Papers by Mariia S. Saveleva
Macromolecular Bioscience, 2021
In current orthopedic practice, bone implants used to-date often exhibit poor osteointegration, i... more In current orthopedic practice, bone implants used to-date often exhibit poor osteointegration, impaired osteogenesis, and, eventually, implant failure. Actively pursued strategies for tissue engineering could overcome these shortcomings by developing new hybrid materials with bioinspired structure and enhanced regenerative potential. In this study, the osteogenic and therapeutic potential of bioactive vaterite is investigated as a functional component of a fibrous polymeric scaffold for bone regeneration. Hybrid two-layered polycaprolactone scaffolds coated with vaterite (PCL/CaCO 3) are studied during their 28-days implantation period in a rat femur defect. After this period, the study of tissue formation in the defected area is performed by the histological study of femur cross-sections. Immobilization of alkaline phosphatase (ALP) into PCL/CaCO 3 scaffolds accelerates new bone tissue formation and defect repair. PCL/CaCO 3 and PCL/CaCO 3 /ALP scaffolds reveal 37.3% and 62.9% areas, respectively, filled with newly formed bone tissue in cross-sections compared to unmineralized PCL scaffold (17.5%). Bone turnover markers are monitored on the 7th and 28th days after implantation and reveal an increase of osteocalcin level for both PCL/CaCO 3 and PCL/CaCO 3 /ALP compared with PCL indicating the activation of osteogenesis. These findings indicate that vaterite, as an osteoconductive component of polymeric scaffolds, promotes osteogenesis, supports angiogenesis, and facilitates bone defect repair.
Microvascular Research, 2021
The investigations of angiotropic effects of liraglutide are an issue of significant scientific a... more The investigations of angiotropic effects of liraglutide are an issue of significant scientific and practical interest. The successful application of liraglutide has been shown in glycemic control in patients with the type 2 diabetes mellitus (DM), but the effect of liraglutide in patients with type 1 DM has not been completely studied yet in clinical practice. Therefore, the present study is aimed to investigate the effect of liraglutide which is agonist of glucagon-like peptide-1 receptors, on microcirculation in white outbred rats with the alloxaninduced diabetes. Materials and methods: The study was performed with 70 white outbred rats, divided into 4 groups: 1) control group (intact animals (Control)); 2) comparison group (diabetes mellitus (DM))-animals with the alloxaninduced diabetes; 3) experimental group no. 1 (liraglutide low dose (LLD))-animals with the alloxaninduced diabetes, which were injected by liraglutide at dosage of 0.2 mg/kg of animal weight per a day; 4) experimental group no. 2 (liraglutide high dose (LHD))-animals with the alloxan-induced diabetes, which were injected by liraglutide at dosage of 0.4 mg/kg of animal weight per a day. The carbohydrate metabolism disorders, the microcirculation of posterior paw skin, as well as the concentration of catecholamines and markers of endothelial alteration in blood were estimated at the 42nd day of the experiment in the comparison and experimental groups. Results: It was found that the correction of carbohydrate metabolism by liraglutide is succeeded by the normalization of skin perfusion of posterior paw skin of the experimental animals. Recovery of microcirculation is associated with a decrease in vascular tone and stimulation of endothelium-dependent vasodilation, caused by simultaneous decrease of catecholamines, endothelin-1 and asymmetric dimethylarginine (ADMA) concentrations in blood serum. At the same time, the administration of liraglutide on the background of insulin-deficiency results in decrease of endothelial cell alteration markers concentration in blood, such as sE-selectin, syndecan-1, and vascular endothelial growth factor (VEGF). Conclusion: Administration of liraglutide leads to the normalization of the carbohydrate metabolism simultaneously with the correction of microcirculation in rats with the absolute insulin deficiency. The demonstrated recovery of microcirculation by liraglutide, which represents an analogue of glucagon-like peptide-1, provides new prospects for its approval as a potential drug for pathogenetic correction of microcirculatory disorders in patients with the type 1 DM.
Frontiers in Chemistry, 2020
Surface-enhanced Raman scattering (SERS) is a high-performance technique allowing detection of ex... more Surface-enhanced Raman scattering (SERS) is a high-performance technique allowing detection of extremely low concentrations of analytes. For such applications, fibrous polymeric matrices decorated with plasmonic metal nanostructures can be used as flexible SERS substrates for analysis of analytes in many application. In this study, a three-dimensional SERS substrate consisting of a CaCO 3-mineralized electrospun (ES) polycaprolactone (PCL) fibrous matrix decorated with silver (Ag) nanoparticles is developed. Such modification of the fibrous substrate allows achieving a significant increase of the SERS signal amplification. Functionalization of fibers by porous CaCO 3 (vaterite) and Ag nanoparticles provides an effective approach of selective adsorption of biomolecules and their precise detection by SERS. This new SERS substrate represents a promising biosensor platform with selectivity to low and high molecular weight molecules.
BioNanoScience, 2019
At the present day, the biocompatibility assessment of tissue engineering scaffolds and implants ... more At the present day, the biocompatibility assessment of tissue engineering scaffolds and implants is an important issue in regenerative medicine. The present study aims to defining changes of skin microcirculation parameters in the area above scaffold implantation and using them as the criteria of dynamic estimation of biocompatibility. The experiment was performed and statistically approved with 45 white rats. The animals were exposed to subcutaneous scaffold implantation with both biocompatible and non-biocompatible scaffolds (polycaprolactone scaffolds and polycaprolactone scaffolds with adsorbed foreign protein respectively). Skin microcirculation changes in the above-scaffold area were estimated using Laser Doppler flowmetry. The investigation of morphological changes occurred after the implantation was also performed. It has been found that the dynamics of microcirculatory changes correlate with the intensity of the inflammatory reaction occurring in the tissues after scaffold implantation. These facts substantiate the use of tissue perfusion as the criteria of scaffold biocompatibility assessment in subcutaneous implantation tests. The potential and future prospects of non-invasive assessment of biocompatibility by Laser Doppler flowmetry for the optimization of scaffold biocompatibility assessment in subcutaneous implantation tests have received detailed explanation.
Journal of Materials Chemistry B, 2019
Modification of titanium (Ti) bone implant materials with hybrid organic-inorganic coatings is a ... more Modification of titanium (Ti) bone implant materials with hybrid organic-inorganic coatings is a novel promising approach to improve the osteoconductivity and osteointegration of implants and prevent their failure after implantation. However, in these coatings, which are mostly hydrophilic, chemically active moieties capable of releasing oxidizing ions can have a significant influence on the corrosion resistance of Ti, which is critical for the Ti implant osteointegration behavior. In this research, in order to study the dependence of the change of the corrosion behavior of Ti on the composition of the coating, Ti surfaces were modified with various coatings: organic (alginate hydrogel crosslinked with Ca 2+ ions (Alg), and dextran sulfate (DS)), inorganic (porous calcium carbonate CaCO 3), and composite organicinorganic (Alg-CaCO 3 , DS-CaCO 3). The morphology and composition of these materials before and after the corrosion experiment, performed in simulated body fluid (SBF), were followed by extensive characterization. Electrochemical impedance spectroscopy (EIS) was performed to study the corrosion behavior of the prepared materials in SBF. The characteristics obtained during the EIS measurements revealed the dependence of the variation of the corrosion resistance level on the composition of the coating. The bare Ti surface had the higher value of the total impedance compared with the modified surfaces, while the Ti surfaces modified with organic coatings demonstrated the best charge transfer resistance in comparison with the coatings containing the inorganic CaCO 3 component and uncoated Ti.
ACS Appl. Mater. Interfaces, 2017
We have designed multifunctional silver alginate hydrogel microcontainers referred to as loaded m... more We have designed multifunctional silver alginate hydrogel microcontainers referred to as loaded microcapsules with different sizes by assembling them via a template assisted approach using natural, highly porous calcium carbonate cores. Sodium alginate was immobilized into the pores of calcium carbonate particles of different sizes followed by cross-linking via addition of silver ions, which had a dual purpose: on one hand, the were used as a cross-linking agent, albeit in the monovalent form, while on the other hand they have led to formation of silver nanoparticles. Monovalent silver ions, an unusual cross-linking agent, improve the sensitivity to ultrasound, lead to homogeneous distribution of silver nanoparticles. Silver nanoparticles appeared on the shell of the alginate microcapsules in the twin-structure as determined by transmission electron microscopy. Remote release of a payload from alginate containers by ultrasound was found to strongly depend on the particle size. The possibility to use such particles as a platform for label-free molecule detection based on the surface enhanced Raman scattering was demonstrated. Cytotoxicity and cell uptake studies conducted in this work have revealed that microcontainers exhibit nonessential level of toxicity with an efficient uptake of cells. The above-described functionalities constitute building blocks of a theranostic system, where detection and remote release can be achieved with the same carrier.
Frontiers in Chemistry, 2019
Hybrid materials, or hybrids incorporating both organic and inorganic constituents, are emerging ... more Hybrid materials, or hybrids incorporating both organic and inorganic constituents, are emerging as a very potent and promising class of materials due to the diverse, but complementary nature of the properties inherent of these different classes of materials. The complementarity leads to a perfect synergy of properties of desired material and eventually an end-product. The diversity of resultant properties and materials used in the construction of hybrids, leads to a very broad range of application areas generated by engaging very different research communities. We provide here a general classification of hybrid materials, wherein organics-in-inorganics (inorganic materials modified by organic moieties) are distinguished from inorganics-in-organics (organic materials or matrices modified by inorganic constituents). In the former area, the surface functionalization of colloids is distinguished as a stand-alone sub-area. The latter area-functionalization of organic materials by inorganic additives-is the focus of the current review. Inorganic constituents, often in the form of small particles or structures, are made of minerals, clays, semiconductors, metals, carbons, and ceramics. They are shown to be incorporated into organic matrices, which can be distinguished as two classes: chemical and biological. Chemical organic matrices include coatings, vehicles and capsules assembled into: hydrogels, layer-by-layer assembly, polymer brushes, block co-polymers and other assemblies. Biological organic matrices encompass bio-molecules (lipids, polysaccharides, proteins and enzymes, and nucleic acids) as well as higher level organisms: cells, bacteria, and microorganisms. In addition to providing details of the above classification and analysis of the composition of hybrids, we also highlight some antagonistic yin-&-yang properties of organic and inorganic materials, review applications and provide an outlook to emerging trends.
Bulletin of Experimental Biology and Medicine, 2019
We studied the particularities of osteo-and angiogenesis in albino rats after implantation of pol... more We studied the particularities of osteo-and angiogenesis in albino rats after implantation of polycaprolactone scaffolds mineralized with vaterite with adsorbed tannic acid in the femoral bone defect. It was found that the processes of angio-and osteogenesis in the bone tissue after scaffolds implantation depend on their biocompatibility. Implantation of non-biocompatible scaffolds was followed by activation of angio-and osteogenesis aimed at separation of these scaffold from surrounding tissues. Implantation of polycaprolactone/vaterite scaffolds containing tannic acid stimulated angio-and osteogenesis leading to vascularization and bone tissue formation in the matrix. This demonstrate prospects of clinical approbation of these scaffolds for stimulation of bone regeneration in traumatological and orthopedic patients.
Advanced Materials Interfaces
Novel bone growth-stimulating interfaces are designed via surface modification of titanium (Ti) s... more Novel bone growth-stimulating interfaces are designed via surface modification of titanium (Ti) surfaces using the bioceramic CaCO3 in the vaterite phase, Ca-crosslinked alginate hydrogel, or a blend of these two materials with an active enzyme, alkaline phosphatase (ALP), as an osteoinductive component. The surface morphology and chemistry of the engineered surfaces are investigated using scanning electron microscopy, atomic force microscopy, and Fourier transforms infrared spectroscopy, while the vaterite crystal fraction within the inorganic phase of the different coating types is determined by X-ray diffraction. The functionality of the osteoconductive assembled bioceramic–hydrogel interface on Ti surface in regard with an active ALP payload is verified by the surface ALP loading and its activity. The methods of loading of ALP onto a Ti surface, adsorption versus coprecipitation, have a significant influence on the activity of immobilized ALP amount. The osteoblasts cultivated on the engineered surfaces functionalized with ALP exhibit a higher viability. The proposed composite materials with an active surface and a high mineral content represent an attractive biointerface for tissue engineering.
Designing advanced biomaterials for tissue regeneration with drug delivery and release functional... more Designing advanced biomaterials for tissue regeneration with drug delivery and release functionalities remains a challenge in regenerative medicine. In this research, we have developed novel composite scaffolds based on polymeric polycaprolactone fibers coated with porous calcium carbonate structures (PCL/CaCO3) for tissue engineering and have shown their drug delivery and release in rats. In vivo biocompatibility tests of PCL/CaCO3 scaffolds were complemented with in vivo drug release study, where tannic acid (TA) was used as a model drug. Release of TA from the scaffolds was realized by recrystallization of the porous vaterite phase of calcium carbonate into the crystalline calcite. Cell colonization and tissue vascularization as well as transplantability of developed PCL/CaCO3 + TA scaffolds were observed. Detailed study of scaffold transformations during 21-day implantation period was followed by scanning electron microscopy and X-ray diffraction studies before and after in vivo implantation. The presented results demonstrate that PCL/CaCO3 scaffolds are attractive candidates for implants in bone regeneration and tissue engineering with a possibility of loading biologically active molecules and controlled release.
Membranes are important components in a number of systems, where separation and control of the fl... more Membranes are important components in a number of systems, where separation and control of the flow of molecules is desirable. Controllable membranes represent an even more coveted and desirable entity and their development is considered to be the next step of development. Typically, membranes are considered on flat surfaces, but spherical capsules possess a perfect " infinite " or fully suspended membranes. Similarities and transitions between spherical and flat membranes are discussed, while applications of membranes are also emphasized.
The process of porous calcium carbonate (CaCO 3) covering on electrospun poly(e-caprolactone) (PC... more The process of porous calcium carbonate (CaCO 3) covering on electrospun poly(e-caprolactone) (PCL) fibers is described in this study. Uniform CaCO 3 coatings, composed of vaterite microparticles and its aggregates, were formed on PCL fibers by mineral precipitation from solution under ultrasonic treatment. The porous structure of CaCO 3 in vater-ite polymorphic form is useful for loading of various substances (drugs and nanoparticles), and this property makes vaterite an appropriate material for design of drug delivery systems. Such mineralization was implemented to attain therapeutic and/or biological activity of tissue engineering scaffolds based on electrospun PCL, by means of CaCO 3 coatings. Various structures and polymorphs of CaCO 3 coatings were obtained by variation of growth conditions (time of fiber incubation in work solution, ultrasonic treatment of this system). Coating homogeneity, CaCO 3 polymorphic form, morphology, and CaCO 3 mass can be controlled by number of successive stages of fibrous material treatment. Cytotoxicity tests showed that PCL fibers mineralized with CaCO 3 did not release substances toxic for cells. SEM images of PCL/CaCO 3 scaffolds cultured with cells demonstrate that scaffolds supported cell adhesion and spreading. The presented results show the new technique of controlled PCL scaffold mineralization with vaterite, and an opportunity of using PCL/CaCO 3 as scaffolds for tissue engineering. V C 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 00A:000–000, 2016.
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Papers by Mariia S. Saveleva