A sustainable and self-healable silk fibroin nanocomposite with antibacterial and drug eluting properties for 3D printed wound dressings.

The development of self-healable and 3D printable hydrogels with decent biocompatibility, mechanical durability, adhesiveness to tissues, and antibacterial activity is of great importance for wound healing applications. In this study, we present a sustainable and environmentally friendly composite hydrogel consisting of silk fibroin (SF), oxidized salep (OS), and kappa carrageenan nanoparticles (NPs) for efficient wound care. The injectable nanocomposite hydrogel is highly stretchable and exhibits strong tissue adhesiveness and self-healing response through Schiff-base cross-linking between OS and SF. The tunable shear-thinning viscoelastic properties of the hydrogel facilitate 3D bioprinting with excellent shape adaptability (97.7 ± 1.1% recovery), enabling the fabrication of complex-shaped constructs. In vitro release kinetics of tetracycline (TC) encapsulated in kappa carrageenan NPs indicate a distinctive Korsmeyer-Peppas profile, including an initial burst release followed by a triphasic pattern controlled by the embedded NPs within the hydrogel matrix. The composite hydrogel shows a remarkable broad-spectrum antibacterial activity with substantial zones of inhibition against S. aureus (34.00 ± 1.00 mm) and E. coli (27.60 ± 2.08 mm) after 24 h of incubation at 37 °C. The addition of TC further enhances the zones of inhibition by approximately 45% for S. aureus and 27% for E. coli. The control group without kappa NP incorporation shows no zone of inhibition, underscoring the critical role of the nanoparticles in imparting antibacterial activity to the hydrogel. Cytocompatibility assays show the high viability of fibroblast (L929) cells (>90%) in vitro. In vivo biocompatibility studies through subcutaneous implantation also do not show malignancy, infection, abscess, necrosis, epidermal or dermal modifications, or inflammation of the wounds after 14 days post-injection. H&E staining shows that the biodegradation of the developed hydrogel facilitates the growth of non-inflammatory cells, leading to the substitution of the injected hydrogel with autologous tissue. The detailed analyses affirm that the multifunctional injectable hydrogel with self-healing and antibacterial properties has high potential for wound healing and skin tissue engineering.

Hybrid ultrasound-activated nanoparticles based on graphene quantum dots for cancer treatment.

Theranostic liposomes have recently found a broad range of applications in nanomedicine due to stability, the high solubility of biomacromolecules, bioavailability, efficacy, and low adverse effects. However, the limitations of liposomes concerning the short systemic circulation in the body, limited controllability of the release rate, and the inability of in vivo imaging remain challenging. Herein, the development of novel hybrid ultrasound-activated piezoelectric nanoparticles based on a hybrid liposome nanocarrier composed of poly(vinylidene fluoride-trifluoroethylene), graphene quantum dots (GQDs), and Silibinin (a hydrophobic drug) is presented. The hybrid nanoparticles are an acoustically sensitive drug delivery platform that releases the biomacromolecules in a specific tissue area (through surface labeling with PD-1 antibody) in a non-invasive and controlled manner. We show that the developed hybrid nanoparticles (with an average outer diameter of âˆ¼ 230 ± 20 nm) enable piezoelectric-stimulated drug delivery combined with simultaneous fluorescent imaging of cancer cells in vivo. Significant enhancement (>80 % up to 240 h) and tunable drug release from the nanocarrier through enhanced diffusion from the liposome membrane are demonstrated. Cytotoxicity assays using MCF-7, 4T1, and NIH3T3 cell lines exhibit no confrontational influence of nanoparticles on cell viability up to 125 µg/ml. The PD-1 antibody on the surface of the hybrid nanocarrier allows for selective delivery to breast cancer tumors and low biodistribution to other tissues. Our results affirm that the developed ultrasound-activated piezoelectric nanoparticles have great potential as multifunctional platforms with sustainable release profiles for the delivery of hydrophobic drugs to breast cancer, especially when the ability for adequate labeling and cell monitoring is valued.

High Yield of CO and Synchronous S Recovery from the Conversion of CO2 and H2S in Natural Gas Based on a Novel Electrochemical Reactor.

H2S and CO2 are the main impurities in raw natural gas, which needs to be purified before use. However, the comprehensive utilization of H2S and CO2 has been ignored. Herein, we proposed a fully resource-based method to convert toxic gas H2S and greenhouse gas CO2 synchronously into CO and elemental S by using a novel electrochemical reactor. The special designs include that, in the anodic chamber, H2S was oxidized rapidly to S based on the I-/I3- cyclic redox system to avoid anode passivation. On the other hand, in the cathodic chamber, CO2 was rapidly and selectively reduced to CO based on a porous carbon gas diffusion electrode (GDE) modified with polytetrafluoroethylene and cobalt phthalocyanine (CoPc). A high Faraday efficiency (>95%) toward CO was achieved due to the enhanced mass transfer of CO2 on the GDE and the presence of the selective CoPc catalyst. The maximum energy efficiency of the system was more than 72.41% with a current density of over 50 mA/cm2, which was 12.5 times higher than what was previously reported on the H2S treatment system. The yields of S and CO were 24.94 mg·cm-2·h-1 and 19.93 mL·cm-2·h-1, respectively. A model analysis determined that the operation cost of the synchronous utilization of H2S and CO2 method was slightly lower than that of the single utilization of H2S in the existing natural gas purification technology. Overall, this paper provides efficient and simultaneous conversion of H2S and CO2 into S and CO.

Extraction of Hydroxyapatite Nanostructures from Marine Wastes for the Fabrication of Biopolymer-Based Porous Scaffolds.

Three-dimensional porous nanocomposites consisting of gelatin-carboxymethylcellulose (CMC) cross-linked by carboxylic acids biopolymers and monophasic hydroxyapatite (HA) nanostructures were fabricated by lyophilization, for soft-bone-tissue engineering. The bioactive ceramic nanostructures were prepared by a novel wet-chemical and low-temperature procedure from marine wastes containing calcium carbonates. The effect of surface-active molecules, including sodium dodecyl sulfate (SDS) and hexadecyltrimethylammonium bromide (CTAB), on the morphology of HA nanostructures is shown. It is demonstrated that highly bioactive and monophasic HA nanorods with an aspect ratio > 10 can be synthesized in the presence of SDS. In vitro studies on the bioactive biopolymer composite scaffolds with varying pore sizes, from 100 to 300 µm, determine the capacity of the developed procedure to convert marine wastes to profitable composites for tissue engineering.

Curcumin loading potentiates the neuroprotective efficacy of Fe3O4 magnetic nanoparticles in cerebellum cells of schizophrenic rats.

BACKGROUND: The aim of this study was to investigate the neurotoxic effects of Fe3O4 magnetic- CurNPs on isolated schizophrenia mitochondria of rats as an in vivo model. METHODS: We designed CMN loaded superparamagnetic iron oxide nanoparticles (SPIONs) (Fe3O4 magnetic- CurNPs) to achieve an enhanced therapeutic effect. The physicochemical properties of Fe3O4 magnetic- CurNPs were characterized using X-ray diffraction (XRD), and dynamic laser light scattering (DLS) and zeta potential. Further, to prove Fe3O4 magnetic- CurNPs results in superior therapeutic effects, and also, the mitochondrial membrane potential collapse, mitochondrial complex II activity, reactive oxygen species generation, ATP level, cytochrome c release and histopathology of cerebellums were determined in brains of schizophrenic rats. RESULTS: We showed that effective treatment with CMN reduced or prevented Fe3O4 magnetic-induced oxidative stress and mitochondrial dysfunction in the rat brain probably, as well as mitochondrial complex II activity, MMP, and ATP level were remarkably reduced in the cerebellum mitochondria of treated group toward control (p < 0.05). Therewith, ROS generation, and cytochrome c release were notably (p < 0.05) increased in the cerebellum mitochondria of treated group compared with control group. CONCLUSION: Taken together, Fe3O4 magnetic- CurNPs exhibits potent antineurotoxicity activity in cerebellums of schizophrenic rats. This approach can be extended to preclinical and clinical use and may have importance in schizophernia treatment in the future. To our knowledge this is the first report that provides the Fe3O4 magnetic- CurNPs could enhance the neuroprotective effects of CMN in the Schizophrenia.

Dual-Sensitive Hydrogel Nanoparticles Based on Conjugated Thermoresponsive Copolymers and Protein Filaments for Triggerable Drug Delivery.

In this study, novel hydrogel nanoparticles with dual triggerable release properties based on fibrous structural proteins (keratin) and thermoresponsive copolymers (Pluronic) are introduced. Nanoparticles were used for curcumin delivery as effective and safe anticancer agents, the hydrophobicity of which has limited their clinical applications. A drug was loaded into hydrogel nanoparticles by a single-step nanoprecipitation method. The drug-loaded nanoparticles had an average diameter of 165 and 66 nm at 25 and 37 °C, respectively. It was shown that the drug loading efficiency could be enhanced through crosslinking of the disulfide bonds in keratin. Crosslinking provided a targeted release profile under reductive conditions using an in vivo agent, glutathione (GSH), or in the presence of trypsin. Cytocompatibility assay using HeLa and L929 fibroblast cells exhibited no adverse effect of nanoparticles on cell viability up to 1 mg/mL. Besides, the green fluorescence of curcumin confirmed the uptake of drug-loaded nanoparticles by cancer cells. The redox and temperature-sensitive nanoparticles are potentially useable for the efficient delivery of hydrophobic drugs to targeted regions having a triggerable release profile.

Biochemical mechanisms of dose-dependent cytotoxicity and ROS-mediated apoptosis induced by lead sulfide/graphene oxide quantum dots for potential bioimaging applications.

Colloidal quantum dots (CQD) have attracted considerable attention for biomedical diagnosis and imaging as well as biochemical analysis and stem cell tracking. In this study, quasi core/shell lead sulfide/reduced graphene oxide CQD with near infrared emission (1100 nm) were prepared for potential bioimaging applications. The nanocrystals had an average diameter of ~4 nm, a hydrodynamic size of ~8 nm, and a high quantum efficiency of 28%. Toxicity assay of the hybrid CQD in the cultured human mononuclear blood cells does not show cytotoxicity up to 200 µg/ml. At high concentrations, damage to mitochondrial activity and mitochondrial membrane potential (MMP) due to the formation of uncontrollable amounts of intracellular oxygen radicals (ROS) was observed. Cell membrane and Lysosome damage or a transition in mitochondrial permeability were also noticed. Understanding of cell-nanoparticle interaction at the molecular level is useful for the development of new fluorophores for biomedical imaging.

On the biological performance of graphene oxide-modified chitosan/polyvinyl pyrrolidone nanocomposite membranes: In vitro and in vivo effects of graphene oxide.

Nanofibrous structures that mimic the native extracellular matrix and promote cell adhesion have attracted considerable interest for biomedical applications. In this study, GO-modified nanofibrous biopolymers (GO) were prepared by electrospinning blended solutions of chitosan (80vol%), polyvinyl pyrrolidone (15vol%), polyethylene oxide (5vol%) containing GO nanosheets (0-2wt%). It is shown that GO nanosheets significantly change the conductivity and viscosity of highly concentrated chitosan solutions, so that ultrafine and uniform fibers with an average diameter of 60nm are spinnable. The GO-reinforced nanofibers with controlled pore structure exhibit enhanced elastic modulus and tensile strength (150-300%) with a controllable water permeability to meet the required properties of natural skins. Potential use of the GO-modified biocomposites for tissue engineering is demonstrated in mesenchymal stem cell lines extracted from rat's bone marrow. The biocompatibility assay and SEM imaging reveal that the nanofibrous structure promotes the attachment and maintained characteristic cell morphology and viability up to 72h. In-vivo evaluations in rats show that a faster and more efficient wound closure rate (about 33%) are attained for the 1.5% GO nanofibrous membrane as compared with control (sterile gauze sponges).

In-situ solvothermal processing of polycaprolactone/hydroxyapatite nanocomposites with enhanced mechanical and biological performance for bone tissue engineering.

The interest in biodegradable polymer-matrix nanocomposites with bone regeneration potential has been increasing in recent years. In the present work, a solvothermal process is introduced to prepare hydroxyapatite (HA) nanorod-reinforced polycaprolactone in-situ. A non-aqueous polymer solution containing calcium and phosphorous precursors is prepared and processed in a closed autoclave at different temperatures in the range of 60-150 °C. Hydroxyapatite nanorods with varying aspect ratios are formed depending on the processing temperature. X-ray diffraction analysis and field-emission scanning electron microscopy indicate that the HA nanorods are semi-crystalline. Energy-dispersive X-ray spectroscopy and Fourier transform infrared spectrometry determine that the ratio of calcium to phosphorous increases as the processing temperature increases. To evaluate the effect of in-situ processing on the mechanical properties of the nanocomposites, highly porous scaffolds (>90%) containing HA nanorods are prepared by employing freeze drying and salt leaching techniques. It is shown that the elastic modulus and strength of the nanocomposites prepared by the in-situ method is superior (∼15%) to those of the ex-situ samples (blended HA nanorods with the polymer solution). The enhanced bone regeneration potential of the nanocomposites is shown via an in vitro bioactivity assay in a saturated simulated body fluid. An improved cell viability and proliferation is also shown by employing (3-(4,5- dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) (MTT) assay in human osteosarcoma cell lines. The prepared scaffolds with in vitro regeneration capacity could be potentially useful for orthopaedic applications and maxillofacial surgery.

Smart Polymeric Hydrogels for Cartilage Tissue Engineering: A Review on the Chemistry and Biological Functions.

Stimuli responsive hydrogels (SRHs) are attractive bioscaffolds for tissue engineering. The structural similarity of SRHs to the extracellular matrix (ECM) of many tissues offers great advantages for a minimally invasive tissue repair. Among various potential applications of SRHs, cartilage regeneration has attracted significant attention. The repair of cartilage damage is challenging in orthopedics owing to its low repair capacity. Recent advances include development of injectable hydrogels to minimize invasive surgery with nanostructured features and rapid stimuli-responsive characteristics. Nanostructured SRHs with more structural similarity to natural ECM up-regulate cell-material interactions for faster tissue repair and more controlled stimuli-response to environmental changes. This review highlights most recent advances in the development of nanostructured or smart hydrogels for cartilage tissue engineering. Different types of stimuli-responsive hydrogels are introduced and their fabrication processes through physicochemical procedures are reported. The applications and characteristics of natural and synthetic polymers used in SRHs are also reviewed with an outline on clinical considerations and challenges.

High Antimicrobial Activity and Low Human Cell Cytotoxicity of Core-Shell Magnetic Nanoparticles Functionalized with an Antimicrobial Peptide.

Superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with antimicrobial agents are promising infection-targeted therapeutic platforms when coupled with external magnetic stimuli. These antimicrobial nanoparticles (NPs) may offer advantages in fighting intracellular pathogens as well as biomaterial-associated infections. This requires the development of NPs with high antimicrobial activity without interfering with the biology of mammalian cells. Here, we report the preparation of biocompatible antimicrobial SPION@gold core-shell NPs based on covalent immobilization of the antimicrobial peptide (AMP) cecropin melittin (CM) (the conjugate is named AMP-NP). The minimal inhibitory concentration (MIC) of the AMP-NP for Escherichia coli was 0.4 µg/mL, 10-times lower than the MIC of soluble CM. The antimicrobial activity of CM depends on the length of the spacer between the CM and the NP. AMP-NPs are taken up by endothelial (between 60 and 170 pg of NPs per cell) and macrophage (between 18 and 36 pg of NPs per cell) cells and accumulate preferentially in endolysosomes. These NPs have no significant cytotoxic and pro-inflammatory activities for concentrations up to 200 µg/mL (at least 100 times higher than the MIC of soluble CM). Our results in membrane models suggest that the selectivity of AMP-NPs for bacteria and not eukaryotic membranes is due to their membrane compositions. The AMP-NPs developed here open new opportunities for infection-site targeting.

A new approach for the in vitro identification of the cytotoxicity of superparamagnetic iron oxide nanoparticles.

Superparamagnetic iron oxide nanoparticles (SPIONs) are increasingly used in medical applications, such as targeting delivery and imaging. In the future, patients are more likely to be exposed to pharmaceutical products containing such particles. The study of toxicity of SPIONs has become of great importance in recent years, although the published data in this arena is limited. The aim of the present work is to investigate the cytotoxicity of SPIONs and the effect of the particles on the cell medium components. For this purpose, uncoated and polyvinyl alcohol (PVA) coated SPIONs with narrow size distribution were synthesized via a well-known coprecipitation method. The mouse fibroblast cell line L929 was exposed to SPIONs to probe the toxicity of magnetic nanoparticles during the bio application. Changes to the cell medium caused by SPIONs were analyzed with zeta potential measurements, ultraviolet visible spectroscopy (UV/vis) and the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay. It is observed that gas vesicles are formed in SPION-treated cells. Toxicity is conventionally explained by changes in the DMEM's pH and composition due to the tendency of SPIONs to interact with biomolecules. A new procedure is proposed to examine the in vitro toxicity of nanoparticles in a more rigorous manner, which gives an improvement in the relationship between in vivo and in vitro toxicity studies.

An in vitro study of bare and poly(ethylene glycol)-co-fumarate-coated superparamagnetic iron oxide nanoparticles: a new toxicity identification procedure.

As the use of superparamagnetic iron oxide nanoparticles (SPION) in biomedical applications increases (e.g. for targeting drug delivery and imaging), patients are likely to be exposed to products containing SPION. Despite their high biomedical importance, toxicity data for SPION are limited to date. The aim of this study is to investigate the cytotoxicity of SPION and its ability to change cell medium components. Bare and poly(ethylene glycol)-co-fumarate (PEGF)-coated SPION with narrow size distributions were synthesized. The particles were prepared by co-precipitation using ferric and ferrous salts with a molar Fe3+/Fe2+ ratio of 2. Dulbecco's modified Eagle's medium (DMEM) and primary mouse fibroblast (L929) cell lines were exposed to the SPION. Variation of cell medium components and cytotoxicity due to the interactions with nanoparticles were analyzed using ultraviolet and visible spectroscopy (UV/vis) and the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay methods, respectively. The toxicity amount has been traditionally identified by changes in pH and composition in cells and DMEM due to the tendency of SPION to adsorb proteins, vitamins, amino acids and ions. For in vitro toxicity assessments, a new surface passivation procedure is proposed which can yield more reliable quantitative results. It is shown that a more reliable way of identifying cytotoxicity for in vitro assessments is to use particles with saturated surfaces via interactions with DMEM before usage.

Optimal design and characterization of superparamagnetic iron oxide nanoparticles coated with polyvinyl alcohol for targeted delivery and imaging.

Superparamagnetic iron oxide nanoparticles (SPION) with narrow size distribution and stabilized by polyvinyl alcohol (PVA) were synthesized. The particles were prepared by a coprecipitation technique using ferric and ferrous salts with a molar Fe3+/Fe2+ ratio of 2. Using a design of experiments (DOE) approach, the effect of different synthesis parameters (stirring rate and base molarity) on the structure, morphology, saturation magnetization, purity, size, and size distribution of the synthesized magnetite nanoparticles was studied by various analysis techniques including X-ray powder diffraction (XRD), thermogravimetric analysis (TGA) with differential scanning calorimetry (DSC) measurements, vibrating-sample magnetometer (VSM), transmission electron microscopy (TEM), UV-visible, and Fourier transform infrared (FT-IR) spectrometer. PVA not only stabilized the colloid but also played a role in preventing further growth of SPION followed by the formation of large agglomerates by chemisorption on the surface of particles. A rich behavior in particle size, particle formation, and super paramagnetic properties is observed as a function of molarity and stirring conditions. The particle size and the magnetic properties as well as particle shape and aggregation (individual nanoparticles, magnetic beads, and magnetite colloidal nanocrystal clusters (CNCs) are found to be influenced by changes in the stirring rate and the base molarity. The formation of magnetic beads results in a decrease in the saturation magnetization, while CNCs lead to an increase in saturation magnetization. On the basis of the DOE methodology and the resulting 3-D response surfaces for particle size and magnetic properties, it is shown that optimum regions for stirring rate and molarity can be obtained to achieve coated SPION with desirable size, purity, magnetization, and shape.