Biomaterials Based on Chitosan and Its Derivatives and Their Potential in Tissue Engineering and Other Biomedical Applications—A Review

In the times of dynamically developing regenerative medicine, more and more attention is focused on the use of natural polymers. This is due to their high biocompatibility and biodegradability without the production of toxic compounds, which means that they do not hurt humans and the natural environment. Chitosan and its derivatives are polymers made most often from the shells of crustaceans and are biodegradable and biocompatible. Some of them have antibacterial or metal-chelating properties. This review article presents the development of biomaterials based on chitosan and its derivatives used in regenerative medicine, such as a dressing or graft of soft tissues or bones. Various examples of preparations based on chitosan and its derivatives in the form of gels, films, and 3D structures and crosslinking products with another polymer are discussed herein. This article summarizes the latest advances in medicine with the use of biomaterials based on chitosan and its derivatives and provides perspectives on future research activities.     

Extracts from European Propolises as Potent Tyrosinase Inhibitors

Tyrosinase is a key enzyme in the melanogenesis pathway. Melanin, the product of this process, is the main pigment of the human skin and a major protection factor against harmful ultraviolet radiation (UVR). Increased melanin synthesis due to tyrosinase hyperactivity can cause hyperpigmentation disorders, which in consequence causes freckles, age spots, melasma, or postinflammatory hyperpigmentation. Tyrosinase overproduction and hyperactivity are triggered by the ageing processes and skin inflammation as a result of oxidative stress. Therefore, the control of tyrosinase activity is the main goal of the prevention and treatment of pigmentation disorders. Natural products, especially propolis, according to their phytochemical profile abundant in polyphenols, is a very rich resource of new potential tyrosinase inhibitors. Therefore, this study focused on the assessment of the tyrosinase inhibitory potential of six extracts obtained from the European propolis samples of various origins. The results showed the potent inhibitory activity of all tested propolis extracts towards commercially available mushroom tyrosinase. The four most active propolis extracts showed inhibitory activity in the range of 86.66–93.25%. Apart from the evaluation of the tyrosinase inhibition, the performed research included UHPLC–DAD–MS/MS (ultra high performance liquid chromatography coupled with diode array detection and tandem mass spectrometry) phytochemical profiling as well as antioxidant activity assessment using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the 2,2”-azino-bis(3-ethylbenzothiazoline-6-sulfuric acid (ABTS) radical scavenging tests. Moreover, statistical analysis was used to correlate the tyrosinase inhibitory and antioxidant activities of propolis extracts with their phytochemical composition. To summarise, the results of our research showed that tested propolis extracts could be used for skin cosmeceutical and medical applications.     

Antioxidant Properties and Proximate Composition of Different Tissues of European Beaver

The chemical composition, content of cholesterol, retinol and α-tocopherol, and the total antioxidant capacity of different tissues from wild beavers were investigated. The total phenolic contents and free radical scavenging activity (DPPH and ABTS assays) were analysed spectrophotometrically, and fat-soluble vitamins were quantified using high-performance liquid chromatography. The type of tissue (skeletal muscle from loin and hind leg vs. adipose tissue from subcutaneous fat and tail) significantly affected content of all chemical components. The concentration of cholesterol was not related to total fat content. The retinol and α-tocopherol contents (µg/100 g) were significantly higher in the tail (13.0 and 391.2) and subcutaneous fat (12.2 and 371.3) compared to skeletal muscles (as an average 9.1 and 361.4). Among all tissues the tail showed significantly the highest values of DPPH (3.07 mM TE/100 g), ABTS (3.33 mM TE/100 g), and total phenolics (TPC, 543.7 mg GAE/100 g). The concentration of retinol was positively correlated with α-tocopherol (0.748, p < 0.001), and both vitamins were very strongly correlated with DPPH (0.858 and 0.886, p < 0.001), ABTS (0.894 and 0.851, p < 0.001), and TPC (0.666 and 0.913, p < 0.001). The principal component analysis proved that moisture, ash, and protein contents were representative for skeletal muscles, whereas, retinol, α-tocopherol, ABTS and DPPH accurately described the antioxidant capacity of tissue from the tail.     

Hypsizygus marmoreus as a Source of Indole Compounds and Other Bioactive Substances with Health-Promoting Activities

Hypsizygus marmoreus is an edible medicinal mushroom species with a high dietary value. In this study, the fruiting bodies of commercial and self-cultivated crops and mycelium from in vitro H. marmoreus cultures (both white and brown varieties) were evaluated. This study aimed to analyze the presence of indole compounds and other biologically active substances and determine the effect that the addition of zinc and magnesium ions to the culture medium has on the content of the tested compounds in mycelial cultures. The content of indole compounds and other organic compounds was determined using high-performance liquid chromatography, the content of bioelements was determined using flame atomic absorption spectrometry, the glucan content was determined spectrophotometrically, and the antioxidant activity of extracts was estimated using DPPH, FRAP, and ABTS methods. The results showed that H. marmoreus mycelium from in vitro cultures is a good source of indole compounds, bioelements, glucans, and lovastatin. Mycelia from in vitro cultures showed the most diverse composition of indole compounds (L-tryptophan, 5-hydroxy-L-tryptophan, tryptamine, 5-methyltryptamine, and melatonin). Additionally, in vitro cultures of H. marmoreus enriched with Zn and Mg salts increased the contents of Na, Ca, Zn, 5-methyltryptamine, melatonin, protocatechuic acid, sterols, and total glucans. Only in the case of the white variety of mycelial enriched cultures, ergothioneine and Mg levels also increased. To summarize, the content of the active compounds differed depending on the H. marmoreus variety and the tested material.     

Buckwheat Hull-Enriched Pasta: Physicochemical and Sensory Properties

This work aimed to evaluate the effect of partial replacement of semolina with 0, 1, 5, 10, 15, and 20% of ground buckwheat hull (BH) on the chemical composition, antioxidant properties, color, cooking characteristics, and sensory properties of wheat pasta. Pasta samples were prepared by dough lamination (tagliatelle shape) and dried at 55 °C until the moisture content was 11–12% (wet basis). Analyses of samples showed that the addition of BH caused an increase in fiber content in pasta from 4.31% (control pasta) to 14.15% (pasta with 20% of BH). Moreover, the brightness and yellowness of BH-enriched products were significantly decreased compared to the control sample, and the total color difference ranged from 23.84 (pasta with 1% of BH) to 32.56 (pasta with 15% BH). In addition, a decrease in optimal cooking time, as well as an increased weight index and cooking loss, was observed in BH-enriched pasta samples. Furthermore, BH-enriched cooked pasta had significantly higher total phenolic content and antioxidant activity but an unpleasant smell and taste, especially if the level of BH was higher than 10%.     

Acid–Base Equilibrium and Self-Association in Relation to High Antitumor Activity of Selected Unsymmetrical Bisacridines Established by Extensive Chemometric Analysis

Unsymmetrical bisacridines (UAs) represent a novel class of anticancer agents previously synthesized by our group. Our recent studies have demonstrated their high antitumor potential against multiple cancer cell lines and human tumor xenografts in nude mice. At the cellular level, these compounds affected 3D cancer spheroid growth and their cellular uptake was selectively modulated by quantum dots. UAs were shown to undergo metabolic transformations in vitro and in tumor cells. However, the physicochemical properties of UAs, which could possibly affect their interactions with molecular targets, remain unknown. Therefore, we selected four highly active UAs for the assessment of physicochemical parameters under various pH conditions. We determined the compounds’ pK_a dissociation constants as well as their potential to self-associate. Both parameters were determined by detailed and complex chemometric analysis of UV-Vis spectra supported by nuclear magnetic resonance (NMR) spectroscopy. The obtained results indicate that general molecular properties of UAs in aqueous media, including their protonation state, self-association ratio, and solubility, are strongly pH-dependent, particularly in the physiological pH range of 6 to 8. In conclusion, we describe the detailed physicochemical characteristics of UAs, which might contribute to their selectivity towards tumour cells as opposed to their effect on normal cells.     

Comparison of Physical Adsorption and Covalent Coupling Methods for Surface Density-Dependent Orientation of Antibody on Silicon

The orientation of antibodies, employed as capture molecules on biosensors, determines biorecognition efficiency and bioassay performance. In a previous publication we demonstrated for antibodies attached covalently to silicon that an increase in their surface amount Γ, evaluated with ellipsometry, induces changes in their orientation, which is traced directly using Time-of-Flight Secondary Ion Mass Spectroscopy combined with Principal Component Analysis. Here, we extend the above studies to antibodies adsorbed physically on a 3-aminopropyltriethoxysilane (APTES) monolayer. Antibodies physisorbed on APTES (0 ≤ Γ ≤ 3.5 mg/m²) reveal the Γ ranges for flat-on, side-on, and vertical orientation consistent with random molecular packing. The relation between orientation and Γ is juxtaposed for silicon functionalized with APTES, APTES modified with glutaraldehyde (APTES/GA) and N-hydroxysuccinimide-silane (NHS-silane). Antibody reorientation occurs at lower Γ values when physisorption (APTES) is involved rather than chemisorption (APTES/GA, NHS-silane). At high Γ values, comparable proportions of molecules adapting head-on and tail-on vertical alignment are concluded for APTES and the NHS-silane monolayer, and they are related to intermolecular dipole–dipole interactions. Intermolecular forces seem to be less decisive than covalent binding for antibodies on the APTES/GA surface, with dominant head-on orientation. Independently, the impact of glutaraldehyde activation of APTES on vertical orientation is confirmed by separate TOF-SIMS measurements.     

Effect of Polythiophene Content on Thermomechanical Properties of Electroconductive Composites

The thermal, mechanical and electrical properties of polymeric composites combined using polythiophene (PT) dopped by FeCl₃ and polyamide 6 (PA), in the aspect of conductive constructive elements for organic solar cells, depend on the molecular structure and morphology of materials as well as the method of preparing the species. This study was focused on disclosing the impact of the polythiophene content on properties of electrospun fibers. The elements for investigation were prepared using electrospinning applying two substrates. The study revealed the impact of the substrate on the conductive properties of composites. In this study composites exhibited good thermal stability, with T₅ values in the range of 230–268 °C that increased with increasing PT content. The prepared composites exhibited comparable PA T_g values, which indicates their suitability for processing. Instrumental analysis of polymers and composites was carried out using Fourier Transform Infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA) and scanning electron microscopy (SEM).     

Discovery of Potential,Dual-Active Histamine H3 Receptor Ligands with Combined Antioxidant Properties

In an attempt to find new dual acting histamine H₃ receptor (H₃R) ligands, we designed a series of compounds, structurally based on previously described in our group, a highly active and selective human histamine H₃ receptor (hH₃R) ligand KSK63. As a result, 15 obtained compounds show moderate hH₃R affinity, the best being the compound 17 (hH₃R K_i = 518 nM). Docking to the histamine H₃R homology model revealed two possible binding modes, with key interactions retained in both cases. In an attempt to find possible dual acting ligands, selected compounds were tested for antioxidant properties. Compound 16 (hH₃R K_i = 592 nM) showed the strongest antioxidant properties at the concentration of 10⁻⁴ mol/L. It significantly reduced the amount of free radicals presenting 50–60% of ascorbic acid activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, as well as showed antioxidative properties in the ferric reducing antioxidant power (FRAP) assay. Despite the yet unknown antioxidation mechanism and moderate hH₃R affinity, 16 (QD13) constitutes a starting point for the search of potential dual acting H₃R ligands-promising tools for the treatment of neurological disorders associated with increased neuronal oxidative stress.     

Impact of the Type of Crosslinking Agents on the Properties of Modified Sodium Alginate/Poly(vinyl Alcohol) Hydrogels

Here, we report on studies on the influence of different crosslinking methods (ionic and chemical) on the physicochemical (swelling ability and degradation in simulated body fluids), structural (FT-IR spectra analysis) and morphological (SEM analysis) properties of SA/PVA hydrogels containing active substances of natural origin. First, an aqueous extract of Echinacea purpurea was prepared using a Soxhlet apparatus. Next, a series of modified SA/PVA-based hydrogels were obtained through the chemical crosslinking method using poly(ethylene glycol) diacrylate (PEGDA, M_n = 700 g/mol) as a crosslinking agent and, additionally, the ionic reaction in the presence of a 5% w/v calcium chloride solution. The compositions of SA/PVA/E. purpurea-based hydrogels contained a polymer of natural origin—sodium alginate (SA, 1.5% solution)—and a synthetic polymer—poly(vinyl alcohol) (PVA, M_n = 72,000 g/mol, 10% solution)—in the ratio 2:1, and different amounts of the aqueous extract of E. purpurea—5, 10, 15 or 20% (v/v). Additionally, the release behavior of echinacoside from the polymeric matrix was evaluated in phosphate-buffered saline (PBS) at 37 °C. The results indicate that the type of the crosslinking method has a direct impact on the release profile. Consequently, it is possible to design a system that delivers an active substance in a way that depends on the application.