-biofilm efficiency in the as-coated samples. The herein-reported results evidence the promising potential of PLA-nGO-Zin coatings to be used for the biocompatible and antimicrobial surface modification of metallic implants.

Recently, the favorable electrical properties of biomaterials have been acknowledged as crucial for various medical applications, including both bone healing and growth processes. This review will specifically concentrate on calcium phosphate (CaP)-based bioceramics, with a notable emphasis on hydroxyapatite (HA), among the diverse range of synthetic biomaterials. HA is currently the subject of extensive research in the medical field, particularly in dentistry and orthopedics. The existing literature encompasses numerous studies exploring the physical-chemical, mechanical, and biological properties of HA-based materials produced in various forms (i.e., powders, pellets, and/or thin films) using various physical and chemical vapor deposition techniques. In comparison, there is a relative scarcity of research on the electrical and dielectric properties of HA, which have been demonstrated to be essential for understanding dipole polarization and surface charge. It is noteworthy that these electrical and dielectric properties also offer valuable insights into the structure and functioning of biological tissues and cells. In this respect, electrical impedance studies on living tissues have been performed to assess the condition of cell membranes and estimate cell shape and size. The need to fill the gap and correlate the physical-chemical, mechanical, and biological characteristics with the electrical and dielectric properties could represent a step forward in providing new avenues for the development of the next-generation of high-performance HA-doped biomaterials for future top medical applications. Therefore, this review focuses on the electrical and dielectric properties of HA-based biomaterials, covering a range from powders and pellets to thin films, with a particular emphasis on the impact of the various dopants used. Therefore, it will be revealed that each dopant possesses unique properties capable of enhancing the overall characteristics of the produced structures. Considering that the electrical and dielectric properties of HA-based biomaterials have not been extensively explored thus far, the aim of this review is to compile and thoroughly discuss the latest research findings in the field, with special attention given to biomedical applications.

Exploring silver-based and carbon-based nanomaterials' excellent intrinsic antipathogenic effects represents an attractive alternative for fabricating anti-infective formulations. Using chemical synthesis protocols, stearate-conjugated silver (Ag@C 18 ) nanoparticles and graphene oxide nanosheets (nGOs) were herein obtained and investigated in terms of composition and microstructure. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) characterizations revealed the formation of nanomaterials with desirable physical properties, while X-ray diffraction (XRD) analyses confirmed the high purity of synthesized nanomaterials. Further, laser-processed Ag@C 18 -nGO coatings were developed, optimized, and evaluated in terms of biological and microbiological outcomes. The highly biocompatible Ag@C 18 -nGO nanostructured coatings proved suitable candidates for the local modulation of biofilm-associated periprosthetic infections.

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.

We report on a comparative in vitro study of selective cytotoxicity against MCF7 tumor cells and normal VERO cells tested on silver-based nanocoatings synthesized by the matrix-assisted pulsed laser evaporation (MAPLE) technique. Silver nanoparticles (AgNPs) were loaded with five representative cytostatic drugs (i.e., doxorubicin, fludarabine, paclitaxel, gemcitabine, and carboplatin) and with five essential oils (EOs) (i.e., oregano, rosemary, ginger, basil, and thyme). The as-obtained coatings were characterized by X-ray diffraction, thermogravimetry coupled with differential scanning calorimetry, Fourier-transform IR spectroscopy, IR mapping, and scanning electron microscopy. A screening of the impact of the prepared nanocoatings on the MCF7 tumor and normal VERO cell lines was achieved by means of cell viability MTT and cytotoxicity LDH assays. While all nanocoatings loaded with antitumor drugs exhibited powerful cytotoxic activity against both the tumor and the normal cells, those embedded with AgNPs loaded with rosemary and thyme EOs showed remarkable and statistically significant selective cytotoxicity against the tested cancercells. The EO-loaded nanocoatings were tested for antimicrobial and antibiofilm activity against Staphylococcus aureus , Escherichia coli , and Candida albicans . For all studied pathogens, the cell viability, assessed by counting the colony-forming units after 2 and 24 h, was significantly decreased by all EO-based nanocoatings, while the best antibiofilm activity was evidenced by the nanocoatings containing ginger and thyme EOs.

Novel biomaterials with promising bone regeneration potential, derived from rich, renewable, and cheap sources, are reported. Thus, thin films were synthesized from marine-derived (i.e., from fish bones and seashells) hydroxyapatite (MdHA) by pulsed laser deposition (PLD) technique. Besides the physical-chemical and mechanical investigations, the deposited thin films were also evaluated in vitro using dedicated cytocompatibility and antimicrobial assays. The morphological examination of MdHA films revealed the fabrication of rough surfaces, which were shown to favor good cell adhesion, and furthermore could foster the in-situ anchorage of implants. The strong hydrophilic behavior of the thin films was evidenced by contact angle (CA) measurements, with values in the range of 15-18°. The inferred bonding strength adherence values were superior (i.e., ~49 MPa) to the threshold established by ISO regulation for high-load implant coatings. After immersion in biological fluids, the growth of an apatite-based layer was noted, which indicated the good mineralization capacity of the MdHA films. All PLD films exhibited low cytotoxicity on osteoblast, fibroblast, and epithelial cells. Moreover, a persistent protective effect against bacterial and fungal colonization (i.e., 1- to 3-log reduction of E. coli , E. faecalis, and C. albicans growth) was demonstrated after 48 h of incubation, with respect to the Ti control. The good cytocompatibility and effective antimicrobial activity, along with the reduced fabrication costs from sustainable sources (available in large quantities), should, therefore, recommend the MdHA materials proposed herein as innovative and viable solutions for the development of novel coatings for metallic dental implants.

As the clinical complications induced by microbial infections are known to have life-threatening side effects, conventional anti-infective therapy is necessary, but not sufficient to overcome these issues. Some of their limitations are connected to drug-related inefficiency or resistance and pathogen-related adaptive modifications. Therefore, there is an urgent need for advanced antimicrobials and antimicrobial devices. A challenging, yet successful route has been the development of new biostatic or biocide agents and biomaterials by considering the indisputable advantages of biopolymers. Polymers are attractive materials due to their physical and chemical properties, such as compositional and structural versatility, tunable reactivity, solubility and degradability, and mechanical and chemical tunability, together with their intrinsic biocompatibility and bioactivity, thus enabling the fabrication of effective pharmacologically active antimicrobial formulations. Besides representing protective or potentiating carriers for conventional drugs, biopolymers possess an impressive ability for conjugation or functionalization. These aspects are key for avoiding malicious side effects or providing targeted and triggered drug delivery (specific and selective cellular targeting), and generally to define their pharmacological efficacy. Moreover, biopolymers can be processed in different forms (particles, fibers, films, membranes, or scaffolds), which prove excellent candidates for modern anti-infective applications. This review contains an overview of antimicrobial polyester-based formulations, centered around the effect of the dimensionality over the properties of the material and the effect of the production route or post-processing actions.

In this study, we report the performance improvement of wound dressings by covering them with magnetite-based nanostructured coatings. The magnetite nanoparticles (Fe 3 O 4 NPs) were functionalized with Nigella sativa ( N. sativa ) powder/essential oil and dicloxacillin and were synthesized as coatings by matrix assisted pulsed laser evaporation (MAPLE). The expected effects of this combination of materials are: (i) to reduce microbial contamination, and (ii) to promote rapid wound healing. The crystalline nature of core/shell Fe 3 O 4 NPs and coatings was determined by X-ray diffraction (XRD). Differential Scanning Calorimetry (DSC) and Thermo Gravimetric Analysis (TGA) have been coupled to investigate the stability and thermal degradation of core/shell nanoparticle components. The coatings' morphology was examined by scanning electron microscopy (SEM). The distribution of chemical elements and functional groups in the resulting coatings was evidenced by Fourier transform infrared (FTIR) spectrometry. In order to simulate the interaction between wound dressings and epithelial tissues and to evaluate the drug release in time, the samples were immersed in simulated body fluid (SBF) and investigated after different durations of time. The antimicrobial effect was evaluated in planktonic (free-floating) and attached (biofilms) bacteria models. The biocompatibility and regenerative properties of the nanostructured coatings were evaluated in vitro , at cellular, biochemical, and the molecular level. The obtained results show that magnetite-based nanostructured coatings functionalized with N. sativa and dicloxacillin are biocompatible and show an enhanced antimicrobial effect against Gram positive and Gram negative opportunistic bacteria.

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 (SiO 2 )-coated magnetite (Fe 3 O 4 )-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 Fe 3 O 4 NPs can improve the antimicrobial activity of E, while the use of a SiO 2 matrix may increase its efficiency over prolonged periods of time. The Fe 3 O 4 @SiO 2 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.

In this study, we used the matrix-assisted pulsed laser evaporation (MAPLE) technique to obtain hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ) and magnesium phosphate (Mg 3 (PO 4 ) 2 ) thin coatings containing bone morphogenetic protein (BMP4) for promoting implants osteointegration and further nebulized with the antibiotic ceftriaxone (CXF) to prevent peri-implant infections. The samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED), infrared microscopy (IRM) and Fourier-transform infrared spectroscopy (FT-IR). Furthermore, the antimicrobial properties were evaluated on Staphylococcus aureus biofilms and the cytocompatibility on the MC3T3-E1 cell line. The obtained results proved the potential of the obtained coatings for bone implant applications, providing a significant antimicrobial and antibiofilm effect, especially in the first 48 h, and cytocompatibility in relation to murine osteoblast cells., Competing Interests: The authors declare no conflict of interest.

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.

Bone disorders and traumas represent a common type of healthcare emergency affecting men and women worldwide. Since most of these diseases imply surgery, frequently complicated by exogenous or endogenous infections, there is an acute need for improving their therapeutic approaches, particularly in clinical conditions requiring orthopedic implants. Various biomaterials have been investigated in the last decades for their potential to increase bone regeneration and prevent orthopedic infections. The present study aimed to develop a series of MAPLE-deposited coatings composed of magnesium phosphate (Mg 3 (PO 4 ) 2 ) and silver nanoparticles (AgNPs) designed to ensure osteoblast proliferation and anti-infective properties simultaneously. Mg 3 (PO 4 ) 2 and AgNPs were obtained through the cooling bath reaction and chemical reduction, respectively, and then characterized through X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), and Selected Area Electron Diffraction (SAED). Subsequently, the obtained coatings were evaluated by Infrared Microscopy (IRM), Fourier-Transform Infrared Spectroscopy (FT-IR), and Scanning Electron Microscopy (SEM). Their biological properties show that the proposed composite coatings exhibit well-balanced biocompatibility and antibacterial activity, promoting osteoblasts viability and proliferation and inhibiting the adherence and growth of Staphylococcus aureus and Pseudomonas aeruginosa, two of the most important agents of orthopedic implant-associated infections.

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.

In the context of inefficient antibiotics, antibacterial alternatives are urgently needed to stop the increasing resistance rates in pathogens. This study reports the fabrication and characterization of four promising magnetite-based antibiotic delivery systems for ENT (ear, nose and throat) applications. Magnetite nanoparticles were functionalized with streptomycin and neomycin and some were entrapped in polymeric spheres. The obtained nanomaterials are stable, with spherical morphology, their size ranging from ~2.8 to ~4.7 nm for antibiotic-coated magnetite nanoparticles, and from submicron sizes up to several microns for polymer-coated magnetite-antibiotic composites. Cell viability and antimicrobial tests demonstrated their biocompatibility on human diploid cells and their antibacterial effect against Gram-negative ( Pseudomonas aeruginosa ) and Gram-positive ( Staphylococcus aureus ) opportunistic bacteria. The presence of the polymeric coat proved an enhancement in biocompatibility and a slight reduction in the antimicrobial efficiency of the spheres. Our results support the idea that functional NPs and polymeric microsystems containing functional NPs could be tailored to achieve more biocompatibility or more antimicrobial effect, depending on the bioactive compounds they incorporate and their intended application.

This study reports the fabrication of nanostructured coatings based on magnetite, polyethyleneglycol, and biologically active molecule (polymyxin B-PM) for producing biofilm-resistant surfaces (voice prosthesis). Magnetite nanoparticles (MNPs) have been synthesized and functionalized using a co-precipitation method and were further deposited into thin coatings using the matrix-assisted pulsed laser evaporation (MAPLE) technique. The obtained nanoparticles and coatings were characterized by X-ray diffraction (XRD), thermogravimetric analysis with differential scanning calorimetry (TGA-DSC), scanning electron microscopy (SEM), transmission electron microscopy with selected area electron diffraction (TEM-SAED), Fourier-transform infrared spectroscopy (FT-IR), and infrared microscopy (IRM). Their antibiofilm activity was tested against relevant Staphylococcus aureus and Pseudomonas aeruginosa bacterial strains. The Fe 3 O 4 @PEG/PM surface of modified voice prosthesis sections reduced the number of CFU/mL up to four orders of magnitude in the case of S. aureus biofilm. A more significant inhibitory effect is noticed in the case of P. aeruginosa up to five folds. These results highlight the importance of new Fe 3 O 4 @PEG/PM in the biomedical field.

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.

This review summarizes the results reported on the production of biphasic calcium phosphate (BCP) materials derived from fish wastes (i.e., heads, bones, skins, and viscera), known as fish discards, and offers an in-depth discussion on their promising potential for various applications in many fields, especially the biomedical one. Thus, considerable scientific and technological efforts were recently focused on the capability of these sustainable materials to be transformed into economically attractive and highly valuable by-products. As a consequence of using these wastes, plenty of beneficial social effects, with both economic and environmental impact, will arise. In the biomedical field, there is a strong and continuous interest for the development of innovative solutions for healthcare improvement using alternative materials of biogenic origin. Thus, the orthopedic field has witnessed a significant development due to an increased demand for a large variety of implants, grafts, and/or scaffolds. This is mainly due to the increase of life expectancy and higher frequency of bone-associated injuries and diseases. As a consequence, the domain of bone-tissue engineering has expanded to be able to address a plethora of bone-related traumas and to deliver a viable and efficient substitute to allografts or autografts by combining bioactive materials and cells for bone-tissue ingrowth. Among biomaterials, calcium phosphate (CaP)-based bio-ceramics are widely used in medicine, in particular in orthopedics and dentistry, due to their excellent bioactive, osteoconductive, and osteointegrative characteristics. Recently, BCP materials (synthetic or natural), a class of CaP, which consist of a mixture of two phases, hydroxyapatite (HA) and beta tricalcium phosphate (β-TCP), in different concentrations, gained increased attention due to their superior overall performances as compared to single-phase formulations. Moreover, the exploitation of BCP materials from by-products of fish industry was reported to be a safe, cheap, and simple procedure. In the dedicated literature, there are many reviews on synthetic HA, β-TCP, or BCP materials, but to the best of our knowledge, this is the first collection of results on the effects of processing conditions on the morphological, compositional, structural, mechanical, and biological properties of the fish discard-derived BCPs along with the tailoring of their features for various applications.

Biofilms represent a common and increasingly challenging problem in healthcare practices worldwide, producing persistent and difficult to manage infections. Researchers have started developing antibiotic-free treatment alternatives in order to decrease the risk of resistant microbial strain selection and for the efficient management of antibiotic tolerant biofilm infections. The present study reports the fabrication and characterization of magnetite-based nanostructured coatings for producing biofilm-resistant surfaces. Specifically, magnetite nanoparticles (Fe 3 O 4 ) were functionalized with chitosan (CS) and were blended with lysozyme (LyZ) and were deposited using the matrix-assisted pulsed laser evaporation (MAPLE) technique. A variety of characterization techniques were employed to investigate the physicochemical properties of both nanoparticles and nanocoatings. The biological characterization of the coatings assessed through cell viability and antimicrobial tests showed biocompatibility on osteoblasts as well as antiadhesive and antibiofilm activity against both Gram-negative and Gram-positive bacterial strains and no cytotoxic effect against human-cultured diploid cells.

Biofilms represent an increasing challenge in the medical practice worldwide, imposing a serious threat to public health. As bacterial strains have developed antibiotic resistance, researcher's attention has been extensively focused on developing more efficient antimicrobial strategies. In this context, the present study reports the synthesis, physicochemical characterization, ex vivo biodistribution, and in vitro evaluation of the capacity of nanostructured surfaces based on zinc oxide (ZnO) and biologically active molecules to modulate clinically relevant microbial biofilms. ZnO nanoparticles (NPs) were synthesized through a co-precipitation method without thermal treatment. The matrix-assisted pulsed laser evaporation (MAPLE) was applied for preparing nanostructured coatings based on ZnO NPs surface modified with linalool that were further characterized by X-ray diffraction (XRD), thermogravimetric analysis with differential scanning calorimetry (TGA-DSC), scanning electron microscopy (SEM), transmission electron microscopy with selected area electron diffraction (TEM-SAED), Fourier-transform infrared spectroscopy (FT-IR), and infrared microscopy (IRM). Histological analyses carried out at 7 days and 14 days after the intraperitoneal administration of linalool modified ZnO NPs revealed the absence of the latter from the brain, kidney, liver, lung, myocardium, and pancreas. Through in vitro assays on prokaryotic cells, it was proven that ZnO coatings hinder microbial biofilm formation of both Gram-positive and Gram-negative bacteria strains.

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 (Fe 3 O 4 ) nanoparticles' surface modified with β-cyclodextrin (CD) and paclitaxel (PTX)-guest-host inclusion complexes (Fe 3 O 4 @β-CD/PTX). Both pristine Fe 3 O 4 @β-CD nanopowders and PTX-loaded thin films fabricated by MAPLE technique were investigated. Pristine Fe 3 O 4 @β-CD and Fe 3 O 4 @β-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, Fe 3 O 4 @β-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.

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.

Although bone possesses a remarkable capacity for self-remodeling and self-healing of small defects, the continuously increasing growth of bone diseases in the elderly population is becoming a significant burden, affecting individual life quality and society. Conventional treatment options involve surgical procedures for repair and reconstruction, local debridement, autografts or allografts, bone transport, Masquelet's two-stage reconstructions, and vascularized bone transplants. However, as such approaches often lead to disruptions of bone-regeneration processes and microbial contaminations and are often inefficient, researchers focus on developing bone-regenerative strategies and identifying novel therapeutic agents that could aid the bone-healing process. In this regard, plant-derived biocompounds, especially essential oils (EOs), have received great scientific attention in recent years, owing to their antioxidant, anti-inflammatory, and antimicrobial effects. Current studies focus on either the direct application of EOs on bone tissue or the introduction of EOs as bioactive compounds in bone scaffolds or as coatings for bone implants. Some of the EOs investigated involve St. John's wort, rosemary, thyme, ylang, white poplar, eucalyptus, lavender, and grape seed. In this context, the present paper aims to provide an overview of the main mechanisms involved in bone repair and regeneration and the potential of EOs to address and enhance these mechanisms.

The present study reports on the development and evaluation of nanostructured composite coatings of polylactic acid (PLA) embedded with iron oxide nanoparticles (Fe 3 O 4 ) modified with Eucalyptus ( Eucalyptus globulus ) essential oil. The co-precipitation method was employed to synthesize the magnetite particles conjugated with Eucalyptus natural antibiotic (Fe 3 O 4 @EG), while their composition and microstructure were investigated using grazing incidence X-ray diffraction (GIXRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The matrix-assisted pulsed laser evaporation (MAPLE) technique was further employed to obtain PLA/Fe 3 O 4 @EG thin films. Optimal experimental conditions for laser processing were established by complementary infrared microscopy (IRM) and scanning electron microscopy (SEM) investigations. The in vitro biocompatibility with eukaryote cells was proven using mesenchymal stem cells, while the anti-biofilm efficiency of composite PLA/Fe 3 O 4 @EG coatings was assessed against Gram-negative and Gram-positive pathogens.

Natural-derived biopolymers are suitable candidates for developing specific and selective performance-enhanced antimicrobial formulations. Composite polymeric particles based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and chitosan, P(3HB-3HV)-CS, are herein proposed as biocompatible and biodegradable delivery systems for bioproduced antibiotics: bacitracin (Bac), neomycin (Neo) and kanamycin (Kan). The stimuli-responsive spheres proved efficient platforms for boosting the antibiotic efficiency and antibacterial susceptibility, as evidenced against Gram-positive and Gram-negative strains. Absent or reduced proinflammatory effects were evidenced on macrophages in the case of Bac-/Neo- and Kan-loaded spheres, respectively. Moreover, these systems showed superior ability to sustain and promote the proliferation of dermal fibroblasts, as well as to preserve their ultrastructure (membrane and cytoskeleton integrity) and to exhibit anti-oxidant activity. The antibiotic-loaded P(3HB-3HV)-CS spheres proved efficient alternatives for antibacterial strategies.

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.

Due to their excellent mechanical and biocompatibility properties, titanium-based implants are successfully used as biomedical devices. However, when new bone formation fails for different reasons, impaired fracture healing becomes a clinical problem and affects the patient's quality of life. We aimed to design a new bioactive surface of titanium implants with a synergetic PEG biopolymer-based composition for gradual delivery of growth factors (FGF2, VEGF, and BMP4) during bone healing. The optimal architecture of non-cytotoxic polymeric coatings deposited by dip coating under controlled parameters was assessed both in cultured cells and in a rat tibial defect model (100% viability). Notably, the titanium adsorbed polymer matrix induced an improved healing process when compared with the individual action of each biomolecules. High-performance mass spectrometry analysis demonstrated that recovery after a traumatic event is governed by specific differentially regulated proteins, acting in a coordinated response to the external stimulus. Predicted protein interactions shown by STRING analysis were well organized in hub-based networks related with response to chemical, wound healing and response to stress pathways. The proposed functional polymer coatings of the titanium implants demonstrated the significant improvement of bone healing process after injury.

In order to overcome the shortcomings related to unspecific and partially efficient conventional wound dressings, impressive efforts are oriented in the development and evaluation of new and effective platforms for wound healing applications. In situ formed wound dressings provide several advantages, including proper adaptability for wound bed microstructure and architecture, facile application, patient compliance and enhanced therapeutic effects. Natural or synthetic, composite or hybrid biomaterials represent suitable candidates for accelerated wound healing, by providing proper air and water vapor permeability, structure for macro- and microcirculation, support for cellular migration and proliferation, protection against microbial invasion and external contamination. Besides being the most promising choice for wound care applications, polymeric biomaterials (either from natural or synthetic sources) may exhibit intrinsic wound healing properties. Several nanotechnology-derived biomaterials proved great potential for wound healing applications, including micro- and nanoparticulate systems, fibrous scaffolds, and hydrogels. The present paper comprises the most recent data on modern and performant strategies for effective wound healing.

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 (Fe 3 O 4 @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 Fe 3 O 4 @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 Fe 3 O 4 @AN showed significant cytotoxic activity against human adenocarcinoma HT-29 cells after prolonged exposure. Antimicrobial results demonstrated that Fe 3 O 4 @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.

Since Graphene discovery, their associated derivate nanomaterials, Graphene Oxide (GO) and reduced-GO were in the forefront of continuous developments in bio-nano-technology due to unique physical-chemical properties. Although GO nano-colloids (GON) were proposed as drug release matrix for targeting cancer cells, there is still a concern regarding its cytotoxicity issues. In this study, we report on the fabrication of functional GON bio-coatings by Matrix-Assisted Pulsed Laser Evaporation (MAPLE) to be used as drug carriers for targeting melanoma cells. We first performed a thorough in vitro cytotoxicity assay for comparison between GON and protein functionalized GON coatings. As functionalization protein, Bovine Serum Albumin (BSA) was non-covalently conjugated to GO surface. Safe concentration windows were identified in cytotoxicity tests by live/dead staining and MTS assays for five different human melanoma cell lines as well as for non-transformed melanocytes and human dermal fibroblasts. Hybrid GON-BSA nano-scaled thin coatings incorporating Dabrafenib (DAB) and Trichostatin A (TSA) inhibitors for cells bearing BRAF V600E pathway activating mutation were assembled on solid substrates by MAPLE technique. We further demonstrated the successful immobilization for each drug-containing GON-BSA assembling systems by evaluating cellular BRAF activity inhibition and histone deacetylases activity blocking, respectively. DAB activity was proven by the decreased ERK phosphorylation in primary melanoma cells (SKmel28 BRAF V600E cell line), while TSA effect was evidenced by acetylated histones accumulation in cell's nuclei (SKmel23 BRAF WT cell line). In addition, melanoma cells exposed to GON-BSA coatings with compositional gradient of inhibitors evidenced a dose-dependent effect on target activity. Such functional bio-platforms could present high potential for cell-biomaterial interface engineering to be applied in personalized cancer therapy studies., (Copyright © 2020 Sima, Chiritoiu, Negut, Grumezescu, Orobeti, Munteanu, Sima and Axente.)

Aseptic loosening and periprosthetic infections are the main causes of implant failure. Strategies to mitigate this drawback are therefore mandatory to avoid primary and revision replacement surgeries. A functional bioapatite-biopolymer double nanostructure fabricated by matrix-assisted pulsed laser evaporation to prevent infection of orthopedic and dental implants could promote osseointegration and ensure controlled delivery of natural antimicrobial drugs. The synthesized nanostructure consists of two overlapping layers, the lower from a biocompatible polymer for anticorrosive protection, and the upper of bioactive glass incorporating antimicrobial plant extract, acting as a potential drug delivery system. Morphology, composition, adherence, ability for drug delivery and biological properties (cytotoxicity and antimicrobial effect) were studied. Structures proved compact and stable, conserving a remarkable drug delivery ability for more than 21 days, i.e., enough to ensure long-term microbes' eradication.

Thanks to its peculiar interactions with biological molecules and structures, metallic silver in the form of silver nanoparticles achieved a remarkable comeback as a potential antimicrobial agent. The antimicrobial use of silver nanoparticles is of clinical importance, as several pathogenic microorganisms developed resistance against various conventional drug treatments. Hence, given the extensive efficiency of silver nanoparticles against drug-sensitive and drug-resistant pathogens, their therapeutic implications were demonstrated in multiple medical applications, such as silver-based dressings, silver-coated biomedical devices and silver-containing nanogels. Bacterial strains possess an intrinsic ability to form well-organized microbial communities, capable of developing adaptive mechanisms to environmental aggression and self-protective pathways against antibiotics. The formation of these mono- or poly-microbial colonies, called biofilms, is closely related with the occurrence of infectious processes which result in severe and chronic pathologies. Therefore, substantial efforts were oriented to the development of new protective coatings for biomedical surfaces, capable of sustaining the physiological processes within human-derived normal cells and to disrupt the microbial contamination and colonization stages. Nanostructured materials based on polylactic acid and silver nanoparticles are herein proposed as bioactive coatings able to prevent the formation of microbial biofilms on biomedical relevant surfaces.

We report on the synthesis and evaluation of biopolymeric spheres of poly(lactide-co-glycolide) containing different amounts of magnetite nanoparticles and Ibuprofen (PLGA-Fe 3 O 4 -IBUP), but also chitosan (PLGA-CS-Fe 3 O 4 -IBUP), to be considered as drug delivery systems. Besides morphological, structural, and compositional characterizations, the PLGA-Fe 3 O 4 -IBUP composite microspheres were subjected to drug release studies, performed both under biomimetically-simulated dynamic conditions and under external radiofrequency magnetic fields. The experimental data resulted by performing the drug release studies evidenced that PLGA-Fe 3 O 4 -IBUP microspheres with the lowest contents of Fe 3 O 4 nanoparticles are optimal candidates for triggered drug release under external stimulation related to hyperthermia effect. The as-selected microspheres and their chitosan-containing counterparts were biologically assessed on macrophage cultures, being evaluated as biocompatible and bioactive materials that are able to promote cellular adhesion and proliferation. The composite biopolymeric spheres resulted in inhibited microbial growth and biofilm formation, as assessed against Staphylococcus aureus , Pseudomonas aeruginosa, and Candida albicans microbial strains. Significantly improved antimicrobial effects were reported in the case of chitosan-containing biomaterials, regardless of the microorganisms' type. The nanostructured composite biopolymeric spheres evidenced proper characteristics as prolonged and controlled drug release platforms for multipurpose biomedical applications.

Mechanical, thermal, chemical, or ischemic injury of the central or peripheral nervous system results in neuron loss, neurite damage, and/or neuronal dysfunction, almost always accompanied by sensorimotor impairment which alters the patient's life quality. The regenerative strategies for the injured nervous system are currently limited and mainly allow partial functional recovery, so it is necessary to develop new and effective approaches for nervous tissue regenerative therapy. Nanomaterials based on inorganic or organic and composite or hybrid compounds with tunable physicochemical properties and functionality proved beneficial for the transport and delivery/release of various neuroregenerative-relevant biomolecules or cells. Within the following paragraphs, we will emphasize that nanomaterial-based strategies (including nanosized and nanostructured biomaterials) represent a promising alternative towards repairing and regenerating the injured nervous system.

The intricate microstructure of the blood-brain barrier (BBB) is responsible for the accurate intrinsic regulation of the central nervous system (CNS), in terms of neuronal pathophysiological phenomena. Any disruption to the BBB can be associated with genetic defects triggering or with local antigenic invasion (either neurotoxic blood-derived metabolites and residues or microbial pathogens). Such events can be further related to systemic inflammatory or immune disorders, which can subsequently initiate several neurodegenerative pathways. Any degenerative process related to the CNS results in progressive and yet incurable impairment of neuronal cells. Since these particular neurons are mostly scanty or incapable of self-repair and regeneration processes, there is tremendous worldwide interest in novel therapeutic strategies for such specific conditions. Alzheimer's and Parkinson's diseases (AD and PD, respectively) are conditions found worldwide, being considered the most rampant degenerative pathologies related to CNS. The current therapy of these conditions, including both clinical and experimental approaches, mainly enables symptom management and subsidiary neuronal protection and even less disease regression. Still, a thorough understanding of the BBB pathophysiology and an accurate molecular and sub-molecular management of AD and PD will provide beneficial support for more specific and selective therapy. Since nanotechnology-derived materials and devices proved attractive and efficient platforms for modern biomedicine (including detection, imaging, diagnosis, medication, restoration and regeneration), a particular approach for AD and PD management relies on nanoparticle-based therapy. In this paper we will discuss relevant aspects related to the BBB and its impact on drug-based treatment and emphasize that nanoparticles are suitable and versatile candidates for the development of novel and performance-enhanced nanopharmaceuticals for neurodegenerative conditions therapy.

Composite thin coatings of conductive polymer (polyaniline grafted lignin, PANI-LIG) embedded with aminoglycoside Gentamicin sulfate (GS) or magnetite nanoparticles loaded with GS (Fe₃O₄@GS) were deposited by the matrix-assisted pulsed laser evaporation (MAPLE) technique. The aim was to obtain such nanostructured coatings for titanium-based biomedical surfaces, which would induce multi-functional properties to implantable devices, such as the controlled release of the therapeutically active substance under the action of a magnetic and/or electric field. Thus, the unaltered laser transfer of the initial biomaterials was reported, and the deposited thin coatings exhibited an appropriate nanostructured surface, suitable for bone-related applications. The laser processing of PANI-LIG materials had a meaningful impact on the composites' wettability, since the contact angle values corresponding to the composite laser processed materials decreased in comparison with pristine conductive polymer coatings, indicating more hydrophilic surfaces. The corrosion resistant structures exhibited significant antimicrobial activity against Escherichia coli , Staphylococcus aureus , and Candida albicans strains. In vitro cytotoxicity studies demonstrated that the PANI-LIG-modified titanium substrates can allow growth of bone-like cells. These results encourage further assessment of this type of biomaterial for their application in controlled drug release at implantation sites by external activation.

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.

The aim of our study was to obtain and evaluate the properties of polymeric coatings based on poly(lactic-co-glycolic) acid (PLGA) embedded with magnetite nanoparticles functionalized with commercial antimicrobial drugs. In this respect, we firstly synthesized the iron oxide particles functionalized (@) with the antibiotic Cefepime (Fe₃O₄@CEF). In terms of composition and microstructure, the as-obtained powdery sample was investigated by means of grazing incidence X-ray diffraction (GIXRD), thermogravimetric analysis (TGA), scanning and transmission electron microscopy (SEM and TEM, respectively). Crystalline and nanosized particles (~5 nm mean particle size) with spherical morphology, consisting in magnetite core and coated with a uniform and reduced amount of antibiotic shell, were thus obtained. In vivo biodistribution studies revealed the obtained nanoparticles have a very low affinity for innate immune-related vital organs. Composite uniform and thin coatings based on poly(lactide-co-glycolide) (PLGA) and antibiotic-functionalized magnetite nanoparticles (PLGA/Fe₃O₄@CEF) were subsequently obtained by using the matrix assisted pulsed laser evaporation (MAPLE) technique. Relevant compositional and structural features regarding the composite coatings were obtained by performing infrared microscopy (IRM) and SEM investigations. The efficiency of the biocompatible composite coatings against biofilm development was assessed for both Gram-negative and Gram-positive pathogens. The PLGA/Fe₃O₄@CEF materials proved significant and sustained anti-biofilm activity against staphylococcal and Escherichia coli colonisation.

The purpose of this study was to obtain, characterize and evaluate the cytotoxicity and antimicrobial activity of coatings based on poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) - Lysozyme (P(3HB-3HV)/Lys) and P(3HB-3HV) - Polyethylene glycol - Lysozyme (P(3HB-3HV)/PEG/Lys) spheres prepared by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique, in order to obtain functional and improved Ti-based implants. Morphological investigation of the coatings by Infrared Microscopy (IRM) and SEM revealed that the average diameter of P(3HB-3HV)/Lys spheres is around 2μm and unlike the drop cast samples, IRM recorded on MAPLE films revealed a good distribution of monitored functional groups on the entire scanned surface. The biological evaluation of MAPLE structured surfaces revealed an improved biocompatibility with respect to osteoblasts and endothelial cells as compared with Ti substrates and an enhanced anti-biofilm effect against Gram positive (Staphylococcus aureus) and Gram negative (Pseudomonas aeruginosa) tested strains. Thus, we propose that the fabricated P(3HB-3HV)/PEG/Lys and P(3HB-3HV)/Lys microspheres may be efficiently used as a matrix for controlled local drug delivery, with practical applications in developing improved medical surfaces for the reduction of implant-associated infections., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Deposition of bioactive coatings composed of zinc oxide, cyclodextrin and cefepime (ZnO/CD/Cfp) was performed by the Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The obtained nanostructures were characterized by X-ray diffraction, IR microscopy and scanning electron microscopy. The efficient release of cefepime was correlated with an increased anti-biofilm activity of ZnO/CD/Cfp composites. In vitro and in vivo tests have revealed a good biocompatibility of ZnO/CD/Cfp coatings, which recommend them as competitive candidates for the development of antimicrobial surfaces with biomedical applications. The release of the fourth generation cephalosporin Cfp in a biologically active form from the ZnO matrix could help preventing the bacterial adhesion and the subsequent colonization and biofilm development on various surfaces, and thus decreasing the risk of biofilm-related infections.

Due to their persistence and resistance to the current therapeutic approaches, Staphylococcus aureus biofilm-associated infections represent a major cause of morbidity and mortality in the hospital environment. Since (+)-usnic acid (UA), a secondary lichen metabolite, possesses antimicrobial activity against Gram-positive cocci, including S. aureus, the aim of this study was to load magnetic polylactic-co-glycolic acid-polyvinyl alcohol (PLGA-PVA) microspheres with UA, then to obtain thin coatings using matrix-assisted pulsed laser evaporation and to quantitatively assess the capacity of the bio-nano-active modified surface to control biofilm formation by S. aureus, using a culture-based assay. The UA-loaded microspheres inhibited both the initial attachment of S. aureus to the coated surfaces, as well as the development of mature biofilms. In vitro bioevalution tests performed on the fabricated thin films revealed great biocompatibility, which may endorse them as competitive candidates for the development of improved non-toxic surfaces resistant to S. aureus colonization and as scaffolds for stem cell cultivation and tissue engineering.

Novel derivatives were prepared by reaction of aromatic amines with 2-(4-ethylphenoxymethyl)benzoyl isothiocyanate, affording the N-[2-(4-ethylphenoxymethyl) benzoyl]-Nꞌ-(substituted phenyl)thiourea. Structural elucidation of these compounds was performed by IR, NMR spectroscopy and elemental analysis. The new compounds were used in combination with Fe3O4 and polyvinylpyrrolidone (PVP) for the coating of medical surfaces. In our experiments, catheter pieces were coated by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The microbial adherence ability was investigated in 6 multi-well plates by using culture based methods. The obtained surfaces were also assessed for their cytotoxicity with respect to osteoblast cells, by using fluorescence microscopy and MTT assay. The prepared surfaces by advanced laser processing inhibited the adherence and biofilm development ability of Staphylococcus aureus and Pseudomonas aeruginosa tested strains while cytotoxic effects on the 3T3-E1 preosteoblasts embedded in layer shaped alginate hydrogels were not observed. These results suggest that the obtained medical surfaces, based on the novel thiourea derivatives and magnetic nanoparticles with a polymeric shell could represent a promising alternative for the development of new and effective anti-infective strategies.

Cinnamomum verum-functionalized Fe3O4 nanoparticles of 9.4 nm in size were laser transferred by matrix assisted pulsed laser evaporation (MAPLE) technique onto gastrostomy tubes (G-tubes) for antibacterial activity evaluation toward Gram positive and Gram negative microbial colonization. X-ray diffraction analysis of the nanoparticle powder showed a polycrystalline magnetite structure, whereas infrared mapping confirmed the integrity of C. verum (CV) functional groups after the laser transfer. The specific topography of the deposited films involved a uniform thin coating together with several aggregates of bio-functionalized magnetite particles covering the G-tubes. Cytotoxicity assays showed an increase of the G-tube surface biocompatibility after Fe3O4@CV treatment, allowing a normal development of endothelial cells up to five days of incubation. Microbiological assays on nanoparticle-modified G-tube surfaces have proved an improvement of anti-adherent properties, significantly reducing both Gram negative and Gram positive bacteria colonization.

We report on the fabrication of thin coatings based on polylactic acid-chitosan-magnetite-eugenol (PLA-CS-Fe3O4@EUG) nanospheres by matrix assisted pulsed laser evaporation (MAPLE). Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) investigation proved that the homogenous Fe3O4@EUG nanoparticles have an average diameter of about 7 nm, while the PLA-CS-Fe3O4@EUG nanospheres diameter sizes range between 20 and 80 nm. These MAPLE-deposited coatings acted as bioactive nanosystems and exhibited a great antimicrobial effect by impairing the adherence and biofilm formation of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) bacteria strains. Moreover, the obtained nano-coatings showed a good biocompatibility and facilitated the normal development of human endothelial cells. These nanosystems may be used as efficient alternatives in treating and preventing bacterial infections.