Ultrasonic Coating of Poly(D,L-lactic acid)/Poly(lactic-co-glycolic acid) Electrospun Fibers with ZnO Nanoparticles to Increase Angiogenesis in the CAM Assay.

Critical-size bone defects necessitate bone void fillers that should be integrated well and be easily vascularized. One viable option is to use a biocompatible synthetic polymer and sonocoat it with zinc oxide (ZnO) nanoparticles (NPs). However, the ideal NP concentration and size must be assessed because a high dose of ZnO NPs may be toxic. Electrospun PDLLA/PLGA scaffolds were produced with different concentrations (0.5 or 1.0 s of sonocoating) and sizes of ZnO NPs (25 nm and 70 nm). They were characterized by SEM, EDX, ICP-OES, and the water contact angle. Vascularization and integration into the surrounding tissue were assessed with the CAM assay in the living chicken embryo. SEM, EDX, and ICP-OES confirmed the presence of ZnO NPs on polymer fibers. Sonocoated ZnO NPs lowered the WCA compared with the control. Smaller NPs were more pro-angiogenic exhibiting a higher vessel density than the larger NPs. At a lower concentration, less but larger vessels were visible in an environment with a lower cell density. Hence, the favored combination of smaller ZnO NPs at a lower concentration sonocoated on PDLLA/PLGA electrospun meshes leads to an advanced state of tissue integration and vascularization, providing a valuable synthetic bone graft to be used in clinics in the future.

Radiological properties of nano-hydroxyapatite compared to natural equine hydroxyapatite quantified using dual-energy CT and high-field MR.

In equine medicine, assisted bone regeneration, including use of biomaterial substitutes like hydroxyapatite (HAP), is crucial for addressing bone defects. To follow-up on the outcome of HAP-based bone defect treatment, the advancement in quantified diagnostic imaging protocols is needed. This study aimed to quantify and compare the radiological properties of the HAP graft and natural equine bone using Magnetic Resonance (MR) and Computed Tomography (CT), both Single (SECT) and Dual Energy (DECT). SECT and DECT, allow for the differentiation of three HAP grain sizes, by progressive increase in relative density (RD). SECT, DECT, and MR enable the differentiation between natural cortical bone and synthetic HAP graft by augmentation in Effective Z and material density (MD) in HAP/Water, Calcium/Water, and Water/Calcium reconstructions, alongside the reduction in T2 relaxation time. The proposed quantification provided valuable radiological insights into the composition of HAP grafts, which may be useful in follow-up bone defect treatment.

Lattice variation as a function of concentration and grain size in MgO-NiO solid solution system.

The study aimed to understand how changes in crystal's size affect the lattice parameters and crystal structure of Mg1-xNixO solid solution for six X values ranging from x = 0 to x = 1. Mg1-xNixO was synthesized via two different wet-chemical techniques: the sol-gel and the microwave hydrothermal method, both followed by calcination at different temperatures of 673, 873, 1073, 1273 and 1473 K. As annealing caused grain growth, the varied temperature range allowed to examine a wide range of grain sizes. The lattice parameters and x values were determined from XRD (X-ray diffraction) peak positions and intensities respectively. The grain size was evaluated by XRD line profile analysis and supported by SEM (scanning electron microscope) observations. At the temperatures of 673 and 873 K grain size was in the nanometric range and from 1073 K and above grain size was in the micrometric range. A non-monotonic lattice variation versus grain size was found for each concentration. When grain size decreased there was a slight contraction, however for grain size in the nanometric range there was a severe lattice expansion. Both lattice parameter changes were explained by two effects acting together: contraction due to surface stress and expansion due to weakening of the ionic bonding at nanocrystalline particles. In this current research study, the lattice parameter was mapped in two dimensions: concentration and grain size. The findings of this study provided valuable insights into the lattice variation in the MgO-NiO solid solution system.

Functionalized Carbon Nanotubes for Delivery of Ferulic Acid and Diosgenin Anticancer Natural Agents.

It was investigated whether loading multi-wall carbon nanotubes (CNTs) with two natural anticancer agents: ferulic acid (FUA) and diosgenin (DGN), may enhance the anticancer effect of these drugs. The CNTs were functionalized with carboxylic acid (CNTCOOH) or amine (CNTNH2), loaded with the above pro-drugs, as well as both combined and coated with chitosan or chitosan-stearic acid. Following physicochemical characterization, the drug-loading properties and kinetics of the drug's release were investigated. Their effects on normal human skin fibroblasts and MCF-7 breast carcinoma cells, HepG2 hepatocellular carcinoma cells, and A549 non-small-cell lung cancer cells were evaluated in vitro. Their actions at the molecular level were evaluated by assessing the expression of lncRNAs (HULC, HOTAIR, CCAT-2, H19, and HOTTIP), microRNAs (mir-21, mir-92, mir-145, and mir-181a), and proteins (TGF-ß and E-cadherin) in HepG2 cells. The release of both pro-drugs depended on the glutathione concentration, coating, and functionalization. Release occurred in two stages: a no-burst/zero-order release followed by a sustained release best fitted to Korsmeyer-Peppas kinetics. The combined nanoformulation cancer inhibition effect on HepG2 cancer cells was more pronounced than for A549 and MCF7 cells. The combined nanoformulations had an additive impact followed by a synergistic effect, with antagonism demonstrated at high concentrations. The nanoformulation coated with chitosan and stearic acid was particularly successful in targeting HepG2 cells and inducing apoptosis. The CNT functionalized with carboxylic acid (CNTCOOH), loaded with both FUA and DGN, and coated with chitosan-stearic acid inhibited the expression of lncRNAs and modulated both microRNAs and proteins. Thus, nanoformulations composed of functionalized CNTs dual-loaded with FUA and DGN and coated with chitosan-stearic acid are a promising drug delivery system that enhances the activity of natural pro-drugs.

Enhanced Release of Calcium Ions from Hydroxyapatite Nanoparticles with an Increase in Their Specific Surface Area.

Synthetic calcium phosphates, e.g., hydroxyapatite (HAP) and tricalcium phosphate (TCP), are the most commonly used bone-graft materials due to their high chemical similarity to the natural hydroxyapatite-the inorganic component of bones. Calcium in the form of a free ion or bound complexes plays a key role in many biological functions, including bone regeneration. This paper explores the possibility of increasing the Ca2+-ion release from HAP nanoparticles (NPs) by reducing their size. Hydroxyapatite nanoparticles were obtained through microwave hydrothermal synthesis. Particles with a specific surface area ranging from 51 m2/g to 240 m2/g and with sizes of 39, 29, 19, 11, 10, and 9 nm were used in the experiment. The structure of the nanomaterial was also studied by means of helium pycnometry, X-ray diffraction (XRD), and transmission-electron microscopy (TEM). The calcium-ion release into phosphate-buffered saline (PBS) was studied. The highest release of Ca2+ ions, i.e., 18 mg/L, was observed in HAP with a specific surface area 240 m2/g and an average nanoparticle size of 9 nm. A significant increase in Ca2+-ion release was also observed with specific surface areas of 183 m2/g and above, and with nanoparticle sizes of 11 nm and below. No substantial size dependence was observed for the larger particle sizes.

Co-Delivery System of Curcumin and Colchicine Using Functionalized Mesoporous Silica Nanoparticles Promotes Anticancer and Apoptosis Effects.

Purpose: Many natural agents have a high anticancer potential, and their combination may be advantageous for improved anticancer effects. Such agents, however, often are not water soluble and do not efficiently target cancer cells, and the kinetics of their action is poorly controlled. One way to overcome these barriers is to combine natural agents with nanoparticles. Our aim in the current study was to fabricate an anticancer nanoformulation for co-delivery of two natural agents, curcumin (CR) and colchicine (CL), with a core-shell structure. Using cancer cell lines, we compared the anticancer efficacy between the combination and a nanoformulation with CL alone. Methods: For the single-drug nanoformulation, we used phosphonate groups to functionalize mesoporous silica nanoparticles (MSNs) and loaded the MSNs with CL. Additional loading of this nanoformulation with CR achieved the co-delivery format. To create the structure with a core shell, we selected a chitosan−cellulose mixture conjugated with targeting ligands of folic acid for the coating. For evaluating anticancer and apoptosis effects, we assessed changes in important genes and proteins in apoptosis (p53, caspase-3, Bax, Bcl-2) in several cell lines (MCF-7, breast adenocarcinoma; HCT-116, colon carcinoma; HOS, human osteosarcoma; and A-549, non−small cell lung cancer). Results: Nanoformulations were successfully synthesized and contained 10.9 wt.% for the CL single-delivery version and 18.1 wt.% for the CL+CR co-delivery nanoformulation. Anticancer effects depended on treatment, cell line, and concentration. Co-delivery nanoformulations exerted anticancer effects that were significantly superior to those of single delivery or free CL or CR. Anticancer effects by cell line were in the order of HCT-116 > A549 > HOS > MCF-7. The lowest IC50 value was obtained for the nanoformulation consisting of CL and CR coated with a polymeric shell conjugated with FA (equivalent to 4.1 ± 0.05 µg/mL). With dual delivery compared with the free agents, we detected strongly increased p53, caspase-3, and Bax expression, but inhibition of Bcl-2, suggesting promotion of apoptosis. Conclusions: Our findings, although preliminary, indicate that the proposed dual delivery nanoformulation consisting of nanocore: MSNs loaded with CL and CR and coated with a shell of chitosan−cellulose conjugated folic acid exerted strong anticancer and apoptotic effects with potent antitumor activity against HCT-116 colon cells. The effect bested CL alone. Evaluating and confirming the efficacy of co-delivery nanoformulations will require in vivo studies.

Osteogenic Potential of Sheep Mesenchymal Stem Cells Preconditioned with BMP-2 and FGF-2 and Seeded on an nHAP-Coated PCL/HAP/ß-TCP Scaffold.

Mesenchymal stem cells (MSCs) attract interest in regenerative medicine for their potential application in bone regeneration. However, direct transplantation of cells into damaged tissue is not efficient enough to regenerate large bone defects. This problem could be solved with a biocompatible scaffold. Consequently, bone tissue engineering constructs based on biomaterial scaffolds, MSCs, and osteogenic cytokines are promising tools for bone regeneration. The aim of this study was to evaluate the effect of FGF-2 and BMP-2 on the osteogenic potential of ovine bone marrow-derived MSCs seeded onto an nHAP-coated PCL/HAP/ß-TCP scaffold in vitro and its in vivo biocompatibility in a sheep model. In vitro analysis revealed that cells preconditioned with FGF-2 and BMP-2 showed a better capacity to adhere and proliferate on the scaffold than untreated cells. BM-MSCs cultured in an osteogenic medium supplemented with FGF-2 and BMP-2 had the highest osteogenic differentiation potential, as assessed based on Alizarin Red S staining and ALP activity. qRT-PCR analysis showed increased expression of osteogenic marker genes in FGF-2- and BMP-2-treated BM-MSCs. Our pilot in vivo research showed that the implantation of an nHAP-coated PCL/HAP/ß-TCP scaffold with BM-MSCs preconditioned with FGF-2 and BMP-2 did not have an adverse effect in the sheep mandibular region and induced bone regeneration. The biocompatibility of the implanted scaffold-BM-MSC construct with sheep tissues was confirmed by the expression of early (collagen type I) and late (osteocalcin) osteogenic proteins and a lack of an elevated level of proinflammatory cytokines. These findings suggest that FGF-2 and BMP-2 enhance the osteogenic differentiation potential of MSCs grown on a scaffold, and that such a tissue engineering construct may be used to regenerate large bone defects.

Nanomedicine as an Emerging Technology to Foster Application of Essential Oils to Fight Cancer.

Natural prodrugs extracted from plants are increasingly used in many sectors, including the pharmaceutical, cosmetic, and food industries. Among these prodrugs, essential oils (EOs) are of particular importance. These biologically active volatile oily liquids are produced by medicinal and aromatic plants and characterized by a distinctive odor. EOs possess high anticancer, antibacterial, antiviral, and antioxidant potential but often are associated with low stability; high volatility; and a high risk of deterioration with exposure to heat, humidity, light, or oxygen. Furthermore, their bioavailability is limited because they are not soluble in water, and enhancements are needed to increase their potential to target specific cells or tissues, as well as for controlled release. Nanomedicine, the application of nanotechnology in medicine, may offer efficient solutions to these problems. The technology is based on creating nanostructures in which the natural prodrug is connected to or encapsulated in nanoparticles or submicron-sized capsules that ensure their solubility in water and their targeting properties, as well as controlled delivery. The potential of EOs as anticancer prodrugs is considerable but not fully exploited. This review focusses on the recent progress towards the practical application of EOs in cancer therapy based on nanotechnology applications.

Correction: Synthesis and characterizations of YZ-BDC:Eu3+,Tb3+ nanothermometers for luminescence-based temperature sensing.

[This corrects the article DOI: 10.1039/D2RA01759H.].

Synthesis and characterizations of YZ-BDC:Eu3+,Tb3+ nanothermometers for luminescence-based temperature sensing.

In the present work, nanothermometers based on amorphous zirconium metal-organic frameworks co-doped with rare-earth ions (YZ-BDC:Eu3+,Tb3+ nanothermometers) with sizes of about 10-30 nm were successfully synthesized via a microwave-assisted hydrothermal method at 120 °C for 15 min. The determined BET surfaces area, total pore volume and average pore diameter were ∼530 m2 g-1, 0.45 cm3 g-1 and 3.4 nm, respectively. Based on Fourier transform infrared spectroscopy (FTIR) and simultaneous thermal analysis (STA) results, the formation process of carboxylic acid salts and the molecular formula of the samples have been proposed. The thermometric properties of Zr-BDC:Eu3+,Tb3+ nanothermometers and their Y3+ ion co-doped counterparts (YZ-BDC:Eu3+,Tb3+) measured in the 133-573 K temperature range were compared. Moreover, the temperature-dependent CIE(x, y) chromaticity coordinates and emission color of the samples were also determined. As the temperature increased from 133 to 573 K, the emission color of Zr-BDC:Eu3+,Tb3+ nanothermometers without the presence of Y3+ ions changed from orange to red, while for YZ-BDC:Eu3+,Tb3+ nanothermometers, the emission color changed from yellow to orange, due to the strong effect of the presence of Y3+ ions on the luminescence intensity of Eu3+ and Tb3+ ions. The maximum relative sensitivity (S Rmax) in both materials was close to 0.5%/K, however, the temperature range of their occurrence was significantly shifted toward higher temperatures due to doping with Y3+ ions. The obtained results showed that doping with Y3+ ions not only enables the modulation of the useful temperature range with high relative sensitivity, but also provides improved thermal stability.

Dental Implant Healing Screws as Temporary Oral Drug Delivery Systems for Decrease of Infections in the Area of the Head and Neck.

Background: Periimplantitis is continuously one of major threats for the uneventful functioning of dental implants. Current approaches of drug delivery systems are being more commonly implemented into oral- and maxillofacial biomaterials in order to decrease the risk of implant failure due to bacterial infection. Silver nanoparticles and their compounds have been proven in eradicating oral bacteria responsible for peri-implant infections. Nevertheless, their evaluation as coating for implant abutments has not been extensively evaluated so far. This article describes a novel coating consisting of zinc oxide (ZnO) and silver (Ag) nanoparticles (NPs). This coating was used to modify healing abutments that could be used as drug delivery systems in oral implantology. Materials and Method: Nanoparticles with a ZnO + 0.1% Ag composition were produced by microwave solvothermal synthesis and then incorporated into the surface of titanium healing abutments by high-power ultrasonic deposition. Surface morphology, roughness, wettability were evaluated. Ability of biofilm formation inhibition was tested against S. mutans, S. oralis, S. aureus and E. coli. Results: ZnO+0.1%Ag NPs were sufficiently deposed on the surface of the abutments creating nanostructured coating which increased surface roughness and decreased wettability. Modified abutments significantly decreased bacterial biofilm formation. Bacteria present in SEM studies were unlikely to settle and replicate on the experimental abutments as their cells were rounded, insufficiently spread on the surface and covered with released NPs. Conclusion: Experimental nanostructured abutments were easily manufactured by high-power ultrasonic deposition and provided significant antibacterial properties. Such biomaterials could be used as temporary drug delivery abutments for prevention and treatment of intra- and extraoral peri-implant infections in the area of the head and neck.

Physicochemical Properties of Dentine Subjected to Microabrasive Blasting and Its Influence on Bonding to Self-Adhesive Prosthetic Cement in Shear Bond Strength Test: An In Vitro Study.

The aim of this in vitro study was to assess the influence of microabrasive blasting on the physicochemical properties of dentine and shear bond strength (SBS) of self-adhesive resin cement (Maxcem Elite, Kerr, Orange, CA, USA) bonded to the dentine surface. Ninety cylindrical specimens with exposed dentine of human teeth were prepared and divided into three randomized, parallel sample sets A, B, and C. Groups B and C were subjected to abrasive blasting using a micro-sandblasting device (Microetcher IIa, Danville Materials, Carlsbad, CA, USA) with two gradations of Al2O3 abrasives (Group B, abrasion with a gradation of 50 µm; group C, abrasion with a gradation of 27 µm). SEM imaging, profilometry, chemical composition analysis, contact angle measurements, surface free energy, and SBS tests were performed. The resulting data were statistically analyzed using the Statistica software (ver. 13.3, Tibco Software Inc., Palo Alto, CA, USA). Microabrasive blasting caused changes in surface topography, structural features, and the connection strength between the dentin surface and self-adhesive prosthetic cement. Air microabrasion through the multifactorial positive reorganization of the treated surface of dentine is recommended as a pretreatment method in fixed prosthodontics adhesive cementation protocols.

Nanoformulation Composed of Ellagic Acid and Functionalized Zinc Oxide Nanoparticles Inactivates DNA and RNA Viruses.

The COVID-19 pandemic has strongly impacted daily life across the globe and caused millions of infections and deaths. No drug therapy has yet been approved for the clinic. In the current study, we provide a novel nanoformulation against DNA and RNA viruses that also has a potential for implementation against COVID-19. The inorganic-organic hybrid nanoformulation is composed of zinc oxide nanoparticles (ZnO NPs) functionalized with triptycene organic molecules (TRP) via EDC/NHS coupling chemistry and impregnated with a natural agent, ellagic acid (ELG), via non-covalent interactions. The physicochemical properties of prepared materials were identified with several techniques. The hybrid nanoformulation contained 9.5 wt.% TRP and was loaded with up to 33.3 wt.% ELG. ELG alone exhibited higher cytotoxicity than both the ZnO NPs and nanoformulation against host cells. The nanoformulation efficiently inhibited viruses, compared to ZnO NPs or ELG alone. For H1N1 and HCoV-229E (RNA viruses), the nanoformulation had a therapeutic index of 77.3 and 75.7, respectively. For HSV-2 and Ad-7 (DNA viruses), the nanoformulation had a therapeutic index of 57.5 and 51.7, respectively. In addition, the nanoformulation showed direct inactivation of HCoV-229E via a virucidal mechanism. The inhibition by this mechanism was > 60%. Thus, the nanoformulation is a potentially safe and low-cost hybrid agent that can be explored as a new alternative therapeutic strategy for COVID-19.

Anti-inflammatory and antioxidant effects of nanoformulations composed of metal-organic frameworks delivering rutin and/or piperine natural agents.

Plant-derived natural medicines have been extensively studied for anti-inflammatory or antioxidant properties, but challenges to their clinical use include low bioavailability, poor solubility in water, and difficult-to-control release kinetics. Nanomedicine may offer innovative solutions that can enhance the therapeutic activity and control release kinetics of these agents, opening the way to translating them into the clinic. Two agents of particular interest are rutin (Ru), a flavonoid, and piperine (Pip), an alkaloid, which exhibit a range of pharmacological activities that include antioxidant and anti-inflammatory effects. In this work, nanoformulations were developed consisting of two metal-organic frameworks (MOFs) with surface modifications, Ti-MOF and Zr-MOF, each of them loaded with Ru and/or Pip. Both MOFs and nanoformulations were characterized and evaluated in vivo for anti-inflammatory and antioxidant effects. Loadings of ∼17 wt.% for a single pro-drug and ∼27 wt.% for dual loading were achieved. The release patterns for Ru and or Pip followed two stages: a zero-order for the first 12-hour stage, and a second stage of stable sustained release. At pH 7.4, the release patterns best fit to zero-order and Korsmeyer-Peppas kinetic models. The nanoformulations had enhanced anti-inflammatory and antioxidant effects than any of their elements singly, and those with Ru or Pip alone showed stronger effects than those with both agents. Results of assays using a paw edema model, leukocyte migration, and plasma antioxidant capacity were in agreement. Our preliminary findings indicate that nanoformulations with these agents exert better anti-inflammatory and antioxidant effects than the agents in their free form.

Drug-Releasing Antibacterial Coating Made from Nano-Hydroxyapatite Using the Sonocoating Method.

Medical implant use is associated with a risk of infection caused by bacteria on their surface. Implants with a surface that has both bone growth-promoting properties and antibacterial properties are of interest in orthopedics. In the current study, we fabricated a bioactive coating of hydroxyapatite nanoparticles on polyether ether ketone (PEEK) using the sonocoating method. The sonocoating method creates a layer by immersing the object in a suspension of nanoparticles in water and applying a high-power ultrasound. We show that the simple layer fabrication method results in a well-adhering layer with a thickness of 219 nm to 764 nm. Dropping cefuroxime sodium salt (Cef) antibiotic on the coated substrate creates a layer with a drug release effect and antibacterial activity against Staphylococcus aureus. We achieved a concentration of up to 1 mg of drug per cm2 of the coated substrate. In drug release tests, an initial burst was observed within 24 h, accompanied by a linear stable release effect. The drug-loaded implants exhibited sufficient activity against S. aureus for 24 and 168 h. Thus, the simple method we present here produces a biocompatible coating that can be soaked with antibiotics for antibacterial properties and can be used for a range of medical implants.

Enhanced Activity and Sustained Release of Protocatechuic Acid, a Natural Antibacterial Agent, from Hybrid Nanoformulations with Zinc Oxide Nanoparticles.

Hybrid nanostructures can be developed with inorganic nanoparticles (NPs) such as zinc oxide (ZnO) and natural antibacterials. ZnO NPs can also exert antibacterial effects, and we used them here to examine their dual action in combination with a natural antibacterial agent, protocatechuic acid (PCA). To produce hybrid nanoformulations, we functionalized ZnO NPs with four types of silane organic molecules and successfully linked them to PCA. Physicochemical assessment confirmed PCA content up to ~18% in hybrid nanoformulations, with a PCA entrapment efficiency of ~72%, indicating successful connection. We then investigated the in vitro release kinetics and antibacterial effects of the hybrid against Staphylococcus aureus. PCA release from hybrid nanoformulations varied with silane surface modification. Within 98 h, only 8% of the total encapsulated PCA was released, suggesting sustained long-term release. We used nanoformulation solutions collected at days 3, 5, and 7 by disc diffusion or log reduction to evaluate their antibacterial effect against S. aureus. The hybrid nanoformulation showed efficient antibacterial and bactericidal effects that also depended on the surface modification and at a lower minimum inhibition concentration compared with the separate components. A hybrid nanoformulation of the PCA prodrug and ZnO NPs offers effective sustained-release inhibition of S. aureus growth.

Delivery of Natural Agents by Means of Mesoporous Silica Nanospheres as a Promising Anticancer Strategy.

Natural prodrugs derived from different natural origins (e.g., medicinal plants, microbes, animals) have a long history in traditional medicine. They exhibit a broad range of pharmacological activities, including anticancer effects in vitro and in vivo. They have potential as safe, cost-effective treatments with few side effects, but are lacking in solubility, bioavailability, specific targeting and have short half-lives. These are barriers to clinical application. Nanomedicine has the potential to offer solutions to circumvent these limitations and allow the use of natural pro-drugs in cancer therapy. Mesoporous silica nanoparticles (MSNs) of various morphology have attracted considerable attention in the search for targeted drug delivery systems. MSNs are characterized by chemical stability, easy synthesis and functionalization, large surface area, tunable pore sizes and volumes, good biocompatibility, controlled drug release under different conditions, and high drug-loading capacity, enabling multifunctional purposes. In vivo pre-clinical evaluations, a significant majority of results indicate the safety profile of MSNs if they are synthesized in an optimized way. Here, we present an overview of synthesis methods, possible surface functionalization, cellular uptake, biodistribution, toxicity, loading strategies, delivery designs with controlled release, and cancer targeting and discuss the future of anticancer nanotechnology-based natural prodrug delivery systems.

Microstructure and Mechanical Properties of Inverse Nanocomposite Made from Polylactide and Hydroxyapatite Nanoparticles.

Polymer nanocomposites have been extensively researched for a variety of applications, including medical osteoregenerative implants. However, no satisfactory solution has yet been found for regeneration of big, and so-called critical, bone losses. The requirement is to create a resorbable material which is characterised by optimum porosity, sufficient strength, and elastic modulus matching that of the bone, thus stimulating tissue regrowth. Inverse nanocomposites, where the ceramic content is larger than the polymer content, are a recent development. Due to their high ceramic content, they may offer the required properties for bone implants, currently not met by polymer nanocomposites with a small number of nanoparticles. This paper presents inverse nanocomposites composed of bioresorbable nano crystalline hydroxyapatite (HAP NPs) and polylactide (PLLA), produced by cryomilling and a warm isostatic pressing method. The following compositions were studied: 25%, 50%, and 75% of HAP NPs by volume. The mechanical properties and structure of these composites were examined. It was discovered that 50% volume content was optimal as far as compressive strength and porosity are concerned. The inverse nanocomposite with 50% nanoceramics volume displayed a compressive strength of 99 ± 4 MPa, a contact angle of 50°, and 25% porosity, which make this material a candidate for further studies as a bioresorbable bone implant.

Preparation and Characterisation of Poly(methyl metacrylate)-Titanium Dioxide Nanocomposites for Denture Bases.

Introduction of titanium dioxide nanoparticles (TiO2 NPs) to poly(methyl methacrylate) (PMMA) aims to improve the mechanical, microbiological and tribological properties of dental prosthesis bases. The aim of the research was to assess the polymerisation time and the change in the colour of the new biomaterial. Samples with the 1 wt% and 2 wt% content of TiO2 additionally modified by ultrasounds were created. The effectiveness of ultrasounds was assessed by comparing the average size of conglomerates in a liquid acrylic resin monomer by means of a dynamic light scattering (DLS) analysis. The biomaterial structure was assessed by the energy-dispersive X-ray spectroscopy (EDS) analysis. The colour change was analysed by means of a colorimetric test and provided in the CIE (Commission internationale de l'éclairage) L*a*b* and RGB (Red Green Blue) colour palette. It was observed during the DLS test that the ultrasonic homogenisation process caused an increase in the suspension heterogeneity. The EDS analysis confirmed the presence of nanoparticles sized below 100 nm, which constitutes a ground for calling the new biomaterial a nanocomposite. The addition of TiO2 NPs as well as the ultrasounds result in the reduction of the average PMMA polymerisation time. The obtained data reveal that the addition of both 1 wt% and 2 wt% causes a considerable change in the PMMA colour: its whitening. To summarise, the reduced polymerisation time of the new biomaterial fully enables performance of standard procedures related to creation of dental prosthesis bases. Due to the considerable change in the colour, the clinical application is limited to performance of repairs or relining of the prosthesis, where the new material is located in an unaesthetic zone.

Virucidal Action Against Avian Influenza H5N1 Virus and Immunomodulatory Effects of Nanoformulations Consisting of Mesoporous Silica Nanoparticles Loaded with Natural Prodrugs.

BACKGROUND: Combating infectious diseases caused by influenza virus is a major challenge due to its resistance to available drugs and vaccines, side effects, and cost of treatment. Nanomedicines are being developed to allow targeted delivery of drugs to attack specific cells or viruses. MATERIALS AND METHODS: In this study, mesoporous silica nanoparticles (MSNs) functionalized with amino groups and loaded with natural prodrugs of shikimic acid (SH), quercetin (QR) or both were explored as a novel antiviral nanoformulations targeting the highly pathogenic avian influenza H5N1 virus. Also, the immunomodulatory effects were investigated in vitro tests and anti-inflammatory activity was determined in vivo using the acute carrageenan-induced paw edema rat model. RESULTS: Prodrugs alone or the MSNs displayed weaker antiviral effects as evidenced by virus titers and plaque formation compared to nanoformulations. The MSNs-NH2-SH and MSNs-NH2-SH-QR2 nanoformulations displayed a strong virucidal by inactivating the H5N1 virus. They induced also strong immunomodulatory effects: they inhibited cytokines (TNF-α, IL-1ß) and nitric oxide production by approximately 50% for MSNs-NH2-SH-QR2 (containing both SH and QR). Remarkable anti-inflammatory effects were observed during in vivo tests in an acute carrageenan-induced rat model. CONCLUSION: Our preliminary findings show the potential of nanotechnology for the application of natural prodrug substances to produce a novel safe, effective, and affordable antiviral drug.