Bio-Nanohybrid Gelatin/Quantum Dots for Cellular Imaging and Biosensing Applications.

The bio-nanohybrid gelatin protein/cadmium sulfide (Gel/CdS) quantum dots (QDs) have been designed via a facile one-pot strategy. The amino acids group of gelatin chelate Cd2+ and grow CdS QDs without any agglomeration. The 1H NMR spectra indicate that during the above process there are no alterations of the gelatin protein structure conformation and chemical functionalities. The prepared Gel/CdS QDs were characterized and their potential as a system for cellular imaging and the electrochemical sensor for hydrogen peroxide (H2O2) detection applications were investigated. The obtained results demonstrate that the developed Gel/CdS QDs system could offer a simple and convenient operating strategy both for the class of contrast agents for cell labeling and electrochemical sensors purposes.

Development and Characterization of Novel Films Based on Sulfonamide-Chitosan Derivatives for Potential Wound Dressing.

The objective of this study was to develop new films based on chitosan functionalized with sulfonamide drugs (sulfametoxydiazine, sulfadiazine, sulfadimetho-xine, sulfamethoxazol, sulfamerazine, sulfizoxazol) in order to enhance the biological effects of chitosan. The morphology and physical properties of functionalized chitosan films as well the antioxidant effects of sulfonamide-chitosan derivatives were investigated. The chitosan-derivative films showed a rough surface and hydrophilic properties, which are very important features for their use as a wound dressing. The film based on chitosan-sulfisoxazol (CS-S6) showed the highest swelling ratio (197%) and the highest biodegradation rate (63.04%) in comparison to chitosan film for which the swelling ratio was 190% and biodegradation rate was only 10%. Referring to the antioxidant effects the most active was chitosan-sulfamerazine (CS-S5) which was 8.3 times more active than chitosan related to DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging ability. This compound showed also a good ferric reducing power and improved total antioxidant capacity.

Experimental and in silico insights: interaction of dimethyl sulphoxide with 1-hexyl-2-methyl imidazolium bromide/1-octyl-2-methyl imidazolium bromide at different temperatures.

Ionic liquids have gained attention as 'designer solvents' since they offer a broad spectrum of properties that can be tuned by altering the constituent ions. In this work, 1-alkyl-2-methyl imidazolium-based ionic liquids with two different alkyl chains (alkyl = hexyl and octyl) have been synthesized and characterized. Since the binary mixture of ionic liquids with molecular solvents can give rise to striking physicochemical properties, the interaction of the synthesized room temperature ionic liquids, 1-hexyl-2-methyl imidazolium bromide [HMIM][Br]/1-octyl-2-methyl imidazolium bromide [OMIM][Br] with DMSO has been examined through density and specific conductance at T = (303.15, 308.15, 313.15 and 318.15) K under atmospheric pressure. The obtained molar volume and excess molar volume are fitted to the Redlich-Kister polynomial equation, and the standard deviation is noted. The positive excess molar volume at elevated temperatures indicates volume expansion due to the mutual loss of dipolar association and differences in the sizes and shapes of the constituent molecules. To have a better understanding of the reactivity and efficacy of 1-hexyl-2-methyl imidazolium bromide and 1-octyl-2-methyl imidazolium bromide with DMSO, the Becke, 3-parameter, Lee-Yang-Parr (B3LYP) correlation function of density functional theory (DFT) has been used. The ORCA Program version 4.0 calculates the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy. The effective reactivities of both the compounds that showed an energy band gap (ΔE), i.e., the difference between ELUMO and EHOMO, are 7.147 and 8.037 kcal mol-1.

Cationic polymers and their therapeutic potential.

The last decade has witnessed enormous research focused on cationic polymers. Cationic polymers are the subject of intense research as non-viral gene delivery systems, due to their flexible properties, facile synthesis, robustness and proven gene delivery efficiency. Here, we review the most recent scientific advances in cationic polymers and their derivatives not only for gene delivery purposes but also for various alternative therapeutic applications. An overview of the synthesis and preparation of cationic polymers is provided along with their inherent bioactive and intrinsic therapeutic potential. In addition, cationic polymer based biomedical materials are covered. Major progress in the fields of drug and gene delivery as well as tissue engineering applications is summarized in the present review.

Biosensing Systems Based on Graphene Oxide Fluorescence Quenching Effect.

Graphene oxide (GO) is a versatile material obtained by the strong oxidation of graphite. Among its peculiar properties, there is the outstanding ability to significantly alter the fluorescence of many common fluorophores and dyes. This property has been exploited in the design of novel switch-ON and switch-OFF fluorescence biosensing platforms for the detection of a plethora of biomolecules, especially pathological biomarkers and environmental contaminants. Currently, novel advanced strategies are being developed for therapeutic, diagnostic and theranostic approaches to widespread pathologies caused by viral or bacterial agents, as well as to cancer. This work illustrates an overview of the most recent applications of GO-based sensing systems relying on its fluorescence quenching effect.

Facile fabrication of plasmonic Ag/ZIF-8: an efficient catalyst for investigation of antibacterial, haemolytic and photocatalytic degradation of antibiotics.

Present article represents the fabrication of plasmonic Ag/ZIF-8 composite and its effect on antibacterial, haemolytic and photocatalytic degradation of antibiotics. Ag/ZIF-8 was prepared by varying molar concentrations (1 mM, 2.5 mM, and 5 mM) of AgNO3 into ZIF-8 using NaBH4 as a reducing agent by the sol-gel process. The material was then characterised using the XRD, XPS, FTIR, SEM, HRTEM, UVDRS, BET and EIS techniques. When it comes to breaking down the antibiotic CIP, the optimised Ag2.5/ZIF-8 exhibits the strongest photocatalytic capability, with a degradation efficiency of 82.3% after 90 minutes. Due to LSPR (Localised Surface Plasmon Resonance) as well as the efficient movement and separation of the interfaces of photo-generated charge carriers in Ag2.5/ZIF-8 may be the causes of this increase in photocatalytic degradation. The effect of several parameters, such as pH, a variety of catalysts, varying dose concentrations, scavenging and sustainability are being investigated. The para benzoquinone (OH˙) and citric acid (h+) the primary active species in the photocatalytic breakdown pathway, according to trapping study. Whereas, Ag5/ZIF-8 was optimised for greater antibacterial activity against S. aureus and E. coli due to the synergistic impact of Ag+ and Zn2+ in Ag5/ZIF-8 and in haemolytic experiment, all samples were discovered to be non-toxic to blood cells. Overall, the synthesised compound was discovered to be a reusable, affordable catalyst for water remediation that can also be used in biomedicine.

Additive Manufacturing of Wet-Spun Polysulfone Medical Implants.

Research on additive manufacturing (AM) of high-performance polymers provides novel materials and technologies for advanced applications in different sectors, such as aerospace and biomedical engineering. The present article is contextualized in this research trend by describing a novel AM protocol for processing a polysulfone (PSU)/N-methyl-2-pyrrolidone (NMP) solution into medical implant prototypes. In particular, an AM technique involving the patterned deposition of the PSU/NMP mixture in a coagulation bath was employed to fabricate PSU implants with different predefined shape, fiber diameter, and macropore size. Scanning electron microscopy (SEM) analysis highlighted a fiber transversal cross-section morphology characterized by a dense external skin layer and an inner macroporous/microporous structure, as a consequence of the nonsolvent-induced polymer solidification process. Physical-chemical and thermal characterization of the fabricated samples demonstrated that PSU processing did not affect its macromolecular structure and glass-transition temperature, as well as that after post-processing PSU implants did not contain residual solvent or nonsolvent. Mechanical characterization showed that the developed PSU scaffold tensile and compressive modulus could be changed by varying the macroporous architecture. In addition, PSU scaffolds supported the in vitro adhesion and proliferation of the BALB/3T3 clone A31 mouse embryo cell line. These findings encourage further research on the suitability of the developed processing method for the fabrication of customized PSU implants.

Designing of gradient scaffolds and their applications in tissue regeneration.

Gradient scaffolds are isotropic/anisotropic three-dimensional structures with gradual transitions in geometry, density, porosity, stiffness, etc., that mimic the biological extracellular matrix. The gradient structures in biological tissues play a major role in various functional and metabolic activities in the body. The designing of gradients in the scaffold can overcome the current challenges in the clinic compared to conventional scaffolds by exhibiting excellent penetration capacity for nutrients & cells, increased cellular adhesion, cell viability & differentiation, improved mechanical stability, and biocompatibility. In this review, the recent advancements in designing gradient scaffolds with desired biomimetic properties, and their implication in tissue regeneration applications have been briefly explained. Furthermore, the gradients in native tissues such as bone, cartilage, neuron, cardiovascular, skin and their specific utility in tissue regeneration have been discussed in detail. The insights from such advances using gradient-based scaffolds can widen the horizon for using gradient biomaterials in tissue regeneration applications.

Chitosan-Polyphenol Conjugates for Human Health.

Human health deteriorates due to the generation and accumulation of free radicals that induce oxidative stress, damaging proteins, lipids, and nucleic acids; this has become the leading cause of many deadly diseases such as cardiovascular, cancer, neurodegenerative, diabetes, and inflammation. Naturally occurring polyphenols have tremendous therapeutic potential, but their short biological half-life and rapid metabolism limit their use. Recent advancements in polymer science have provided numerous varieties of natural and synthetic polymers. Chitosan is widely used due to its biomimetic properties which include biodegradability, biocompatibility, inherent antimicrobial activity, and antioxidant properties. However, due to low solubility in water and the non-availability of the H-atom donor, the practical use of chitosan as an antioxidant is limited. Therefore, chitosan has been conjugated with polyphenols to overcome the limitations of both chitosan and polyphenol, along with increasing the potential synergistic effects of their combination for therapeutic applications. Though many methods have been evolved to conjugate chitosan with polyphenol through activated ester-modification, enzyme-mediated, and free radical induced are the most widely used strategies. The therapeutic efficiency of chitosan-polyphenol conjugates has been investigated for various disease treatments caused by ROS that have shown favorable outcomes and tremendous results. Hence, the present review focuses on the recent advancement of different strategies of chitosan-polyphenol conjugate formation with their advantages and limitations. Furthermore, the therapeutic applicability of the combinatorial efficiency of chitosan-based conjugates formed using Gallic Acid, Curcumin, Catechin, and Quercetin in human health has been described in detail.

Healable, Adhesive, and Conductive Nanocomposite Hydrogels with Ultrastretchability for Flexible Sensors.

In recent years, conductive hydrogels have generated tremendous attention in biomedicals and bioelectronics fields due to their excellent physiochemical properties. In this study, a physically cross-linked conducting hydrogel has been designed in combination with cellulose nanocrystalline (CNC), polyacrylic acid (PAA) chains, laurel methacrylate, and sodium dodecyl sulfate. The obtained result shows that the hydrogel prepared is ultrastretchable, mechanically robust, transparent, biocompatible, conductive, and self-healing. The mechanical property of the prepared hydrogel is optimized through variation of the CNC content. The optimal hydrogel (CNC-1/PAA) exhibits an impressive mechanics, including high stretchability (∼1800%) and compressibility, good elasticity, and fatigue resistance. Furthermore, the conductivity of the hydrogel enables tensile strain- and pressure-sensing capabilities. The CNC/PAA-based flexible sensors are successfully designed, which shows high sensitivity, fast response (290 ms), and excellent cycle stability as well as the pressure sensing capability. As a result, the designed hydrogel has the ability to sense and detect diverse human motion, including elbow/finger/wrist bending and speaking, which demonstrates that the designed self-healing conductive hydrogels have significant potential for applications in flexible electronics.

Materials and Technologies to Combat Counterfeiting of Pharmaceuticals: Current and Future Problem Tackling.

The globalization of drug trade leads to the expansion of pharmaceutical counterfeiting. The immense threat of low quality drugs to millions of patients is considered to be an under-addressed global health challenge. Analytical authentication technologies are the most effective methods to identify active pharmaceutical ingredients and impurities. However, most of these analytical testing techniques are expensive and need skilled personnel. To combat counterfeiting of drugs, the package of an increasing number of drugs is being protected through advanced package labeling technologies. Though, package labeling is only effective if the drugs are not repackaged. Therefore "in-drug labeling," instead of "drug package labeling," may become powerful tools to protect drugs. This review aims to overview how advanced micro- and nanomaterials might become interesting markers for the labeling of tablets and capsules. Clearly, how well such identifiers can be integrated into "solid drugs" without compromising drug safety and efficacy remains a challenge. Also, incorporation of tags has so far only been reported for the protection of solid drug dosage forms. No doubts that in-drug labeling technologies for "liquid drugs," like injectables which contain expensive peptides, monoclonal antibodies, vaccines, dermal fillers, could help to protect them from counterfeiting as well.

Designing of Chitosan Derivatives Nanoparticles with Antiangiogenic Effect for Cancer Therapy.

Angiogenesis is a physiological process involving the growth of new blood vessels, which provides oxygen and required nutrients for the development of various pathological conditions. In a tumor microenvironment, this process upregulates the growth and proliferation of tumor cells, thus any stage of angiogenesis can be a potential target for cancer therapies. In the present study, chitosan and his derivatives have been used to design novel polymer-based nanoparticles. The therapeutic potential of these newly designed nanoparticles has been evaluated. The antioxidant and MTT assays were performed to know the antioxidant properties and their biocompatibility. The in vivo antiangiogenic properties of the nanoparticles were evaluated by using a chick Chorioallantoic Membrane (CAM) model. The obtained results demonstrate that chitosan derivatives-based nanostructures strongly enhance the therapeutic effect compared to chitosan alone, which also correlates with antitumor activity, demonstrated by the in vitro MTT assay on human epithelial cervical Hep-2 tumor cells. This study opens up new direction for the use of the chitosan derivatives-based nanoparticles for designing of antiangiogenic nanostructured materials, for future cancer therapy.

New isoniazid derivatives with improved pharmaco-toxicological profile: Obtaining, characterization and biological evaluation.

Tuberculostatic drugs are the most common drug groups with global hepatotoxicity. Awareness of potentially severe hepatotoxic reactions is vital, as hepatic impairment can be a devastating and often fatal condition. The treatment problems that may arise, within this class of medicines, are mainly of two types: adverse reactions (collateral, toxic or hypersensitive reactions) and the initial or acquired resistance of Mycobacterium tuberculosis to one or more antituberculosis drugs. Prevention of adverse reactions, increase treatment adherence and success rates, providing better control of tuberculosis (TB). In this regard, obtaining new drugs with low toxicity and high tuberculostatic potential is essential. Thus, in this work, we have designed or synthesized new derivatives of isoniazid (INH), such as new Isonicotinoylhydrazone (INH-a, INH-b and INH-c). These derivatives demonstrated good biocompatibility, antimicrobial property similar to that of parent isoniazid and last but not least, a significantly improved Pharmacotoxicological profile compared to that of isoniazid.

Oil-in-water emulsion impregnated electrospun poly(ethylene terephthalate) fiber mat as a novel tool for optical fiber cleaning.

HYPOTHESIS: The complete removal of remaining polymer debris after stripping of optical fiber cables is essential for high precision connection between two fibers. It can be anticipated that electrospun porous membranes as cleaning wipes are able to trap and retain polymer debris within their pores. Impregnation of an oil-in-water emulsion as cleaning agent lowers the interfacial tension between debris and the optical fiber thereby enabling the straightforward removal of polymer debris from the optical fiber. EXPERIMENTS: Electrospun membranes of poly(ethylene terephthalate) (PET) and cellulose acetate (CA) were obtained with fiber diameters of 0.430 µm and 2 µm respectively. The oil-in-water emulsion was formulated with 10 wt% medium chain triglyceride (MCT) and 10 wt% Tween 80 surfactant in an aqueous phosphate buffer solution. FINDINGS: In a scoring range from 0 to 5 for which the score 0 indicated superior cleaning and the score 5 referred to the least efficient cleaning, the electrospun fiber mats (without emulsion) scored within the range of 2-4 while emulsion impregnated electrospun fiber mats revealed the best score of 0. A drastic improvement was thus clearly evident from the obtained results when the cleaning emulsion was applied. The materials developed herein thus represent a new class of soft cleaning agents for optical fibers.

Mineralization of gellan gum hydrogels with calcium and magnesium carbonates by alternate soaking in solutions of calcium/magnesium and carbonate ion solutions.

Mineralization of hydrogels is desirable prior to applications in bone regeneration. CaCO3 is a widely used bone regeneration material, and Mg, when used as a component of calcium phosphate biomaterials, has promoted bone-forming cell adhesion and proliferation and bone regeneration. In this study, gellan gum hydrogels were mineralized with carbonates containing different amounts of calcium (Ca) and magnesium (Mg) by alternate soaking in, firstly, a calcium and/or magnesium ion solution and, secondly, a carbonate ion solution. This alternate soaking cycle was repeated five times. Five different calcium and/or magnesium ion solutions, containing different molar ratios of Ca to Mg ranging from Mg free to Ca free were compared. Carbonate mineral formed in all sample groups subjected to the alternate soaking cycle. Ca : Mg elemental ratio in the mineral formed was higher than in the respective mineralizing solution. Mineral formed in the absence of Mg was predominantly CaCO3 in the form of a mixture of calcite and vaterite. Increasing the Mg content in the mineral formed led to the formation of magnesian calcite and decreased the total amount of the mineral formed and its crystallinity. Hydrogel mineralization and increasing Mg content in mineral formed did not obviously improve proliferation of MC3T3-E1 osteoblast-like cells or differentiation after 7 days.

Repeated photoporation with graphene quantum dots enables homogeneous labeling of live cells with extrinsic markers for fluorescence microscopy.

In the replacement of genetic probes, there is increasing interest in labeling living cells with high-quality extrinsic labels, which avoid over-expression artifacts and are available in a wide spectral range. This calls for a broadly applicable technology that can deliver such labels unambiguously to the cytosol of living cells. Here, we demonstrate that nanoparticle-sensitized photoporation can be used to this end as an emerging intracellular delivery technique. We replace the traditionally used gold nanoparticles with graphene nanoparticles as photothermal sensitizers to permeabilize the cell membrane upon laser irradiation. We demonstrate that the enhanced thermal stability of graphene quantum dots allows the formation of multiple vapor nanobubbles upon irradiation with short laser pulses, allowing the delivery of a variety of extrinsic cell labels efficiently and homogeneously into live cells. We demonstrate high-quality time-lapse imaging with confocal, total internal reflection fluorescence (TIRF), and Airyscan super-resolution microscopy. As the entire procedure is readily compatible with fluorescence (super resolution) microscopy, photoporation with graphene quantum dots has the potential to become the long-awaited generic platform for controlled intracellular delivery of fluorescent labels for live-cell imaging.

Enzymatic, urease-mediated mineralization of gellan gum hydrogel with calcium carbonate, magnesium-enriched calcium carbonate and magnesium carbonate for bone regeneration applications.

Mineralization of hydrogel biomaterials is considered desirable to improve their suitability as materials for bone regeneration. Calcium carbonate (CaCO3 ) has been successfully applied as a bone regeneration material, but hydrogel-CaCO3 composites have received less attention. Magnesium (Mg) has been used as a component of calcium phosphate biomaterials to stimulate bone-forming cell adhesion and proliferation and bone regeneration in vivo, but its effect as a component of carbonate-based biomaterials remains uninvestigated. In the present study, gellan gum (GG) hydrogels were mineralized enzymatically with CaCO3 , Mg-enriched CaCO3 and magnesium carbonate to generate composite biomaterials for bone regeneration. Hydrogels loaded with the enzyme urease were mineralized by incubation in mineralization media containing urea and different ratios of calcium and magnesium ions. Increasing the magnesium concentration decreased mineral crystallinity. At low magnesium concentrations calcite was formed, while at higher concentrations magnesian calcite was formed. Hydromagnesite (Mg5 (CO3 )4 (OH)2 .4H2 O) formed at high magnesium concentration in the absence of calcium. The amount of mineral formed and compressive strength decreased with increasing magnesium concentration in the mineralization medium. The calcium:magnesium elemental ratio in the mineral formed was higher than in the respective mineralization media. Mineralization of hydrogels with calcite or magnesian calcite promoted adhesion and growth of osteoblast-like cells. Hydrogels mineralized with hydromagnesite displayed higher cytotoxicity. In conclusion, enzymatic mineralization of GG hydrogels with CaCO3 in the form of calcite successfully reinforced hydrogels and promoted osteoblast-like cell adhesion and growth, but magnesium enrichment had no definitive positive effect. Copyright © 2017 John Wiley & Sons, Ltd.

Ca:Mg:Zn:CO3 and Ca:Mg:CO3-tri- and bi-elemental carbonate microparticles for novel injectable self-gelling hydrogel-microparticle composites for tissue regeneration.

Injectable composites for tissue regeneration can be developed by dispersion of inorganic microparticles and cells in a hydrogel phase. In this study, multifunctional carbonate microparticles containing different amounts of calcium, magnesium and zinc were mixed with solutions of gellan gum (GG), an anionic polysaccharide, to form injectable hydrogel-microparticle composites, containing Zn, Ca and Mg. Zn and Ca were incorporated into microparticle preparations to a greater extent than Mg. Microparticle groups were heterogeneous and contained microparticles of differing shape and elemental composition. Zn-rich microparticles were 'star shaped' and appeared to consist of small crystallites, while Zn-poor, Ca- and Mg-rich microparticles were irregular in shape and appeared to contain lager crystallites. Zn-free microparticle groups exhibited the best cytocompatibility and, unexpectedly, Zn-free composites showed the highest antibacterial activity towards methicilin-resistant Staphylococcus aureus. Composites containing Zn-free microparticles were cytocompatible and therefore appear most suitable for applications as an injectable biomaterial. This study proves the principle of creating bi- and tri-elemental microparticles to induce the gelation of GG to create injectable hydrogel-microparticle composites.

pH responsive polyurethane (core) and cellulose acetate phthalate (shell) electrospun fibers for intravaginal drug delivery.

In this study we present the use of co-axial electrospinning to produce core-shell composite micro-/nano- fibers of polyurethane (PU) and cellulose acetate phthalate (CAP). The designed fibers possess enhanced mechanical properties with a tensile strength of 13.27±2.32MPa, which is a clear improvement over the existing CAP fibers that suffer from a poor mechanical strength (0.2±0.03MPa). The CAP imparts pH responsiveness to the core-shell structure giving the fibers potential for "semen sensitive" (intravaginal) drug delivery.

New antimicrobial chitosan derivatives for wound dressing applications.

Chitosan is a non-toxic, biocompatible, biodegradable natural cationic polymer known for its low imunogenicity, antimicrobial, antioxidant effects and wound-healing activity. To improve its therapeutic potential, new chitosan-sulfonamide derivatives have been designed to develop new wound dressing biomaterials. The structural, morphological and physico-chemical properties of synthesized chitosan derivatives were analyzed by FT-IR, (1)H NMR spectroscopy, scanning electron microscopy, swelling ability and porosity. Antimicrobial, in vivo testing and biodegradation behavior have been also performed. The chitosan derivative membranes showed improved swelling and biodegradation rate, which are important characteristics required for the wound healing process. The antimicrobial assay evidenced that chitosan-based sulfadiazine, sulfadimethoxine and sulfamethoxazole derivatives were the most active. The MTT assay showed that some of chitosan derivatives are nontoxic. Furthermore, the in vivo study on burn wound model induced in Wistar rats demonstrated an improved healing effect and enhanced epithelialization of chitosan-sulfonamide derivatives compared to neat chitosan. The obtained results strongly recommend the use of some of the newly developed chitosan derivatives as antimicrobial wound dressing biomaterials.