Infection-Free and Enhanced Wound Healing Potential of Alginate Gels Incorporating Silver and Tannylated Calcium Peroxide Nanoparticles.

The treatment of chronic wounds involves precise requirements and complex challenges, as the healing process cannot go beyond the inflammatory phase, therefore increasing the healing time and implying a higher risk of opportunistic infection. Following a better understanding of the healing process, oxygen supply has been validated as a therapeutic approach to improve and speed up wound healing. Moreover, the local implications of antimicrobial agents (such as silver-based nano-compounds) significantly support the normal healing process, by combating bacterial contamination and colonization. In this study, silver (S) and tannylated calcium peroxide (CaO2@TA) nanoparticles were obtained by adapted microfluidic and precipitation synthesis methods, respectively. After complementary physicochemical evaluation, both types of nanoparticles were loaded in (Alg) alginate-based gels that were further evaluated as possible dressings for wound healing. The obtained composites showed a porous structure and uniform distribution of nanoparticles through the polymeric matrix (evidenced by spectrophotometric analysis and electron microscopy studies), together with a good swelling capacity. The as-proposed gel dressings exhibited a constant and suitable concentration of released oxygen, as shown for up to eight hours (UV-Vis investigation). The biofilm modulation data indicated a synergistic antimicrobial effect between silver and tannylated calcium peroxide nanoparticles, with a prominent inhibitory action against the Gram-positive bacterial biofilm after 48 h. Beneficial effects in the human keratinocytes cultured in contact with the obtained materials were demonstrated by the performed tests, such as MTT, LDH, and NO.

Nanostructured Coatings Based on Graphene Oxide for the Management of Periprosthetic Infections.

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.

Multifunctional Polymeric Biodegradable and Biocompatible Coatings Based on Silver Nanoparticles: A Comparative In Vitro Study on Their Cytotoxicity towards Cancer and Normal Cell Lines of Cytostatic Drugs versus Essential-Oil-Loaded Nanoparticles and on Their Antimicrobial and Antibiofilm Activities.

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.

Polymer Materials for Drug Delivery and Tissue Engineering.

In recent years, the biomedical engineering field has seen remarkable advancements, focusing mainly on developing novel solutions for enhancing tissue regeneration or improving therapeutic outcomes [...].

Silver/Graphene Oxide Nanostructured Coatings for Modulating the Microbial Susceptibility of Fixation Devices Used in Knee Surgery.

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@C18) 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@C18-nGO coatings were developed, optimized, and evaluated in terms of biological and microbiological outcomes. The highly biocompatible Ag@C18-nGO nanostructured coatings proved suitable candidates for the local modulation of biofilm-associated periprosthetic infections.

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.

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.

Magnetite-Based Nanostructured Coatings Functionalized with Nigella sativa and Dicloxacillin for Improved Wound Dressings.

In this study, we report the performance improvement of wound dressings by covering them with magnetite-based nanostructured coatings. The magnetite nanoparticles (Fe3O4 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 Fe3O4 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.

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.

In Vitro Interaction of Doxorubicin-Loaded Silk Sericin Nanocarriers with MCF-7 Breast Cancer Cells Leads to DNA Damage.

In this paper, Bombyx mori silk sericin nanocarriers with a very low size range were obtained by nanoprecipitation. Sericin nanoparticles were loaded with doxorubicin, and they were considered a promising tool for breast cancer therapy. The chemistry, structure, morphology, and size distribution of nanocarriers were investigated by Fourier transformed infrared spectroscopy (FTIR-ATR), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and dynamic light scattering (DLS). Morphological investigation and DLS showed the formation of sericin nanoparticles in the 25-40 nm range. FTIR chemical characterization showed specific interactions of protein-doxorubicin-enzymes with a high influence on the drug delivery process and release behavior. The biological investigation via breast cancer cell line revealed a high activity of nanocarriers in cancer cells by inducing significant DNA damage.

Current Landscape in Organic Nanosized Materials Advances for Improved Management of Colorectal Cancer Patients.

Globally, colorectal cancer (CRC) ranks as one of the most prevalent types of cancers at the moment, being the second cause of cancer-related deaths. The CRC chemotherapy backbone is represented by 5-fluorouracil, oxaliplatin, irinotecan, and their combinations, but their administration presents several serious disadvantages, such as poor bioavailability, lack of tumor specificity, and susceptibility to multidrug resistance. To address these limitations, nanomedicine has arisen as a powerful tool to improve current chemotherapy since nanosized carriers hold great promise in improving the stability and solubility of the drug payload and enhancing the active concentration of the drug that reaches the tumor tissue, increasing, therefore, the safety and efficacy of the treatment. In this context, the present review offers an overview of the most recent advances in the development of nanosized drug-delivery systems as smart therapeutic tools in CRC management and highlights the emerging need for improving the existing in vitro cancer models to reduce animal testing and increase the success of nanomedicine in clinical trials.

Bio- and Hemo-Compatible Silk Fibroin PEGylated Nanocarriers for 5-Fluorouracil Chemotherapy in Colorectal Cancer: In Vitro Studies.

5-fluorouracil (5-FU) remains the gold standard of treatment for colorectal cancer, but its poor bioavailability and high systemic toxicity highlight the urgent need for the development of novel delivery strategies to increase the efficacy of 5-FU treatment. The present study is aimed to design and validate a PEGylated Silk Fibroin Nanocarrier (SF/PEG nanoparticles (NPs)) as an efficient 5-FU delivery system for potential intravenous administration. Using the human adenocarcinoma HT-29 cell line as an in vitro model for colorectal cancer, the cytotoxicity screening of the SF/PEG NPs showed that pristine nanocarriers were highly biocompatible, while the addition of 5-FU triggers a dramatic reduction in tumor cell viability, proliferation potential and mitochondrial integrity as well as a significant increase in nitric oxide production. Despite their high in vitro cytotoxicity, the 5-FU SF/PEG NPs were found hemocompatible as no impact on red blood cells hemolysis or the phagocytic activity of the granulocytes was observed. Exposure of HT-29 tumor cells and blood samples to 5-FU SF/PEG NPs augmented the tumor necrosis factor-α levels. Moreover, 5-FU SF/PEG NPs showed an impact on tumor cell migration and invasive potential as both of these processes were inhibited by the NP treatment.

Composite P(3HB-3HV)-CS Spheres for Enhanced Antibiotic Efficiency.

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.

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.

Chemoprevention of Colorectal Cancer by Dietary Compounds.

Colorectal cancer is one of the leading causes of death, and the third most diagnosed type of cancer, worldwide. It is most common amongst men and women over 50 years old. Risk factors include smoking, alcohol, diet, physical inactivity, genetics, alterations in gut microbiota, and associated pathologies (diabetes, obesity, chronic inflammatory bowel diseases). This review will discuss, in detail, the chemopreventive properties of some dietary compounds (phenolic compounds, carotenoids, iridoids, nitrogen compounds, organosulfur compounds, phytosterols, essential oil compounds, polyunsaturated fatty acids and dietary fiber) against colorectal cancer. We present recent data, focusing on in vitro, laboratory animals and clinical trials with the previously mentioned compounds. The chemopreventive properties of the dietary compounds involve multiple molecular and biochemical mechanisms of action, such as inhibition of cell growth, inhibition of tumor initiation, inhibition of adhesion, migration and angiogenesis, apoptosis, interaction with gut microbiota, regulation of cellular signal transduction pathways and xenobiotic metabolizing enzymes, etc. Moreover, this review will also focus on the natural dietary compounds' bioavailability, their synergistic protective effect, as well as the association with conventional therapy. Dietary natural compounds play a major role in colorectal chemoprevention and continuous research in this field is needed.