Yuliya Safarova

Scopus Publications

Magnetron Sputtering of Antibacterial and Antifungal Tantalum-Copper and Niobium-Copper Coatings on Three Dimensional-Printed Porous Titanium Alloy Scaffolds: Part II
Bagdat Azamatov, Dmitry Dogadkin, Bauyrzhan Maratuly, Alexandr Borisov, Yuliya Safarova (Yantsen), Ridvan Yamanoglu, and Darya Alontseva
Johnson Matthey
This is Part II of a study on the antimicrobial efficacy of tantalum-copper and niobium-copper coatings, applied via magnetron sputtering (MS) on three dimensional (3D) printed porous Ti6Al4V alloy scaffolds and gas-abrasive treated Ti6Al4V alloy, against Staphylococcus aureus and Candida albicans. Thicker coatings were found to show superior antimicrobial activity; however, thin niobium-copper coatings and uncoated alloy did not exhibit inhibitory effects. The release dynamics of copper ions from tantalum-copper coatings into physiological solution, analysed over ten days via inductively coupled plasma mass spectrometry, matched the inhibition zone growth. These findings support the potential of these coatings in developing endoprosthesis implants with enhanced antimicrobial properties.

Microplasma-Sprayed Titanium and Hydroxyapatite Coatings on Ti6Al4V Alloy: in vitro Biocompatibility and Corrosion Resistance: Part I
Darya Alontseva, Yuliya Safarova (Yantsen), Sergii Voinarovych, Aleksei Obrosov, Ridvan Yamanoglu, Fuad Khoshnaw, Assem Nessipbekova, Aizhan Syzdykova, Hasan Ismail Yavuz, Sergii Kaliuzhnyi,et al.
Johnson Matthey
This two-part paper investigates the bioactivity and mechanical properties of coatings applied to Ti6Al4V, a common titanium alloy used in endoprosthetic implants. Coatings made from hydroxyapatite (HA) powder and commercially pure titanium (CP-Ti) wires were applied using microplasma spraying. The study focuses on the responses of rat mesenchymal stem cells (MSCs), which are essential for bone healing, to these coatings. Part I shows how adjusting the microplasma spraying process allows coatings with varying porosity and surface roughness to be achieved.

Magnetron Sputtering of Antibacterial and Antifungal Tantalum-Copper and Niobium-Copper Coatings on Three Dimensional-Printed Porous Titanium Alloy Scaffolds: Part I
Bagdat Azamatov, Alexandr Borisov, Bauyrzhan Maratuly, Dmitry Dogadkin, Yuliya Safarova (Yantsen), Ridvan Yamanoglu, and Darya Alontseva
Johnson Matthey
This two-part study evaluates the antimicrobial efficacy of tantalum-copper and niobium-copper coatings, applied via magnetron sputtering (MS) on three dimensional (3D) printed porous Ti6Al4V (Ti-64) alloy scaffolds and gas-abrasive treated Ti-64 alloy, against Staphylococcus aureus and Candida albicans. Scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) analysis verified the application of coatings with 25 wt% copper, at thicknesses of 2 μm and 10 μm, to scaffolds (72% porosity) and roughened Ti-64 alloy (mean areal roughness of 4.6 ± 1 μm). The findings support the potential of these coatings in developing endoprosthesis implants with enhanced antimicrobial properties. Part I introduces the background research and describes the materials, methods and rationale for the present work.

Microplasma-Sprayed Titanium and Hydroxyapatite Coatings on Ti6Al4V Alloy: in vitro Biocompatibility and Corrosion Resistance: Part II
Darya Alontsev, Yuliya Safarova (Yantsen), Sergii Voinarovych, Aleksei Obrosov, Ridvan Yamanoglu, Fuad Khoshnaw, Assem Nessipbekova, Aizhan Syzdykova, Hasan Ismail Yavuz, Sergii Kaliuzhnyi,et al.
Johnson Matthey
Part II presents the results which show that HA coatings significantly enhance MSC proliferation by 13% compared to the titanium alloy base, while titanium coatings also exhibit an 11% increase. Porosity inversely affects CP-Ti’s elasticity. Coatings with lower porosity demonstrate better corrosion resistance. HA coatings promote osteogenic activity and angiogenesis, which is crucial for implant integration.

Unlocking Genome Editing: Advances and Obstacles in CRISPR/Cas Delivery Technologies
Bibifatima Kaupbayeva, Andrey Tsoy, Yuliya Safarova (Yantsen), Ainetta Nurmagambetova, Hironobu Murata, Krzysztof Matyjaszewski, and Sholpan Askarova
MDPI AG
CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats associated with protein 9) was first identified as a component of the bacterial adaptive immune system and subsequently engineered into a genome-editing tool. The key breakthrough in this field came with the realization that CRISPR/Cas9 could be used in mammalian cells to enable transformative genetic editing. This technology has since become a vital tool for various genetic manipulations, including gene knockouts, knock-in point mutations, and gene regulation at both transcriptional and post-transcriptional levels. CRISPR/Cas9 holds great potential in human medicine, particularly for curing genetic disorders. However, despite significant innovation and advancement in genome editing, the technology still possesses critical limitations, such as off-target effects, immunogenicity issues, ethical considerations, regulatory hurdles, and the need for efficient delivery methods. To overcome these obstacles, efforts have focused on creating more accurate and reliable Cas9 nucleases and exploring innovative delivery methods. Recently, functional biomaterials and synthetic carriers have shown great potential as effective delivery vehicles for CRISPR/Cas9 components. In this review, we attempt to provide a comprehensive survey of the existing CRISPR-Cas9 delivery strategies, including viral delivery, biomaterials-based delivery, synthetic carriers, and physical delivery techniques. We underscore the urgent need for effective delivery systems to fully unlock the power of CRISPR/Cas9 technology and realize a seamless transition from benchtop research to clinical applications.

Strontium- and Copper-Doped Ceramic Granules in Bone Regeneration-Associated Cellular Processes
Yuliya Safarova (Yantsen), Assem Nessipbekova, Aizhan Syzdykova, Farkhad Olzhayev, Bauyrzhan Umbayev, Aliya Kassenova, Inna V. Fadeeva, Sholpan Askarova, and Julietta V. Rau
MDPI AG
Background: Pathological bone fracturing is an escalating problem driven by increasing aging and obesity. Bioceramics, particularly tricalcium-phosphate-based materials (TCP), are renowned for their exceptional biocompatibility, osteoconductivity, and ability to promote biomineralization. In the present study, we designed and characterized TCP porous granules doped with strontium (Sr) and copper (Cu) (CuSr TCP). Sr2+ ions were selected as Sr plays a crucial role in early bone formation, osteogenesis, and angiogenesis; Cu2+ ions possess antibacterial properties. Materials: The synthesized CuSr TCP granules were characterized by X-ray diffraction. Cytotoxicity and cell proliferation analyses’ assays were performed through the lactate dehydrogenase (LDH) activity and CCK-8 viability tests in rat bone marrow-derived mesenchymal stem cells (BM-MSCs). Hemolytic activity was carried out with human red blood cells (RBCs). Early and late osteogenesis were assessed with alkaline phosphatase (ALP) and Alizarin Red S activity in human osteoblast progenitor cells and rat BM-MSCs. The influence of CuSr TCP on angiogenesis was investigated in human umbilical vein endothelial cells (HUVECs). Results: We have demonstrated that media enriched with CuSr TCP in concentrations ranging from 0.1 mg/mL to 1 mg/mL were not cytotoxic and did not significantly affect cell proliferation rate motility. Moreover, a concentration of 0.5 mg/mL showed a 2.5-fold increase in the migration potential of BM-MSCs. We also found that CuSr TCP-enriched media slightly increased early osteogenesis. We also found that Sr and Cu substitutions in TCP particles significantly enhanced the measured angiogenic parameters compared to control and unsubstituted TCP granules. Conclusion: Our results demonstrate that TCP porous granules doped with Sr and Cu are biocompatible, promote osteodifferentiation and angiogenesis, and could be recommended for further in vivo studies.

Biocompatibility and Corrosion of Microplasma-Sprayed Titanium and Tantalum Coatings versus Titanium Alloy
Darya Alontseva, Yuliya Safarova (Yantsen), Sergii Voinarovych, Aleksei Obrosov, Ridvan Yamanoglu, Fuad Khoshnaw, Hasan Ismail Yavuz, Assem Nessipbekova, Aizhan Syzdykova, Bagdat Azamatov,et al.
MDPI AG
This study investigates the in vitro biocompatibility, corrosion resistance, and adhesion strength of a gas abrasive-treated Ti6Al4V alloy, alongside microplasma-sprayed titanium and tantalum coatings. Employing a novel approach in selecting microplasma spray parameters, this study successfully engineers coatings with tailored porosity, roughness, and over 20% porosity with pore sizes up to 200 μm, aiming to enhance bone in-growth and implant integration. This study introduces an innovative methodology for quantifying surface roughness using laser electron microscopy and scanning electron microscopy, facilitating detailed morphological analysis of both the substrate and coatings. Extensive evaluations, including tests for in vitro biocompatibility, corrosion resistance, and adhesive strength, revealed that all three materials are biocompatible, with tantalum coatings exhibiting superior cell proliferation and osteogenic differentiation, as well as the highest corrosion resistance. Titanium coatings followed closely, demonstrating favorable osteogenic properties and enhanced roughness, which is crucial for cell behavior and attachment. These coatings also displayed superior tensile adhesive strengths (27.6 ± 0.9 MPa for Ti and 28.0 ± 4.9 MPa for Ta), surpassing the ISO 13179-1 standard and indicating a robust bond with the substrate. Our findings offer significant advancements in biomaterials for medical implants, introducing microplasma spraying as a versatile tool for customizing implant coatings, particularly emphasizing the superior performance of tantalum coatings in terms of biocompatibility, osteogenic potential, and corrosion resistance. This suggests that tantalum coatings are a promising alternative for enhancing the performance of metal implants, especially in applications demanding high biocompatibility and corrosion resistance.

The Role of Cdc42 in the Insulin and Leptin Pathways Contributing to the Development of Age-Related Obesity
Bauyrzhan Umbayev, Timur Saliev, Yuliya Safarova (Yantsen), Aislu Yermekova, Farkhad Olzhayev, Denis Bulanin, Andrey Tsoy, and Sholpan Askarova
MDPI AG
Age-related obesity significantly increases the risk of chronic diseases such as type 2 diabetes, cardiovascular diseases, hypertension, and certain cancers. The insulin–leptin axis is crucial in understanding metabolic disturbances associated with age-related obesity. Rho GTPase Cdc42 is a member of the Rho family of GTPases that participates in many cellular processes including, but not limited to, regulation of actin cytoskeleton, vesicle trafficking, cell polarity, morphology, proliferation, motility, and migration. Cdc42 functions as an integral part of regulating insulin secretion and aging. Some novel roles for Cdc42 have also been recently identified in maintaining glucose metabolism, where Cdc42 is involved in controlling blood glucose levels in metabolically active tissues, including skeletal muscle, adipose tissue, pancreas, etc., which puts this protein in line with other critical regulators of glucose metabolism. Importantly, Cdc42 plays a vital role in cellular processes associated with the insulin and leptin signaling pathways, which are integral elements involved in obesity development if misregulated. Additionally, a change in Cdc42 activity may affect senescence, thus contributing to disorders associated with aging. This review explores the complex relationships among age-associated obesity, the insulin–leptin axis, and the Cdc42 signaling pathway. This article sheds light on the vast molecular web that supports metabolic dysregulation in aging people. In addition, it also discusses the potential therapeutic implications of the Cdc42 pathway to mitigate obesity since some new data suggest that inhibition of Cdc42 using antidiabetic drugs or antioxidants may promote weight loss in overweight or obese patients.

A Brief Review of Current Trends in the Additive Manufacturing of Orthopedic Implants with Thermal Plasma-Sprayed Coatings to Improve the Implant Surface Biocompatibility
Darya Alontseva, Bagdat Azamatov, Yuliya Safarova (Yantsen), Sergii Voinarovych, and Gaukhar Nazenova
MDPI AG
The demand for orthopedic implants is increasing, driven by a rising number of young patients seeking an active lifestyle post-surgery. This has led to changes in manufacturing requirements. Joint arthroplasty operations are on the rise globally, and recovery times are being reduced by customized endoprostheses that promote better integration. Implants are primarily made from metals and ceramics such as titanium, hydroxyapatite, zirconium, and tantalum. Manufacturing processes, including additive manufacturing and thermal plasma spraying, continue to evolve. These advancements enable the production of tailored porous implants with uniform surface coatings. Coatings made of biocompatible materials are crucial to prevent degradation and enhance biocompatibility, and their composition, porosity, and roughness are actively explored through biocompatibility testing. This review article focuses on the additive manufacturing of orthopedic implants and thermal plasma spraying of biocompatible coatings, discussing their challenges and benefits based on the authors’ experience with selective laser melting and microplasma spraying of metal-ceramic coatings.

Role of a small GTPase Cdc42 in aging and age-related diseases
Bauyrzhan Umbayev, Yuliya Safarova, Aislu Yermekova, Assem Nessipbekova, Aizhan Syzdykova, and Sholpan Askarova
Springer Science and Business Media LLC

Mesenchymal stem cells coated with synthetic bone-targeting polymers enhance osteoporotic bone fracture regeneration
Yuliya Safarova (Yantsen), Farkhad Olzhayev, Bauyrzhan Umbayev, Andrey Tsoy, Gonzalo Hortelano, Tursonjan Tokay, Hironobu Murata, Alan Russell, and Sholpan Askarova
MDPI AG
Osteoporosis is a progressive skeletal disease characterized by reduced bone density leading to bone fragility and an elevated risk of bone fractures. In osteoporotic conditions, decrease in bone density happens due to the augmented osteoclastic activity and the reduced number of osteoblast progenitor cells (mesenchymal stem cells, MSCs). We investigated a new method of cell therapy with membrane-engineered MSCs to restore the osteoblast progenitor pool and to inhibit osteoclastic activity in the fractured osteoporotic bones. The primary active sites of the polymer are the N-hydroxysuccinimide and bisphosphonate groups that allow the polymer to covalently bind to the MSCs’ plasma membrane, target hydroxyapatite molecules on the bone surface and inhibit osteolysis. The therapeutic utility of the membrane-engineered MSCs was investigated in female rats with induced estrogen-dependent osteoporosis and ulnar fractures. The analysis of the bone density dynamics showed a 27.4% and 21.5% increase in bone density at 4 and 24 weeks after the osteotomy of the ulna in animals that received four transplantations of polymer-modified MSCs. The results of the intravital observations were confirmed by the post-mortem analysis of histological slices of the fracture zones. Therefore, this combined approach that involves polymer and cell transplantation shows promise and warrants further bio-safety and clinical exploration.

Mesenchymal stem cells modifications for enhanced bone targeting and bone regeneration
Yuliya Safarova, Bauyrzhan Umbayev, Gonzalo Hortelano, and Sholpan Askarova
Future Medicine Ltd
In pathological bone conditions (e.g., osteoporotic fractures or critical size bone defects), increasing the pool of osteoblast progenitor cells is a promising therapeutic approach to facilitate bone healing. Since mesenchymal stem cells (MSCs) give rise to the osteogenic lineage, a number of clinical trials investigated the potential of MSCs transplantation for bone regeneration. However, the engraftment of transplanted cells is often hindered by insufficient oxygen and nutrients supply and the tendency of MSCs to home to different sites of the body. In this review, we discuss various approaches of MSCs transplantation for bone regeneration including scaffold and hydrogel constructs, genetic modifications and surface engineering of the cell membrane aimed to improve homing and increase cell viability, proliferation and differentiation.

The Links Between the Gut Microbiome, Aging, Modern Lifestyle and Alzheimer's Disease
Sholpan Askarova, Bauyrzhan Umbayev, Abdul-Razak Masoud, Aiym Kaiyrlykyzy, Yuliya Safarova, Andrey Tsoy, Farkhad Olzhayev, and Almagul Kushugulova
Frontiers Media SA
Gut microbiome is a community of microorganisms in the gastrointestinal tract. These bacteria have a tremendous impact on the human physiology in healthy individuals and during an illness. Intestinal microbiome can influence one's health either directly by secreting biologically active substances such as vitamins, essential amino acids, lipids et cetera or indirectly by modulating metabolic processes and the immune system. In recent years considerable information has been accumulated on the relationship between gut microbiome and brain functions. Moreover, significant quantitative and qualitative changes of gut microbiome have been reported in patients with Alzheimer's disease. On the other hand, gut microbiome is highly sensitive to negative external lifestyle aspects, such as diet, sleep deprivation, circadian rhythm disturbance, chronic noise, and sedentary behavior, which are also considered as important risk factors for the development of sporadic Alzheimer's disease. In this regard, this review is focused on analyzing the links between gut microbiome, modern lifestyle, aging, and Alzheimer's disease.

Elevated levels of the small GTPase Cdc42 induces senescence in male rat mesenchymal stem cells
Bauyrzhan Umbayev, Abdul-Razak Masoud, Andrey Tsoy, Dauren Alimbetov, Farkhad Olzhayev, Alla Shramko, Aiym Kaiyrlykyzy, Yuliya Safarova, Terence Davis, and Sholpan Askarova
Springer Science and Business Media LLC

Engineering of cell membranes with a bisphosphonate-containing polymer using ATRP synthesis for bone targeting
Sonia D'Souza, Hironobu Murata, Moncy V. Jose, Sholpan Askarova, Yuliya Yantsen, Jill D. Andersen, Collin D.J. Edington, William P. Clafshenkel, Richard R. Koepsel, and Alan J. Russell
Elsevier BV

Yuliya Safarova

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Scopus Publications