Macroporous hydrogel scaffolds are widely used in tissue engineering to promote cell growth and proliferation. Aiming to enhance cell seeding efficiency and facilitate the osteodifferentiation of mesenchymal stem cells, this study demonstrates the fabrication of pore gradient biodegradable hydrogel scaffolds inspired by natural bone structures for bone tissue engineering applications. The scaffolds were fabricated via extrusion-based 3D printing, using sequential deposition of three customized Gelatin/Oxidized Alginate - based inks with subsequent cryogenic crosslinking for permanent structure fixation. The resulting constructs were characterized and featured a continuous gradient morphology with pore sizes ranging from 10 to 300 μm. The gradient scaffolds exhibited improved mechanical stability, with a compression resistance of 149 kPa, as opposed to the non-gradient scaffold’s 116 kPa at 70% strain, and a sustained degradation rate with only a 10% loss of its initial weight within three weeks. Gradient scaffolds demonstrated a doubling of cell seeding efficiency to 47% with dense and homogeneously distributed cellular layers, as evidenced by confocal and electron microscopy. Furthermore, the gradient scaffolds demonstrated superior osteodifferentiation, with significantly higher ALP and DMP1 production and enhanced extracellular matrix mineralization compared to gradientless macroporous scaffolds. This study provides insights into the design of macroporous scaffolds and emphasizes the advantages of pore gradient over homogeneous gradientless morphologies.
Oral adsorbents have attracted increasing attention as a potential therapeutic strategy for the removal of toxic substances from the gastrointestinal tract. This review aims to provide a comprehensive overview of the structural and mechanic properties of oral adsorbents such as activated charcoal, medical clays, zeolites, silica-based adsorbents, dietary fibers (carbohydrates alginate, chitosan, pectin, carrageenan etc.), and their physicochemical properties. The review also explores the mechanisms of action of oral adsorbents, including physical adsorption, ion exchange, and specific binding interactions. Furthermore, we provide an overview of the factors that influence the adsorption capacity and selectivity of oral adsorbents. The summary of recent advances in the usage of thiolated adsorbents is discussed, which provides valuable insights into the structural and mechanistic properties of oral adsorbents and their potential as a therapeutic option for the removal of toxic substances from the gastrointestinal tract.
Background: This review summarizes data on heterocyclic systems with thiadiazole and thiazole fragments in molecules as promising antimicrobial agents. Introduction: Thiadiazole and thiazole backbones are the most favored and well-known heterocycles, a common and essential feature of various drugs. These scaffolds occupy a central position and are the main structural components of numerous drugs with a wide spectrum of action. These include antimicrobial, antituberculous, anti-inflammatory, analgesic, antiepileptic, antiviral, and anticancer agents. Method: The research is based on bibliosemantic and analytical methods using bibliographic and abstract databases, as well as databases of chemical compounds. Result: This review reports on thiadiazole and thiazole derivatives, which have important pharmacological properties. We are reviewing the structural modifications of various thiadiazole and thiazole derivatives, more specifically, the antimicrobial activity reported over the last years, as we have taken this as our main research area. 80 compounds were illustrated, and various derivatives containing hydrazone bridged thiazole and pyrrole rings, 2-pyridine and 4-pyridine substituted thiazole derivatives, compounds containing di-, tri- and tetrathiazole moieties, spiro-substituted 4- thiazolidinone-imidazoline-pyridines were analyzed. Derivatives of 5-heteroarylidene-2,4- thiazolidinediones, fluoroquinolone-thiadiazole hybrids, and others. Conclusion: 1,3,4-thiadiazoles and thiazoles are valuable resource for researchers engaged in rational drug design and development in this area.
Using free microorganisms for industrial processes has some limitations, such as the extensive consumption of substrates for growth, significant sensitivity to the microenvironment, and the necessity of separation from the product and, therefore, the cyclic process. It is widely acknowledged that confining or immobilizing cells in a matrix or support structure enhances enzyme stability, facilitates recycling, enhances rheological resilience, lowers bioprocess costs, and serves as a fundamental prerequisite for large-scale applications. This report summarizes the various cell immobilization methods, including several synthetic (polyvinylalcohol, polyethylenimine, polyacrylates, and Eudragit) and natural (gelatin, chitosan, alginate, cellulose, agar–agar, carboxymethylcellulose, and other polysaccharides) polymeric materials in the form of thin films, hydrogels, and cryogels. Advancements in the production of well-known antibiotics like penicillin and cephalosporin by various strains were discussed. Additionally, we highlighted cutting-edge research related to strain producers of peptide-based antibiotics (polymyxin B, Subtilin, Tyrothricin, varigomycin, gramicidin S, friulimicin, and bacteriocin), glusoseamines, and polyene derivatives. Crosslinking agents, especially covalent linkers, significantly affect the activity and stability of biocatalysts (penicillin G acylase, penicillinase, deacetoxycephalosporinase, L-asparaginase, β-glucosidase, Xylanase, and urease). The molecular weight of polymers is an important parameter influencing oxygen and nutrient diffusion, the kinetics of hydrogel formation, rigidity, rheology, elastic moduli, and other mechanical properties crucial for long-term utilization. A comparison of stability and enzymatic activity between immobilized enzymes and their free native counterparts was explored. The discussion was not limited to recent advancements in the biopharmaceutical field, such as microorganism or enzyme immobilization, but also extended to methods used in sensor and biosensor applications. In this study, we present data on the advantages of cell and enzyme immobilization over microorganism (bacteria and fungi) suspension states to produce various bioproducts and metabolites—such as antibiotics, enzymes, and precursors—and determine the efficiency of immobilization processes and the optimal conditions and process parameters to maximize the yield of the target products.
The relevance of active research lies in the need to develop new technologies to improve drug delivery methods for the effective treatment of wound healing. Additionally, the potential application of organogels in other areas of biomedicine, such as creating medical patches with controlled drug delivery, indicates a wide range of possibilities for using this technology. This study focuses on developing controlled drug delivery systems using organogels as carriers for ceftriaxone and ofloxacin. By selecting optimal formulations, organogels were created to immobilize the drugs, facilitating their effective and sustained release. The swelling behavior of the hydrogels was studied, showing a swelling coefficient between 16 and 32%, indicating their ability to absorb liquid relative to their weight. Drug release studies demonstrated that ceftriaxone was released 1.8 times slower than ofloxacin, ensuring a more controlled delivery. Microbiological tests confirmed that the organogels containing ofloxacin exhibited antimicrobial activity against Escherichia coli, Bacillus subtilis, and Staphylococcus aureus. However, it was a challenge to estimate activity for the model antibiotic ceftriaxone due to bacterial resistance to it. Organogel poly(vinyl alcohol) (PVA)-DMSO–alginate modifications with surfactant cetylpyridinium bromide led to the formation of a polyelectrolyte complex on the interphase, allowing further enhanced the prolonged release of the drugs. The research identified that the optimal compositions for sustained drug release were organogels with compositions PVA (10%)-PVP (1%) DMSO (50%) and PVA (10%)-DMSO (50%) formulations, illustrating the transparent nature of these organogels making them suitable for ophthalmological application. Various organogels compositions (PVA-DMSO, PVA-poly(vinylpyrrolidone)-DMSO, PVA-DMSO–alginate, PVA-DMSO-PLGA, PVA-DMSO–drug–surfactant) loaded with ceftriaxone, ofloxacin, and surfactant were prepared and characterized, highlighting their potential use in antibiotic patches for wound healing. These organogels illustrate promising results for localized treatment of infections in wounds, cuts, burns, and other skin lesions.
Background: Equine milk, including its whey proteins, is a source of nutrients and functional components in the human diet, and is especially beneficial for people with weakened immune systems, newborns, and athletes. Objectives Whey proteins in equine milk constitute approximately 20% of the total protein content and include various fractions such as albumin, globulin, and lactoferrin. Lactoferrin is one of the most extensively studied whey proteins in equine milk. Methods: HPLC-Mass analysis, enzymatic hydrolysis, modeling of 3D structure and biological activity in silico. Results: It has antioxidant, anti-inflammatory, and immunomodulatory properties, making it a promising candidate for influencing the various aspects of cardiovascular disease pathogenesis. The products of Lactoferrin hydrolysis by trypsin were confirmed using HPLC. The half-lives of the hydrolysate in the bloodstream and in an intestine-like environment were predicted in silico. Various biological activities (antihypertensive, anti-inflammatory, and antiangiogenic) were also estimated in silico and compared with the corresponding activities of lactoferrin hydrolysate amino acid sequences from camel and dromedary milk. Conclusions: The three-dimensional modeling of lactoferrin hydrolysate peptides was performed to support the development of computational models or simulations, as well as to investigate their potential antimicrobial, anti-inflammatory, or immune-modulating functions in clinical or nutritional applications.
Fabrication of scaffolds via 3D printing is a promising approach for tissue engineering. In this study, we combined 3D printing with cryogenic crosslinking to create biocompatible gelatin/oxidized alginate (Gel/OxAlg) scaffolds with large pore sizes, beneficial for bone tissue regeneration. To enhance the osteogenic effects and mechanical properties of these scaffolds, we evaluated the impact of hydroxyapatite (HAp) on the rheological characteristics of the 2.86% (1:1) Gel/OxAlg ink. We investigated the morphological and mechanical properties of scaffolds with low, 5%, and high 10% HAp content, as well as the resulting bio- and osteogenic effects. Scanning electron microscopy revealed a reduction in pore sizes from 160 to 180 µm (HAp-free) and from 120 to 140 µm for both HAp-containing scaffolds. Increased stability and higher Young’s moduli were measured for 5% and 10% HAp (18 and 21 kPa, respectively) compared to 11 kPa for HAp-free constructs. Biological assessments with mesenchymal stem cells indicated excellent cytocompatibility and osteogenic differentiation in all scaffolds, with high degree of mineralization in HAp-containing constructs. Scaffolds with 5% HAp exhibited improved mechanical characteristics and shape fidelity, demonstrated positive osteogenic impact, and enhanced bone tissue formation. Increasing the HAp content to 10% did not show any advantages in osteogenesis, offering a minor increase in mechanical strength at the cost of significantly compromised shape fidelity.
Pollution of the aquatic environment by halogen derivatives widely used as antiseptic compounds, as well as chemicals for various industrial purposes, is significant. Existing systems of bioremediation poorly solve the problem of eliminating pollution. This paper discusses the preparation of novel macroporous chitosan-based cryogels with in situ-immobilized Pd or Pt nanoparticles as a catalyst for dichlorination reactions. The formation mechanism of metal coordinated chitosan gels using Medusa software modelling and rheology (G’ and G’’) is discussed. Metal coordinated chitosan gels were subsequently converted into covalently cross-linked macroporous cryogels with in situ-immobilized Pd or Pt nanoparticles using the redox potentials difference of the reaction mixture. Noble metal nanoparticles of average size, 2.4 nm, were evenly distributed in the cryogel structure. The effectiveness of these gels as a catalyst for the decomposition of chloro-compounds o-chlorophenol, p-chlorophenol and 2,4-dichlorophenol was tested. The catalytic hydrogenation reaction was carried out using the “green reducing agent” formic acid. Increasing the excess of formic acid with heating increases the degree of conversion up to 80–90%. The CHI-GA-PdNPs cryogel at pH 6 showed better efficiency in the hydrogenation process compared to the CHI-GA-PtNPs cryogel; however, no significant difference in the degree of conversion at pH 3 was observed. The termination of a catalytic reaction in a batch mode have been studied. Several control tests were carried out to elucidate the mechanism of catalyst poisoning. The presented catalytic system may be of interest for studying reactions in a flow through mode, including the reactions for obtaining valuable chemicals.
The aim of this study was to develop and test a non-diffusion limited, high cell density bioreactor for biodegradation of various phenol derivatives. The bioreactor was obtained using a straightforward one-step preparation method using cryostructuration and direct cross-linking of bacteria into a 3D structured (sponge-like) macroporous cryogel composite material consisting of 11.6% (by mass) cells and 1.2-1.7% polymer, with approximately 87% water (in the material pores). The macroporous cryogel composite material, composed of live bacteria, has pore sizes in the range of 20-150 mu m (confirmed by SEM and Laser Scanning Confocal Microscopy). The enzymatic activity of bacteria within the cryogel structure and the effect of freezing on the viability of the cross-linked cells was estimated by MIT assay. Cryogels based on Pseudomonas mendocina, Rhodococcus koreensis and Acinetobacter radioresistens were exploited for the effective bioremediation of phenol and m-cresol, and to a lesser extent 2-chlorophenol and 4-chlorophenol, utilising these phenolic contaminants in water as their only source of carbon. For evaluation of treatment scalability the bioreactors were prepared in plastic "Kaldnes" carriers to improve their mechanical properties and allow application in batch or fluidised bed water treatment modes. (C) 2019 The Author(s). Published by Elsevier Ltd.
The last two decades revealed tremendous interest in nanoparticles synthesized via green synthesis and its wide spectra application first of all as effective antimicrobial agents. This research aims to conduct a green synthesis of silver nanoparticles (AgNPs) stabilized by amino acids and oligoproteins. Various conditions (conventional heat treatment, microwave irradiation, and UV-light irradiation pH and concentration of reagents) on yield and size of AgNPs during the synthesis were tested. Alkaline hydrolysate of paper wasp‘s nest was characterized using amino acid analysis, zeta potential, and SDS gel electrophoresis. The protein hydrolysate molecular weight distribution for AgNPs synthesis was predominantly in the range of 0.5 to 10 kDa. The kinetics of the particle synthesis was monitored via intensity change of the AgNPs’ Surface Plasmon resonance UV–V is spectroscopy. The increase of the ionic strength of the AgNP suspension by the addition of salts NaCl and KBr led to aggregation of AgNPs. Zeta potential and hydrodynamic particle size distribution of AgNPs were −46 ± 25 mV and 137 ± 73 nm, respectively. Surface Plasmon resonance peak indicates the dominance of particle size in the range 50–70 nm due to the pH, which influenced on antimicrobial activity. MIC of 7.5 μM AgNPs in combination with 50 μM of benzalkonium chloride against the E. coli strain was (6.9xE8 particles/L) and 25 μM of benzalkonium chloride, while MIC of 73 μM of AgNPs (3.45xE8 particles/L) against Staphylococcus aureus was detected. The antimicrobial effect of the AgNPs suspension irradiated by light spectra at 425 and 630 nm were studied. AgNPs obtained using microwave radiation at a neutral medium were stable for at least 3 months at 4 °C.
The present research is devoted to optimizing the green synthesis technology of silver nanoparticles (AgNP) with antibacterial properties for further external use. Standardized marigold flowers extract was utilized as reducing and stabilizing agent, which has significantly richer composition of phytochemical groups compared to its aqueous extracts. A comparative analysis of the physicochemical properties and sedimentation stability of AgNPs obtained by exposure of the reaction mixture to: UV radiation, microwave radiation and high temperature using UV–Vis spectrophotometry and Zeta potential analysis were carried out. pH effect of the reaction mixture on size distribution of AgNPs was evaluated. A good stability of AgNPs to aggregation was observed for samples generated under ultraviolet irradiation with continuous stirring. The particle size distribution obtained by UV irradiation with an average size of 80 nm and PDI 0.26. The storage of AgNPs at 4 °C resulted in some aggregation of small size AgNPs that led to the increase the absorbance at 430 nm. Thus, after one month of storage there was no following increase of the absorbance and there was non-significant aggregation over 3 months’ study. Antibacterial activity of AgNPs against S. aureus and E. coli was estimated with and without light irradiation (445 and 635 nm, 14 W). Additionally, the antioxidant activity of the plant extract and the AgNPs stabilized by the extract was estimated.
Eye drops represent the traditional form of medication delivery for the eyes, constituting approximately 90
Macroporous scaffolds have been widely used in tissue engineering to promote cell growth and proliferation. However, they often present challenges such as insufficient surface area for cell attachment, low seeding efficiency, and poor mechanical stability. This study demonstrates the fabrication of gradient hydrogel scaffolds, inspired by the structure of natural bone tissue, aimed at enhancing cell seeding efficiency and promoting the osteodifferentiation of mesenchymal stem cells. The scaffolds were fabricated via 3D printing, followed by the sequential deposition of precursor inks of variable compositions and cryogenic crosslinking for permanent structure fixation. The resulting constructs featured a continuous gradient morphology with pore sizes ranging from 40 µm to 300 µm. The gradient scaffolds exhibited improved mechanical stability, sustained degradation rates, and enhanced cell-seeding efficiency compared to conventional uniform macroporous scaffolds with an average pore diameter of 160–200 µm. Moreover, gradient scaffolds facilitate an increased cell proliferation, superior osteodifferentiation, and extracellular matrix mineralization. Our findings highlight the potential of gradient scaffolds in overcoming the inherent limitations of macroporous scaffolds, particularly for bone tissue regeneration. This study provides insights into scaffold design for bone tissue engineering, emphasizing the advantages of a gradient pore morphology in promoting cell growth, proliferation, and osteodifferentiation.
The global spread of multi-resistant pathogenic microorganisms has significantly complicated the treatment of chronic wounds. The development of novel drugs requires a substantial time investment. Hybrid materials such as nanoparticles stabilized by plant extracts are considered the best for creating efficient antiseptic substances. This paper is the first to discuss quantitative and qualitative analyses of the phytochemical constituents of the medicinal plant Artemisia terrae-albae, collected in Kazakhstan. The antimicrobial activity of the extracts, as well as of silver nanoparticles (AgNPs) stabilized by Artemisia terrae-albae extract, were evaluated. AgNPs were characterized by an average size of 82 nm or larger with a negative surface charge. TEM analysis of the obtained suspension showed a nonuniform structure of particles synthesized at a low concentration of ethyl acetate solvent in water. The SPR peak of AgNPs@Art aq. extract was detected at 420 nm, while any clear SPR peak was observed for AgNPs@Art ethylacetate extract. Diluted Artemisia terrae-albae extracts did not exhibit pronounced antimicrobial activity due to the poor solubility of compounds in water. Nevertheless, the AgNPs@Art aq. and AgNPs@Art EtAc. extracts possessed antimicrobial activity against the Pseudomonas aeruginosa ATCC 9027, Staphylococcus aureus ATCC 6538, Escherichia coli (ATCC 8739), and Candida albicans ATCC 10231 strains.
The present study deals with the synthesis and characterization of a polymer composite based on an unsaturated ester loaded with 5 wt.% triclosan, produced by co-mixing on an automated hardware system. The polymer composite's non-porous structure and chemical composition make it an ideal material for surface disinfection and antimicrobial protection. According to the findings, the polymer composite effectively inhibited (100%) the growth of Staphylococcus aureus 6538-P under exposure to physicochemical factors, including pH, UV, and sunlight, over a 2-month period. In addition, the polymer composite demonstrated potent antiviral activity against human influenza virus strain A and the avian coronavirus infectious bronchitis virus (IBV), with infectious activities of 99.99% and 90%, respectively. Thus, the resulting triclosan-loaded polymer composite is revealed to have a high potential as a surface-coating non-porous material with antimicrobial properties.
The discharge of nanoparticles into the environment, such as through industrial plants and municipal wastewater treatment plants, can pose a hazard to aquatic life. This study demonstrates the effective removal of silver nanoparticles (AgNPs) using a chitosan-based cryogel, which has potential applications in agriculture, as well as in water treatment or in industrial plants that discharge into environmentally sensitive water bodies. The adsorbent is economically viable, has high affinity toward metal nanoparticles, is biodegradable and biocompatible, and displays a good removal of nanoparticles. AgNP adsorption was monitored using UV/Vis spectroscopy and TEM analysis. SEM, nitrogen adsorption, TGA, and FTIR analysis were used for cryogel characterization. The BET model of nitrogen adsorption revealed a specific surface area of 7.7 m2/g for chitosan–glutaraldehyde (CHI–GA) cryogels. The elasticity modulus of the CHI–GA cryogel was estimated as 543 ± 54 kPa. The AgNPs were characterized by a negative charge (−38 ± 17 mV) and an average diameter of 64 nm with a polydispersity index of 0.16. The mechanism of AgNP adsorption involved electrostatic interactions between the oppositely charged surfaces of the cryogel and particles. The temperature of the cryogel preparation affected the water permeability and adsorption efficiency. CHI–GA illustrated a capacity of 63 mg/g at a flow rate of 0.8 mL/min under a solution pressure of 500–970 Pa. The increase in pressure of the model plant extract-stabilized AgNP suspension (14 mg/L AgNPs) to 3.42–3.9 kPa led to an increase in the water permeability rate to 10 mL/min and a significant decrease in the efficiency of particle removal. The CHI–GA adsorbent demonstrated up to 96.5% AgNP removal until the breakthrough point due to adsorbent saturation. The CHI–GA cryogel adsorbent (1 g) can be used for efficient filtering of about 4.5 L of contaminated water.
Species of the genus Artemisia are well known for their use as ingredients in ancient medicine. The advantage of using plant extracts compared to individual pharmaceutical ingredients is the rate of adaptation of the pathogenic microorganisms to the drug. Due to the rapid development of multidrug-resistance in microorganisms in the field, it is essential to search for novel, effective drugs with low toxicity. Therefore, the purpose of this study was to isolate and study the biologically active substances obtained from various substances in the raw materials of Artemisia cina Berg. The identification of the main biologically active components was performed using the method of chromato-mass spectrometry. Moreover, the antiviral activity of several extracts was studied using the method of measuring limiting dilutions (the Reed-Mench method), with some modifications. For the first time, the biological activity of extracts from the raw material of Artemisia cina Berg. upon the SARS-CoV-2 virus was confirmed. All the obtained extracts exhibited nontoxic effects in animals, with an LD50 greater than 2 g/kg. Comprehensive toxicological analyses are also presented in the study, such as those of the biochemical parameters of urine after one day and one week of the extracts' administration in mice at a dose of 2 g/kg body weight. In all groups of animals that received extracts of Artemisia cina Berg., a slight increase in the presence of red blood cells in their urine was observed one day following the administration of the extracts. This increase decreased somewhat after a week; however, it remained higher than the levels observed in the control animals. In the three groups, there was also a slight increase in the amount of ketones in the urine. Two weeks following the administration of the extracts to these groups, the internal organs of the animals were examined. The examination showed that the internal organs of the animals that received the extracts were not visibly different from those of the control animals in terms of their size or appearance. The weight of the internal organs of the animals that received the extracts was also similar to the weight of the internal organs of the control animals, illustrating the absence of toxicity.