Ekaterina Igorevna Shishatskaya

• Prof. MD.
• Head of Biomedical Division at Siberian Federal University

In this work, spray-dried poly(3-hydroxybutyrate-co-3-hydroxyvalerate) microparticles (P(3HB-co-3HV) MPs) containing conventional antibacterial drug rifampicin (RIF), as well as novel cytostatic ozonide (OZ) were obtained and characterized. The effect of drug chemical structure on its encapsulation and release profile, as well as MPs characteristic...

In the field of tissue engineering, the architecture of a scaffold plays a critical role in determining how cells behave and how new tissue structures are formed. In this study, we have for the first time developed and compared four different types of 3D printed scaffolds made from biodegradable polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate)....

Background and purpose The use of drug delivery systems to enhance the efficacy of existing antimicrobial drugs is one of the promising approaches to combat bacterial resistance. The simultaneous presence of a polycationic biopolymer (chitosan) and an antibacterial drug (ceftazidime) in polyhydroxyalkanoates microparticles is more effective since i...

The control of the surface topography of biomaterials is a key factor for the management of post-implantation recovery processes. The study of the influence of the nanorelief of polyhydroxyalkanoate (PHA) films on the functional state of cells involved in tissue healing process is important for the development of biocompatible materials for tissue...

Advanced image segmentation and processing tools present an opportunity to study cell processes and their dynamics. However, image analysis is often routine and time-consuming. Nowadays, alternative data-driven approaches using deep learning are potentially offering automatized, accurate, and fast image analysis. In this paper, we extend the applic...

The composition of fatty acids of lipids and the ability of cyanobacteria to synthesize degradable polyhydroxyalkanoates (PHA) were examined in previously unstudied cyanobacteria isolated from a number of water bodies of the Yenisei River Basin. Ten strains of various species belonging to the orders Chroococcales, Oscillatoriales, Nostocales and Le...

Background and purpose Cyclophosphamide (CP) is a widely used antitumor and immunosuppressive drug, but it is highly cytotoxic and has carcinogenic and teratogenic potential. To reduce adverse effects of CP therapy and the frequency of its administration, the microencapsulation of CP into biodegradable polymeric matrices can be performed. However,...

In this work, for the first time, films were obtained based on biodegradable polyhydroxyalkanoates (PHAs) - a copolymer of 3-hydroxybutyrate-co-3-hydroxyvalerate P(3HB-co-3HV) and a copolymer of 3-hydroxybutyrate-co-4-hydroxybutyrate P(3HB-co-4HB), containing drugs of different chemical structure and action - antibiotics (ceftazidime, doripenem), a...

Polyhydroxyalkanoates (PHAs) are used for various biomedical applications due to their biocompatibility. Surface properties, such as surface roughness, are crucial for PHAs performance. Traditional parameters used for the characterization of surface roughness, such as Ra, are often insufficient to capture the complex and hierarchical (multiscale) t...

It has been established that the wild-type Cupriavidus necator B-10646 strain uses saturated fatty acids (SFAs) for growth and polyhydroxyalkanoate (PHA) synthesis. It uses lauric (12:0), myristic (14:0), palmitic (16:0) and stearic (18:0) acids as carbon sources; moreover, the elongation of the C-chain negatively affects the biomass and PHA yields...

Surface of polyhydroxyalkanoate (PHA) films of varying monomer compositions are analyzed using atomic force microscopy (AFM) and unsupervised machine learning (ML) algorithms to investigate and classify films based on global attributes such as the scan size, film thickness, and monomer type. The experiment provides benchmarked results for 12 of the...

In the original publication [...]

Fungicides reduce the risk of mycopathologies and reduce the content of mycotoxins in commercial grain. The effect of fungicides on the structural and functional status of the root system of grain crops has not been studied enough. In this regard, we studied the phytocytotoxic effects tebuconazole (TEB) and epoxiconazole (EPO) and azoxystrobin (AZO...

The article presents the results of a study on the possibility of synthesizing biodegradable poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] from renewable waste fish oil (WFO) by the Cupriavidus necator B-10646 bacterium. For the first time, waste oil generated during the processing of Sprattus balticus in the production of sprats was...

The development of controlled drug delivery systems, in the form of microparticles, is an important area of experimental pharmacology. The success of the design and the quality of the obtained microparticles are determined by the method of manufacture and the properties of the material used as a carrier. The goal is to obtain and characterize micro...

The synthesis of PHA was first investigated using WFOs obtained from smoked-sprat heads, substandard fresh sprats, and fresh mackerel heads and backbones. All the WFOs ensured the growth of the wild-type strain Cupriavidus necator B-10646 and the synthesis of PHA, regardless of the degree of lipid saturation (from 0.52 to 0.65) and the set and rati...

The properties, features of thermal behavior and crystallization of copolymers containing various types of valerate monomers were studied depending on the set and ratio of monomers. We synthesized and studied the properties of three-component copolymers containing unusual monomers 4-hydroxyvalerate (4HV) and 3-hydroxy-4-methylvalerate (3H4MV), in a...

The results of constructing 3D scaffolds from degradable poly(3-hydrosbutyrpate-co-3-hydroxyvalerate) using FDM technology and studying the structure, mechanical properties, biocompatibility in vitro, and osteoplastic properties in vivo are presented. In the process of obtaining granules, filaments, and scaffolds from the initial polymer material,...

Biodegradable polyhydroxyalkanoates, biopolymers of microbiological origin, formed by 3- and 4-hydroxybutyrate monomers P(3HB-co-4HB), were used to obtain nanomembranes loaded with drugs as cell carriers by electrospinning. Resorbable non-woven membranes from P(3HB-co-4HB) loaded with ceftazidime, doripinem, and actovegin have been obtained. The lo...

The waste fish oil obtained from Baltic sprat waste in the production of canned sprats was studied as a sole carbon substrate for PHA synthesis by the wild-type strain Cupriavidus necator B-10646. Sprat oil contained a set of fatty acids with a chain length from C14 to C24, saturation factor 0.63, and provided bacterial growth and PHA synthesis. Ba...

The properties of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) P(3HB-co-3HHx) copolymers with different ratios of monomers synthesized by the wild-type strain Cupriavidus necator B-10646 on sugars, and an industrial sample from Kaneka synthesized by the recombinant strain C. necator NSDG-ΔfadB1 on soybean oil, were studied in a comparative aspect...

The study addresses the growth of the new wild-type strain Cupriavidus necator IBP/SFU-1 and the synthesis of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-co-4HB) on media containing fructose and three different precursors of 4HB (ε-caprolactone 1,4-butanediol and 1,6-hexanediol). It was found that ε-caprolactone is the best precursor for th...

In this work, polyhydroxyalkanoates-based microparticles containing antibacterial drug rifampicin were obtained. The main characteristics of the microparticles were investigated: the particles yield, encapsulation efficiency and drug loading, average radius, surface morphology, polydispersity index, zeta potential and cytotoxicity towards HeLa cell...

The study addresses the growth of the wild-type strain Cupriavidus necator B-10646 and the synthesis of sulfur-containing polyhydroxyalkanoates (PHA) by this strain on media containing fructose and three different precursors (3-mercaptopropionic acid, 3′,3′-dithiodipropionic acid and 3′,3′-thiodipropionic acid). By varying the concentration and num...

The needs of modern regenerative medicine for biodegradable polymers are wide and varied. Restoration of the viability of the vascular tree is one of the most important components of the preservation of the usefulness of organs and tissues. The creation of vascular implants compatible with blood is an important task of vascular bioengineering. The...

The results of surface modification of solvent casting films made from polyhydroxyalkanoates (PHAs) of various compositions are presented: homopolymer poly-3-hydroxybutyrate P(3HB) and copolymers comprising various combinations of 3-hydroxybutyrate (3HB), 3-hydroxyvalerate (3HV), 4-hydroxybutyrate(4HB), and 3-hydroxyhexanoate (3HHx) monomers treate...

From a series of biodegradable natural polymers of polyhydroxyalkanoates (PHAs)—poly-3-hydroxybutyrate (P(3HB) and copolymers containing, in addition to 3HB monomers, monomers of 3-hydroxyvalerate (3HV), 3-hydroxyhexanoate (3HHx), and 4-hydroxybutyrate (4HB), with different ratios of monomers poured—solvent casting films and nanomembranes with orie...

Synthesis of P(3HB-co-3HV-co-4HV) copolymers by the wild-type strain Cupriavidus necator B-10646 on fructose or sodium butyrate as the main C-substrate with the addition of γ-valerolactone as a precursor of 3HV and 4HV monomers was studied. Bacterial cells were cultivated in the modes that enabled production of a series of copolymers with molar fra...

Three-component slow-release fungicide formulations with different modes of action of the active ingredients for suppressing potato pathogens were constructed for the first time. The difenoconazole, mefenoxam, prothioconazole, and azoxystrobin fungicides were embedded in the degradable polymer P(3HB)/birch wood flour blend and examined using SEM, I...

The objective of this study was to produce and characterize collagen conjugated poly(3-hydroxybutyrate) (P3HB) microparticles. The double emulsion solvent evaporation technique was used to fabricate biopolymer microparticles. Alkaline hydrolysis method was used for carboxylation of P3HB microparticles followed by collagen (type I) conjugation using...

Phytotoxicity, cytotoxicity and genotoxicity of pesticides with various mechanisms of targeted activity were studied in a hydroponic culture of 2-day-old seedlings of Triticum aestivum. All studied pesticides (with the exception of metribuzin) exhibited dose-dependent phytotoxicity (inhibited the growth of the main root and reduced the yield of roo...

To increase the availability and expand the raw material base, the production of polyhydroxyalkanoates (PHA) by the wild strain Cupriavidus necator B-10646 on hydrolysates of sugar beet molasses was studied. The hydrolysis of molasses was carried out using β-fructofuranosidase, which provides a high conversion of sucrose (88.9%) to hexoses. We show...

The efficacy of slow-release formulations of tribenuron-methyl (TBM) embedded in the matrix of degradable poly(3-hydroxybutyrate) blended with birch wood flour [polymer/wood flour/herbicide 50/30/20 wt.%] was compared with the efficacy of TBM as the active ingredient of the Mortira commercial formulation, which was applied as post-emergence spray t...

In this work, delivery systems in the form of microparticles and films containing 1,2,4-trioxolane (ozonide, OZ) based on polyhydroxyalkanoates (PHAs) were developed. Main systems’ characteristics were investigated: the particle yield, average diameter, zeta potential, surface morphology, loading capacity, and drug release profile of microparticles...

The synthesis of bacterial cellulose (BC) by Komagataeibacter xylinus strain B-12068 was investigated on various C-substrates, under submerged conditions with stirring and in static surface cultures. We implemented the synthesis of BC on glycerol, glucose, beet molasses, sprat oil, and a mixture of glucose with sunflower oil. The most productive pr...

The diversity of the forms of living matter and the new knowledge in physics and chemistry of living systems have provided the basis for constructing biological systems of different complexity and arrangements in order to synthesize a wide range of macromolecules. Microorganisms are a source for producing various foodstuffs as well as medical and t...

The wide use of pesticides in agriculture has caused uncontrolled distribution of these chemicals in the environment, calling for the development and investigation of new environmentally friendly formulations, which would reduce human impact on nature. In the present study, the metribuzin (MET), tribenuron‐methyl (TBM), and fenoxaprop‐P‐ethyl (FPE)...

The bacterial strain isolated from soil was identified as Cupriavidus necator IBP/SFU-1 and investigated as a PHA producer. The strain was found to be able to grow and synthesize PHAs under autotrophic conditions and showed a broad organotrophic potential towards different carbon sources: sugars, glycerol, fatty acids, and plant oils. The highest c...

The study reports results of using a CO2-laser in continuous wave (3 W; 2 m/s) and quasi-pulsed (13.5 W; 1 m/s) modes to treat films prepared by solvent casting technique from four types of polyhydroxyalkanoates (PHAs), namely poly-3-hydroxybutyrate and three copolymers of 3-hydroxybutyrate: with 4-hydroxybutyrate, 3-hydroxyvalerate, and 3-hydroxyh...

Purpose To synthesize and investigate polyhydroxyalkanoates (PHAs) with different monomer composition and percentages and polymer films prepared from them. Results Various PHAs: homopolymer poly-3-hydroxybutyrate P(3HB) and 2-, 3-, and 4-component copolymers comprising various combinations of 3-hydroxybutyrate (3HB), 3-hydroxyvalerate (3HV), 4-hyd...

Films were prepared from 2% solutions of biodegradable poly-3-hydroxybutyrate [P(3HB)] and investigated. The polymer was synthesized by the Cupriavidus necator B-10646 bacterium cultivated using various carbon sources (glucose and glycerol of different degrees of purity, containing 0.3 to 17.93% impurities). Glycerol as the substrate influenced mol...

Two approaches have been investigated in order to reduce the cost and increase the availability of the use of biodegradable polymers of microbiological origin (polyhydroxyalkanoates, PHA): (1) expanding the raw material base and attracting glycerol as a carbon substrate (large-tonnage waste from the production of biodiesel); and (2) filling the pol...

The herbicidal activity of long-acting formulations of metribuzin and tribenuron methyl herbicides embedded in granules prepared from a mixture of degradable poly(3-hydroxybutyrate) and birch wood flour was studied in laboratory-grown weeds of various species and in wheat Triticum aestivum and barley Hordeum vulgare stands infested by weeds. The co...

Using the example of 2-day-old Triticum aestivum seedlings, grown in hydroponic culture, the cytological effects of pesticides with various mechanisms of the damaging were studied: the herbicides metribuzin, tribenuron-methyl, fenoxaprop-P-ethyl and the fungicides tebuconazole, epoxiconazole, and azoxystrobin. All pesticides showed a dose-dependent...

Polymer wound dressings based on bacterial cellulose, including those loaded with antibacterial drugs and silver nanoparticles, were produced and comprehensively studied. Regenerative properties of the experimental wound dressings were tested using laboratory animals with model defects of suppurating wounds and third-degree skin burns.

The report presents the results on destructible biocompatible biopolymers of microbiological origin - polyhydroxyalkaneotam, including synthesis, properties of the obtained polymer products and the results of biomedical research.

The effect of surface relief profiles of alkanoate-based bionanofilms to the monocyte-macrophages (MN-MPhs) from peripheral blood of patients with atherosclerosis was studied in vitro. Patients were subjected to coronary stenting. Cell morphology and phenotype (expression of CD antigens, levels of production of marker cytokines) in vitro were analy...

BACKGROUND The purpose of the present study was to develop ecofriendly herbicide formulations. Its main aim was to develop and investigate slow‐release formulations of herbicides (metribuzin, tribenuron‐methyl, and fenoxaprop‐P‐ethyl) of different structure, solubility, and specificity, which were loaded into a degradable matrix of poly‐3‐hydroxybu...

Four PHA types were synthesized in the culture of Cupriavidus eutrophus B-10646 under special conditions, poly(3‑hydroxybutyrate) [P(3HB)] and of copolymers, which contained 3HB monomers and 4‑hydroxybutyrate (4HB), 3‑hydroxyvalerate (3HV), or 3‑hydroxyhexanoate (3HHx). All copolymers had the Mw of about 550-670 kDa, and the homopolymer P(3HB) had...

Slow-release fungicide formulations (azoxystrobin, epoxiconazole, and tebuconazole) shaped as pellets and granules in a matrix of biodegradable poly(3-hydroxybutyrate) and natural fillers (clay, wood flour, and peat) were constructed. IR spectroscopy showed no formation of chemical bonds between components in the experimental formulations. The form...

The synthesis of polyhydroxyalkanoates (PHAs) was scaled up to pilot production in a 150-L fermenter on sugars (fructose and glucose) and purified and crude glycerol in a culture of the wild-type strain Cupriavidus necator B-10646. Over 60 h of cultivation, a cell concentration of 150-160 g/L was obtained on purified glycerol and glucose; cultivati...

Hybrid wound dressings have been constructed using two biomaterials: bacterial cellulose (BC) and copolymer of 3-hydroxybutyric and 4-hydroxybutyric acids [P(3HB/4HB)] – a biodegradable polymer of microbial origin. Some of the experimental membranes were loaded with drugs promoting wound healing and epidermal cells differentiated from multipotent a...

The present study addresses the synthesis and properties of polyhydroxyalkanoates (PHA) of different composition synthesized by Cupriavidus eutrophus B-10646 using glycerol as a carbon substrate. Poly(3-hydroxybutyrate) [P(3HB)] was effectively synthesized in fed-batch culture in a 30-L fermenter on glycerol of various purification degrees, with 99...

The morphotypes of human macrophages (MPh) were studied in the culture on nano-structured biopolymer substrates, made from polyhydroxyalcanoates (PHAs) of five various monomer compositions, followed by the solvent evaporation. Its surface relief, which was further in direct contact with human cells in vitro, was analyzed by atomic force microscopy...

In this study, polymer-based microparticles are used to improve the therapeutic properties of ceftriaxone (CEF) and render them safer. Poly-3-hydroxybutyrate (P3HB) and poly-3-hydroxybutyrate/polyethylene glycol (P3HB-PEG)-based microparticles were prepared by two methods: a double emulsification technique and spray-drying. The microparticles were...

A strain of acetic acid bacteria, Komagataeibacter xylinus B-12068, was studied as a source for bacterial cellulose (BC) production. The effects of cultivation conditions (carbon sources, temperature, and pH) on BC production and properties were studied in surface and submerged cultures. Glucose was found to be the best substrate for BC production...

The study investigates toxic effects of the fungicide tebuconazole (TEB) on Fusarium-infected wheat (Triticum aestivum) plants based on the morphological characteristics of root apices and changes in the integrated parameters of redox homeostasis, including the contents of free proline and products of peroxidation of proteins (carbonylated proteins...

BACKGROUND Polyhydroxyalkanoates (PHA) containing 3‐hydroxy‐4‐methylvalerate (3H4MV) have better processing properties than other PHA types and were not prone to ageing. The main challenge in the production of these polymers is to simultaneously achieve high cell biomass, high polymer content, and high molar fraction of 3H4MV. The aim of this study...

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) belong to an important therapeutic class for treatment of type 2 diabetes. Six GLP-1 RAs, each utilizing a unique drug delivery strategy, are now approved by the Food and Drug Administration (FDA) and additional, novel GLP-1 RAs are still under development, making for a crowded marketplace and f...

Composites of bacterial cellulose, which were synthesized in a culture of the strain of acetic acid bacteria Komagataeibacter xylinus VKPM B-12068, with silver nanoparticles were produced hydrothermally by varying the concentrations of AgNO3 in the medium. The presence of silver in the composites was confirmed by elemental analysis. An increase in...

The present study describes production of bacterial cellulose composites with silver nanoparticles and antibiotics and compares their properties. Bacterial cellulose (BC) composites synthesized in the culture of the strain of acetic acid bacterium Komagataeibacter xylinus VKPM B-12068 with silver nanoparticles, BC/AgNps, were produced hydrothermall...

The present study investigates physicochemical, mechanical, and biological properties of polyhydroxyalkanoate (PHA) copolymers containing 4-hydroxybutyrate (4HB) synthesized in Cupriavidus eutrophus B10646 culture. In poly(3-hydroxybutyrate/4-hydroxybutyrate) [P(3HB/4HB)] bipolymers, 4HB varied between 10.4 and 75.0 mol%; in poly(3-hydroxybutyrate/...

As intracellular carbon and energy storage materials, polyhydroxyalkanoates (PHA) are a diverse biopolyesters synthesized by many bacteria. PHA have been produced in large quantity for various application research including medical implants for approximately 30. years. Many studies demonstrated that PHA are promising implant materials due to their...