Graphene oxide (GO) has recently captured tremendous attention, but only few functionalized graphene derivatives were used as fillers, and insightful studies dealing with the thermal, mechanical, and biological effects of graphene surface functionalization are currently missing in the literature. Herein, reduced graphene oxide (rGO), phosphorylated graphene oxide (PGO), and trimethylsilylated graphene oxide (SiMe3GO) were prepared by the post-modification of GO. The electrostatic interactions of these fillers with chitosan afforded colloidal solutions that provide, after water evaporation, transparent and flexible chitosan-modified graphene films. All reinforced chitosan–graphene films displayed improved mechanical, thermal, and antibacterial (S. aureus, E. coli) properties compared to native chitosan films. Hemolysis, intracellular catalase activity, and hemoglobin oxidation were also observed for these materials. This study shows that graphene functionalization provides a handle for tuning the properties of graphene-reinforced nanocomposite films and customizing their functionalities.

Controlled cellulose fragmentation and its downsizing to micro-and nanocrystals have recently captured tremendous attention to access sustainable nanomaterials. Hitherto, few functionalized cellulose derivatives have been used as fillers, and additional knowledge is needed to establish an accurate structure−performance relationship in the realm of sustainable nanocomposites. Herein, a range of phosphorylated microcellulose (MCC) and nanosized cellulose (CNC) have been prepared and used as reinforcing fillers to build transparent and flexible cellulose-filled chitosan nanostructured films. Regardless of their functionalization, all nanocellulose fillers reach good dispersion in the matrix, while those that are microcellulose aggregate slightly inside of the films. Distinctively, improved thermal stability was seen for chitosan films reinforced with cyclotriphosphazene grafted on cellulose nanocrystals (PN-CNC), where only half weight of the bioplastic was decomposed at 700 °C. Moreover, better mechanical properties were obtained using nanocellulose instead of microcellulose as fillers, with PN-CNC-filled chitosan reaching the highest value of 1.649 MPa in tensile modulus compared to 1.195 MPa for neat chitosan films. Phosphorylated cellulose fillers (P-CNC and P-MCC) also bring interesting antibacterial and intercellular catalase activities, compared to neat chitosan and unmodified cellulose-filled chitosan. In total, this study sheds light on the pivotal role of cellulose phosphorylation in improving the thermal, mechanical, and biological properties of the next generation of rationally designed bioplastics.

Pyrovalerone derivatives (α-pyrrolidinophenones) form a branch of synthetic cathinones, a second most prominent group of novel psychoactive substances. Although the toxicity of 3,4-MDPV, a progenitor of the α-pyrrolidinophenones, is well described, little is known of the potential cytotoxicity of the new members of this group entering the recreational drug market each year. The present study assesses the cytotoxicity of members of the α-pyrrolidinophenone group, i.e., α-PVP, its longer side-chain derivatives PV8 and PV9, and their 4-fluoro- and 4-methoxy-analogs, against model cell lines for the nervous system (SH-SY5Y), liver (Hep G2) and upper airway epithelium (RPMI 2650), and cardiomyocytes (H9C2(2-1)). Additionally, an impact of pyrovalerones on the fluidity of the plasma membrane, as the potential mechanism of their cytotoxicity, was examined. The longer side-chain α-pyrrolidinophenones and their fluoro- and methoxy-analogs produce more pronounced maximal cytotoxicity, with regard to mitochondrial activity and cell membrane integrity, than the five-carbon α-PVP and its substituted derivatives. The report demonstrates, for the first time, that changes of fluidity of the interior part of plasma membrane contribute to the cytotoxicity of pyrovalerone derivatives, in addition to the previously reported mechanisms. Taking into consideration our previous findings that PV8 and PV9 produce weaker psychostimulatory effects than α-PVP, the higher cytotoxicity of the new generation of pyrovalerones can pose a serious threat to abusers, as it is possible that longer-chain compounds may be taken in higher doses to obtain similar levels of stimulation.

Synthetic materials commonly used in the packaging industry generate a considerable amount of waste each year. Chitosan is a promising feedstock for the production of functional biomaterials. From a biological point of view, chitosan is very attractive for food packaging. The purposes of this study were to evaluate the antibacterial activity of a set of chitosan-metal oxide films and different chitosan-modified graphene (oxide) films against two foodborne pathogens: Campylobacter jejuni ATCC 33560 and Listeria monocytogenes 19115. Moreover, we wanted to check whether the incorporation of antimicrobial constituents such as TiO2, ZnO, Fe2O3, Ag, and graphene oxide (GO) into the polymer matrices can improve the antibacterial properties of these nanocomposite films. Finally, this research helps elucidate the interactions of these materials with eukaryotic cells. All chitosan-metal oxide films and chitosan-modified graphene (oxide) films displayed improved antibacterial (C. jejuni ATCC 33560 and L. monocytogenes 19115) properties compared to native chitosan films. The CS-ZnO films had excellent antibacterial activity towards L. monocytogenes (90% growth inhibition). Moreover, graphene-based chitosan films caused high inhibition of both tested strains. Chitosan films with graphene (GO, GOP, GOP-HMDS, rGO, GO-HMDS, rGOP), titanium dioxide (CS-TiO2 20:1a, CS-TiO2 20:1b, CS-TiO2 2:1, CS-TiO2 1:1a, CS-TiO2 1:1b) and zinc oxide (CS-ZnO 20:1a, CS-ZnO 20:1b) may be considered as a safe, non-cytotoxic packaging materials in the future.

Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to efficient and safe therapies. Advanced nanosystems and stimuli-responsive materials are available and well-studied technologies that may contribute to this effort. The present study deals with the development of functional chimeric nanocarriers composed of a phospholipid and a diblock copolymer, for the incorporation, delivery and pH-responsive release of the antiglioma agent TRAM-34 inside glioblastoma cells. Nanocarrier analysis included light scattering, protein incubation and electron microscopy, and fluorescence anisotropy and thermal analysis techniques were also applied. Biological assays were carried out in order to evaluate the nanocarrier nanotoxicity in vitro and in vivo, as well as to evaluate antiglioma activity. The nanosystems were able to successfully manifest functional properties under pH conditions, and their biocompatibility and cellular internalization were also evident. The chimeric nanoplatforms presented herein have shown promise for biomedical applications so far and should be further studied in terms of their ability to deliver TRAM-34 and other therapeutic molecules to glioblastoma cells.

Marine polysaccharides are believed to be promising wound-dressing nanomaterials because of their biocompatibility, antibacterial and hemostatic activity, and ability to easily shape into transparent films, hydrogels, and porous foams that can provide a moist micro-environment and adsorb exudates. Current efforts are firmly focused on the preparation of novel polysaccharide-derived nanomaterials functionalized with chemical objects to meet the mechanical and biological requirements of ideal wound healing systems. In this contribution, we investigated the characteristics of six different cellulose-filled chitosan transparent films as potential factors that could help to accelerate wound healing. Both microcrystalline and nano-sized cellulose, as well as native and phosphorylated cellulose, were used as fillers to simultaneously elucidate the roles of size and functionalization. The assessment of their influences on hemostatic properties indicated that the tested nanocomposites shorten clotting times by affecting both the extrinsic and intrinsic pathways of the blood coagulation system. We also showed that all biocomposites have antioxidant capacity. Moreover, the cytotoxicity and genotoxicity of the materials against two cell lines, human BJ fibroblasts and human KERTr keratinocytes, was investigated. The nature of the cellulose used as a filler was found to influence their cytotoxicity at a relatively low level. Potential mechanisms of cytotoxicity were also investigated; only one (phosphorylated microcellulose-filled chitosan films) of the compounds tested produced reactive oxygen species (ROS) to a small extent, and some films reduced the level of ROS, probably due to their antioxidant properties. The transmembrane mitochondrial potential was very slightly lowered. These biocompatible films showed no genotoxicity, and very importantly for wound healing, most of them significantly accelerated migration of both fibroblasts and keratinocytes.

Micrometer-thicker, biologically responsive nanocomposite films were prepared starting from alginate-metal alkoxide colloidal solution followed by sol-gel chemistry and solvent removal through evaporation-induced assembly. The disclosed approach is straightforward and highly versatile, allowing the entrapment and growth of a set of glassy-like metal oxide within the network of alginate and their shaping as crake-free transparent and flexible films. Immersing these films in aqueous medium triggers alginate solubilization, and affords water-soluble metal oxides wrapped in a biocompatible carbohydrate framework. Biological activity of the nano-composites films was also studied including their hemolytic activity, methemoglobin, prothrombin, and thrombine time. The effect of the films on fibroblasts and keratinocytes of human skin was also investigated with a special emphasis on the role played by the incorporated metal oxide. This comparative study sheds light on the crucial biological response of the ceramic phase embedded inside of the films, with titanium dioxide being the most promising for wound healing purposes.

Wound healing is a complex process that engages skin cells, the blood, the immune system and a number of circulating substances in the body. Infections, contamination of the wound or a vast area of damage complicate and delay the natural process of skin regeneration. The incidence of hard-to-heal wounds is an increasingly common problem, because they can significantly impair the quality of life of the patient. For this reason, it is extremely important to look for factors (drugs, dressings or other substances) that could accelerate and relieve wound healing. Among many compounds in the area of medical engineering interest, attention should be paid to natural polysaccharides, e.g. chitosan and alginate. This article is devoted to biomaterials that play an important role in the treatment of chronic wounds. These include the following: hydrogels, non-wovens, membranes and chitosan sponges as well as chitosan-alginate composites or chitosan composites combined with zinc oxide and nanosilver. The material, which has chitosan as a base, works on all stages of the healing process. Many in vitro, in vivo and clinical studies that provide the basis for using chitosan materials as a substitute for conventional bandages and dressings have been carried out. At the stage of hemostasis, it accelerates platelet aggregation and the formation of a fibrin clot. In the inflamed stage, they cause the proliferation of neutrophils and macrophages that cleanse the wound, releasing cytokines at the wound site. Studies have shown that chitosan mimics the native extracellular matrix, providing the optimal microenvironment for the wound.