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[107]
Changes in the Gut Microbiota Composition during Implantation of Composite Scaffolds Based on Poly(3-hydroxybutyrate) and Alginate on the Large-Intestine Wall
Dudun A.A., Chesnokova D.V., Voinova V.V., Bonartsev A.P., Bonartseva G.A.
Polymers.
2023,
vol. 15, № 17, 3649.
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DOI:10.3390/polym15173649
The development of biopolymer scaffolds for intestine regeneration is one of the most actively developing areas in tissue engineering. However, intestinal regenerative processes after scaffold implantation depend on the activity of the intestinal microbial community that is in close symbiosis with intestinal epithelial cells. In this work, we study the impact of different scaffolds based on biocompatible poly(3-hydroxybutyrate) (PHB) and alginate (ALG) as well as PHB/ALG scaffolds seeded with probiotic bacteria on the composition of gut microbiota of Wistar rats. Implantation of PHB/ALG scaffolds on the large-intestine wall to close its injury showed that alpha diversity of the gut microbiota was not reduced in rats implanted with different PHB/ALG scaffolds except for the PHB/ALG scaffolds with the inclusion of Lactobacillus spheres (PHB/ALG-L). The composition of the gut microbiota of rats implanted with PHB/ALG scaffolds with probiotic bacteria or in simultaneous use of an antimicrobial agent (PHB/ALG-AB) differed significantly from other experimental groups. All rats with implanted scaffolds demonstrated shifts in the composition of the gut microbiota by individual operational taxonomic units. The PHB/ALG-AB construct led to increased abundance of butyrate-producing bacteria: Ileibacterium sp. dominated in rats with implanted PHB/ALG-L and Lactobacillus sp. and Bifidobacterium sp. dominated in the control group. In addition, the PHB/ALG scaffolds had a favourable effect on the growth of commensal bacteria. Thus, the effect of implantation of the PHB/ALG scaffold compared to other scaffolds on the composition of the gut microbiota was closest to the control variant, which may demonstrate the biocompatibility of this device with the microbiota.
[106]
Poly(3-hydroxybutyrate) 3D-Scaffold–Conduit for Guided Tissue Sprouting
Zharkova I.I., Volkov A.V., Muraev A.A., Makhina T.K., Voinova V.V., Ryabova V.M., Gazhva Y.V., Kashirina A.S., Kashina A.V., Bonartseva G.A., Zhuikov V.A., Shaitan K.V., Kirpichnikov M.P., Ivanov S.Y., Bonartsev A.P.
International Journal of Molecular Sciences.
2023,
vol. 24, № 8, 6965.
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DOI: 10.3390/ijms24086965
Scaffold biocompatibility remains an urgent problem in tissue engineering. An especially interesting problem is guided cell intergrowth and tissue sprouting using a porous scaffold with a special design. Two types of structures were obtained from poly(3-hydroxybutyrate) (PHB) using a salt leaching technique. In flat scaffolds (scaffold-1), one side was more porous (pore size 100–300 µm), while the other side was smoother (pore size 10–50 µm). Such scaffolds are suitable for the in vitro cultivation of rat mesenchymal stem cells and 3T3 fibroblasts, and, upon subcutaneous implantation to older rats, they cause moderate inflammation and the formation of a fibrous capsule. Scaffold-2s are homogeneous volumetric hard sponges (pore size 30–300 µm) with more structured pores. They were suitable for the in vitro culturing of 3T3 fibroblasts. Scaffold-2s were used to manufacture a conduit from the PHB/PHBV tube with scaffold-2 as a filler. The subcutaneous implantation of such conduits to older rats resulted in gradual soft connective tissue sprouting through the filler material of the scaffold-2 without any visible inflammatory processes. Thus, scaffold-2 can be used as a guide for connective tissue sprouting. The obtained data are advanced studies for reconstructive surgery and tissue engineering application for the elderly patients.
[105]
A comprehensive study of the structure and piezoelectric response of biodegradable polyhydroxybutyrate-based films for tissue engineering applications
Chernozem R.V., Pariy I.O., Pryadko A., Bonartsev A.P., Voinova V.V., Zhuikov V.A., Makhina T.K., Bonartseva G.A., Shaitan K.V., Shvartsman V.V., Lupascu D.C., Romanyuk K.N., Kholkin A.L., Surmenev R.A., Surmeneva M.A.
Polymer Journal.
2022,
vol. 54, № 1225, 1–12.
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DOI: 10.1038/s41428-022-00662-8
The results of comprehensive research on the thermal behavior and molecular and crystalline structures of poly(3-hydroxybutyrate) (PHB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV) films of different thicknesses, their molecular weights (Mw) and 3-hydroxyvalerate (3-HV) contents are reported. Increasing film thickness from 30 to 100 μm resulted in an isotropic crystal orientation, reducing the crystallite size of the orthorhombic α-phase in the b direction from 22 to 17 nm and increasing the degree of crystallinity of the PHB films without affecting their thermal behavior. Furthermore, despite resulting in the same degree of crystallinity and roughness, an ~8-fold decrease in PHB Mw from 803 kDa to 102 kDa resulted in a decreased number of piezoactive domains. The addition of 5.9% 3-HV resulted in anisotropy in the PHB crystalline structure and increased D(020) from 19 nm to 24 nm. Additionally, a further increase in the 3-HV content to 17.5% in the PHB-HV films led to a decrease in the melting temperature and a decrease in the degree of crystallinity from 57% to 23%, which resulted in the absence of local piezoresponse. Notably, the decrease in the Mw of PHB-HV (~17%) from 1177 kDa to 756 kDa resulted in an increase in the degree of crystallinity from 23% to 32%. Moreover, the PHB-HV films became smoother with increasing 3-HV content.
[104]
Bioactive rare earth-based inorganic-organic hybrid biomaterials for wound healing and repair
Luo M., Shaitan K., Qu X., Bonartsev A.P., Lei Bo
APPLIED MATERIALS TODAY.
2022,
vol. 26, № 101304, 1–16.
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DOI: 10.1016/j.apmt.2021.101304
Rare earth-based biomaterials have representative optical/magnetic properties, which have shown the great potential in biomedical applications. In recent years, many studies have shown that rare earth-based biomaterials also possess the special biological properties, including antioxidation, antiinflammation and antibacterial activity, which also enabled their potential applications in enhancing wound healing and skin tissue regeneration. Thus, rare earth-based inorganic-organic hybrid biomaterials (REH) with special biological activities have been developed for wound healing and skin regeneration. REH biomaterials possess the double advantages of inorganic rare earth and organic biomedical polymers, and demonstrate the promising applications in wound healing and repair. In this work, we thoroughly reviewed the recent advances and findings on the fabrication and wound repair applications of bioactive REH biomaterials. The personal insights regarding as the challenges and perspectives on rare-earth nanocomposites in wound repair were also presented.
[103]
Scaffolds Based on Poly(3-Hydroxybutyrate) and Its Copolymers for Bone Tissue Engineering (Review)
Bonartsev A.P., Voinova V.V., Volkov A.V., Muraev A.A., Boyko E.M., Venediktov A.A., Didenko N.N., Dolgalev A.A.
Современные технологии в медицине.
2022,
vol. 14, № 5, 78–90.
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DOI: 10.17691/stm2022.14.5.07
Biodegradable and biocompatible polymers are actively used in tissue engineering to manufacture scaffolds. Biomedical properties of polymer scaffolds depend on the physical and chemical characteristics and biodegradation kinetics of the polymer material, 3D microstructure and topography of the scaffold surface, as well as availability of minerals, medicinal agents, and growth factors loaded into the scaffold. However, in addition to the above, the intrinsic biological activity of the polymer and its biodegradation products can also become evident. This review provides studies demonstrating that scaffolds made of poly(3-hydroxybutyrate) (PHB) and its copolymers have their own biological activity, and namely, osteoinductive properties. PHB can induce differentiation of mesenchymal stem cells in the osteogenic direction in vitro and stimulates bone tissue regeneration during the simulation of critical and non-critical bone defects in vivo.
[102]
Формирование микроструктурированных пленок поли-3-оксибутирата с регулируемой топографией поверхности
Куликовская В.И., Николайчук В.В., Бонарцев А.П., Чишанков И.Г., Акулина Е.А., Демьянова И.В., Бонарцева Г.А., Гилевская К.С., Воинова В.В.
Известия Национальной Академии наук Беларуси. Серия химических наук.
2022,
vol. 58, № 2, 135–148.
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DOI: 10.29235/1561-8331-2022-58-2-135-148
Исследована возможность формирования микроструктурированных пленок поли-3-оксибутирата методом «самоорганизации» микрокапель воды с помощью искусственных шаблонов и обратных эмульсий полимера. Установлено, что методом «самоорганизации» можно сформировать упорядоченные микроструктуры поли-3-оксибутирата с гексагональным расположением ячеек регулируемого диаметра от 1 до 4 мкм. Показано, что путем применения обратных эмульсий поли-3-оксибутирата можно получить пористые пленки с заданным размером пор от 0,4 до 3 мкм, при этом структуру пленок и размер пор в них можно регулировать путем изменения концентрации полимера в дисперсионной среде и объемного соотношения фаз. С помощью метода центрифугирования и применения искусственных шаблонов можно создавать точные реплики поли-3-оксибутирата, которые характеризуются высокой степенью однородности по всей площади и отсутствием дефектных областей. Показано, что сформированные микроструктурированные пленки поли-3-оксибутирата с регулируемой топографией поверхности перспективны для использования в качестве скаффолдов для культивирования стволовых клеток.
[101]
Обработка научно-технической информации в междисциплинарных исследованиях методами математико-лингвистического направленного поиска на примере области изучения биоматериалов для тканевой инженерии
Methods of Mathematical and Linguistic Directed Search by the Example of the Study of Biomaterials for Tissue Engineering
Antonov E., Kontsevaya Yu, Artamonov A., Orlov A., Nikolaev V., Zakharov V., Khokhlova M., Bonartsev A., Voinova V.
International Journal of Open Information Technologies.
2022,
том 10, № 11, 134–140.
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Разработка новых эффективных методов обработки научно-технической информации в междисциплинарных исследованиях с применением математико-лингвистического направленного поиска является актуальной проблемой в таких научных направлениях как изучение биоматериалов для тканевой инженерии из-за необходимости обрабатывать большие объемы информации, разнообразия источников информации и терминологической путаницы. Авторами проведено исследование по анализу входящего потока публикаций на предмет соответствия их тематическому направлению пользователя. В качестве исходного массива взята персональная база данных, собранная за 20 лет профессиональной деятельности научной группой «Медицинские биополимеры», размер которой составляет 3650 статей, который сравнивался с данными, собранными автоматизированным способом с 3-х высокорейтинговых изданий – Acta Biomaterialia, Biomaterials, Materials Today Bio. Для определения схожести текстов использовалась программная библиотека difflib, основанная на алгоритме Ратклифа–Мезнера. По итогам исследования выявлено, что разработанный подход смог адекватно выявить публикации соответствующие интересам лидера научной группы «Медицинские биополимеры», но также был выявлен ряд проблем, которые планируется решить на следующих этапах исследования.
[100]
Fabrication and characterization of a magnetic biocomposite of magnetite nanoparticles and reduced graphene oxide for biomedical applications
Mukhortova Y.R., Pryadko A.S., Chernozem R.V., Pariy I.O., Akoulina E.A., Demianova I.V., Zharkova I.I., Ivanov Y.F., Wagner D.V., Bonartsev A.P., Surmenev R.A., Surmeneva M.A.
Nano-Structures & Nano-Objects.
2022,
vol. 29, № 100843, 1–15.
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DOI: 10.1016/j.nanoso.2022.100843
Functionalization of magnetite (Fe3O4) nanoparticles with reduced graphene oxide (rGO) with the preserved magnetic properties of the former presents great potential for applying the Fe3O4/rGO biocomposite in various biomedical applications, such as magnetic resonance imaging, as a therapeutic component in initiating tumour cell death in magnetic and photon ablation therapy, and as an effective carrier for drug delivery. In this study, magnetite nanoparticles (MNPs) with a high saturation magnetization were synthesized by co-precipitation under various conditions, followed by covalent functionalization with citric acid (CA) and subsequent attachment to rGO sheets by physical adsorption. Extensive characterization revealed increasing phase purity with a subsequent decrease in the crystallite size and average size of the MNPs synthesized in an inert atmosphere compared to ambient conditions. Meanwhile, further functionalization of the MNPs with CA by covalent binding does not affect the MNP structure and size, but decreases their agglomeration. To study the magnetic properties of the MNPs and the Fe3O4/rGO composite, magnetization curves were obtained with a vibrating sample magnetometer at a pulsed magnetic field of up to 6.5 kOe. The largest values of saturation magnetization are revealed for the samples synthesized without the addition of CA in an inert atmosphere (σs = 80.27 emu/g). The addition of CA to the synthesized MNPs and Fe3O4/rGO composites reduced agglomeration, with σs values in the range from 64.10 to 60.97 emu/g. In vitro biological experiments revealed the MNP concentrations that did not cause any toxic effects on cells for use as magnetic fillers to investigate the strain-mediated effects of hybrid polymer composites on cellular behaviour due to external magnetic field exposure in the next stages of research.
[99]
Electrospun magnetic composite poly-3-hydroxybutyrate/magnetite scaffolds for biomedical applications: composition, structure, magnetic properties, and biological performance
Pryadko A.S., Mukhortova Y.R., Chernozem R.V., Pariy I., Alipkina S.I., Zharkova I.I., Dudun A.A., Zhuikov V.A., Moisenovich A.M., Bonartseva G.A., Voinova V.V., Chesnokova D.V., Ivanov A.A., Travnikova D.Y., Shaitan K.V., Bonartsev A.P., Wagner D.V., Shlapakova L.E., Surmenev R.A., Surmeneva M.A.
ACS Appl. Bio Mater.
2022,
vol. 5, № 8, 3999–4019.
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DOI: 10.1021/acsabm.2c00496
Magnetically responsive composite polymer scaffolds have good potential for a variety of biomedical applications. In this work, electrospun composite scaffolds made of polyhydroxybutyrate (PHB) and magnetite (Fe3O4) particles (MPs) were studied before and after degradation in either PBS or a lipase solution. MPs of different sizes with high saturation magnetization were synthesized by the coprecipitation method followed by coating with citric acid (CA). Nanosized MPs were prone to magnetite–maghemite phase transformation during scaffold fabrication, as revealed by Raman spectroscopy; however, for CA-functionalized nanoparticles, the main phase was found to be magnetite, with some traces of maghemite. Submicron MPs were resistant to the magnetite–maghemite phase transformation. MPs did not significantly affect the morphology and diameter of PHB fibers. The scaffolds containing CA-coated MPs lost 0.3 or 0.2% of mass in the lipase solution and PBS, respectively, whereas scaffolds doped with unmodified MPs showed no mass changes after 1 month of incubation in either medium. In all electrospun scaffolds, no alterations of the fiber morphology were observed. Possible mechanisms of the crystalline-lamellar-structure changes in hybrid PHB/Fe3O4 scaffolds during hydrolytic and enzymatic degradation are proposed. It was revealed that particle size and particle surface functionalization affect the mechanical properties of the hybrid scaffolds. The addition of unmodified MPs increased scaffolds’ ultimate strength but reduced elongation at break after the biodegradation, whereas simultaneous increases in both parameters were observed for composite scaffolds doped with CA-coated MPs. The highest saturation magnetization─higher than that published in the literature─was registered for composite PHB scaffolds doped with submicron MPs. All PHB scaffolds proved to be biocompatible, and the ones doped with nanosized MPs yielded faster proliferation of rat mesenchymal stem cells. In addition, all electrospun scaffolds were able to support angiogenesis in vivo at 30 days after implantation in Wistar rats.
[98]
Honeycomb-structured porous films from poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate): physicochemical characterization and mesenchymal stem cells behavior
Kulikouskaya V.I., Nikalaichuk V.V., Bonartsev A.P., Akoulina E.A., Belishev N.V., Demianova I.V., Chesnokova D.V., Makhina T.K., Bonartseva G.A., Shaitan K.V., Hileuskaya K.K., Voinova V.V.
Polymers.
2022,
vol. 14, № 2671, 1–23.
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DOI: 10.3390/polym14132671
Surface morphology affects cell attachment and proliferation. In this research, different films made of biodegradable polymers, poly(3-hydroxybutyrate) (PHB) and poly(3-hydroxybutyrateco-3-hydroxyvalerate) (PHB-co-HV), containing different molecular weights, with microstructured surfaces were investigated. Two methods were used to obtain patterned films—water-assisted self-assembly (“breath figure”) and spin-coating techniques. The water-assisted technique made it possible to obtain porous films with a self-assembled pore structure, which is dependent on the monomer composition of a polymer along with its molecular weight and the technique parameters (distance from the nozzle, volume, and polymer concentration in working solution). Their pore morphologies were evaluated and their hydrophobicity was examined. Mesenchymal stem cells (MSCs) isolated from bone marrow were cultivated on a porous film surface. MSCs’ attachment differed markedly depending on surface morphology. On strip-formed stamp films, MSCs elongated along the structure, however, they interacted with a larger area of film surface. The honeycomb films and column type films did not set the direction of extrusion, but cell flattening depended on structure topography. Thus, stem cells can “feel” the various surface morphologies of self-assembled honeycomb films and change their behavior depending on it.
[97]
Competitive Biosynthesis of Bacterial Alginate Using Azotobacter vinelandii 12 for Tissue Engineering Applications
Dudun A.A., Akoulina E.A., Zhuikov V.A., Makhina T.K., Voinova V.V., Belishev N.V., Khaydapova D.D., Shaitan K.V., Bonartseva G.A., Bonartsev A.P.
Polymers.
2022,
vol. 14, № 131, 1–21.
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DOI: 10.3390/polym14010131
This study investigated the effect of various cultivation conditions (sucrose/phosphate concentrations, aeration level) on alginate biosynthesis using the bacterial producing strain Azotobacter vinelandii 12 by the full factorial design (FFD) method and physicochemical properties (e.g., rheological properties) of the produced bacterial alginate. We demonstrated experimentally the applicability of bacterial alginate for tissue engineering (the cytotoxicity testing using mesenchymal stem cells (MSCs)). The isolated synthesis of high molecular weight (Mw) capsular alginate with a high level of acetylation (25%) was achieved by FFD method under a low sucrose concentration, an increased phosphate concentration, and a high aeration level. Testing the viscoelastic properties and cytotoxicity showed that bacterial alginate with a maximal Mw (574 kDa) formed the densest hydrogels (which demonstrated relatively low cytotoxicity for MSCs in contrast to bacterial alginate with low Mw). The obtained data have shown promising prospects in controlled biosynthesis of bacterial alginate with different physicochemical characteristics for various biomedical applications including tissue engineering.
[96]
Models of Head and Neck Squamous Cell Carcinoma Using Bioengineering Approaches
Bonartsev A.P., Lei Bo, Kholina M.S., Menshikh K.A., Svyatoslavov D.S., Samoylova S.I., Sinelnikov M.Y., Voinova V.V., Shaitan K.V., Kirpichnikov M.P., Reshetov I.V.
Critical Reviews in Oncology/Hematology.
2022,
vol. 175, № 103724, 1–15.
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DOI: 10.1016/j.critrevonc.2022.103724
The use of bioengineering methods and approaches is extremely promising for the development of experimental models of cancer, especially head and neck squamous cell carcinomas (HNSCC) that are characterized by early metastasis and rapid progression., for testing novel anticancer drugs and diagnostics. This review summarizes the most relevant HNSCC tumor models used to this day as well as future directions for improved modeling of the malignant disease. Apart from conventional 2D-cell cultivation methods and in vivo animal cancer models a number of bioengineering techniques of modeling HNSCC tumors were reported: genetic-engineering, ethanol/tobacco exposure experiment, spheroids, hydrogel-based cell culture, scaffold-based cell culture, microfluidics, bone-tumor niche cell culture, cancer and normal cells co-culture, cancer cells, and bacteria co-culture. An organized set of these models can constitute a system of HNSCC experimental modeling, which gives potential towards developing the newest approaches in the diagnosis, prevention, and treatment of HNSCC.
[95]
Cryo-Structuring of Polymeric Systems. Poly(vinyl alcohol)-based cryogels loaded with the poly(3-hydroxybutyrate) microbeads and the evaluation of such composites as the delivery vehicles for simvastatin
Michurov D.A., Makhina T.K., Siracusa V., Bonartsev A.P., Lozinsky V.I., Iordanskii A.L.
Polymers.
2022,
vol. 14, № 2196, 1–15.
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DOI: 10.3390/polym14112196
Highly porous composite poly(vinyl alcohol) (PVA) cryogels loaded with the poly(3-hydroxybutyrate) (PHB) microbeads containing the drug, simvastatin (SVN), were prepared via cryogenic processing (freezing—storing frozen—defrosting) of the beads’ suspensions in aqueous PVA solution. The rigidity of the resultant composite cryogels increased with increasing the filler content. Optical microscopy of the thin section of such gel matrices revealed macro-porous morphology of both continuous (PVA cryogels) and discrete (PHB-microbeads) phases. Kinetic studies of the SVN release from the drug-loaded microbeads, the non-filled PVA cryogel and the composite material showed that the cryogel-based composite system could potentially serve as a candidate for the long-term therapeutic system for controlled drug delivery. Such PHB-microbeads-containing PVA-cryogel-based composite drug delivery carriers were unknown earlier; their preparation and studies have been performed for the first time.
[94]
Biocompatibility and Bioresorption of 3D-Printed Polylactide and Polyglycolide Tissue Membranes
Kim E.V., Petronyuk Y.S., Guseynov N.A., Tereshchuk S.V., Popov A.A., Volkov A.V., Gorshenev V.N., Olkhov A.A., Levin V.M., Dymnikov A.B., Rodionov V.E., Tumanyan G.A., Ivashkevich S.G., Bonartsev A.P., Borozdkin L.L.
Bulletin of Experimental Biology and Medicine.
2021,
vol. 170, № 3, 356–359.
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DOI: 10.1007/s10517-021-05066-x
We studied biocompatibility and bioresorption of 3D-printed polylactide and polyglycolide tissue membranes. Ultrasound microscopy and histological examination showed that membranes fabricated of a copolymer of lactic and glycolic acids in a mass ratio of 1:9 are bioresorbed and have good biocompatibility with soft tissues (connective tissue, adipose tissue, and epithelium). An important feature of the copolymer membranes, which differs them from pure polylactide membranes, is the formation of a thin fibrous capsule that did not interfere its destruction by the mechanism of hydrolytic resorption.
[93]
Internet of Things and Robotics in Transforming Current-Day Healthcare Services
Pradhan B., Bharti D., Chakravarty S., Ray S.S., Voinova V.V., Bonartsev A.P., Pal K.
Journal of healthcare engineering.
2021,
vol. 2021, 1–15.
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DOI: 10.1155/2021/9999504
Technology has become an integral part of everyday lives. Recent years have witnessed advancement in technology with a wide range of applications in healthcare. However, the use of the Internet of Things (IoT) and robotics are yet to see substantial growth in terms of its acceptability in healthcare applications. The current study has discussed the role of the aforesaid technology in transforming healthcare services. The study also presented various functionalities of the ideal IoT-aided robotic systems and their importance in healthcare applications. Furthermore, the study focused on the application of the IoT and robotics in providing healthcare services such as rehabilitation, assistive surgery, elderly care, and prosthetics. Recent developments, current status, limitations, and challenges in the aforesaid area have been presented in detail. The study also discusses the role and applications of the aforementioned technology in managing the current pandemic of COVID-19. A comprehensive knowledge has been provided on the prospect of the functionality, application, challenges, and future scope of the IoT-aided robotic system in healthcare services. This will help the future researcher to make an inclusive idea on the use of the said technology in improving the healthcare services in the future.
[92]
The Growth of 3T3 Fibroblasts on PHB, PLA and PHB/PLA Blend Films at Different Stages of Their Biodegradation In Vitro
Zhuikov V.A., Akoulina E.A., Chesnokova D.V., Wenhao Y., Makhina T.K., Demyanova I.V., Zhuikova Y.V., Voinova V.V., Belishev N.V., Surmenev R.A., Surmeneva M.A., Bonartseva G.A., Shaitan K.V., Bonartsev A.P.
Polymers.
2021,
vol. 12, № 1, 108–131.
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DOI: 10.3390/polym13010108
Over the past century there was a significant development and extensive application of biodegradable and biocompatible polymers for their biomedical applications. This research investigates the dynamic change in properties of biodegradable polymers: poly(3-hydroxybutyrate (PHB), poly-L-lactide (PLA), and their 50:50 blend (PHB/PLA)) during their hydrolytic non-enzymatic (in phosphate buffered saline (PBS), at pH = 7.4, 37°C) and enzymatic degradation (in PBS supplemented with 0.25 mg/mL pancreatic lipase). 3T3 fibroblast proliferation on the polymer films experiencing different degradation durations was also studied. Enzymatic degradation significantly accelerated the degradation rate of polymers compared to non-enzymatic hydrolytic degradation, whereas the seeding of 3T3 cells on the polymer films accelerated only the PLA molecular weight loss. Surprisingly, the immiscible nature of PHB/PLA blend (showed by differential scanning calorimetry) led to a slower and more uniform enzymatic degradation in comparison with pure polymers, PHB and PLA, which displayed a two-stage degradation process. PHB/PLA blend also displayed relatively stable cell viability on films upon exposure to degradation of different durations, which was associated with the uneven distribution of cells on polymer films. Thus, the obtained data are of great benefit for designing biodegradable scaffolds based on polymer blends for tissue engineering.
[91]
Противовоспалительное и остеоиндуктивное действие симвастатина, возможности его использования для лечения заболеваний пародонта
Ивашкевич С.Г., Асфаров Т.Ф., Бонарцев А.П., Гусейнов Н.А., Хоссаин Ш.Д.
Клиническая стоматология.
2021,
№ 1, 66–74.
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DOI: 10.37988/1811-153x_2021_1_66
Реферат. Успешное применение хирургических и медикаментозных методов лечения восстановления костной ткани челюстей убедительно подтверждено в клинической практике. Вместе с тем продолжают развиваться технологии по потенцированию остеоиндуктивных свойств остеопластических материалов для восстановления костного объема. Включение в состав остеопластических материалов статинов самостоятельно или в комбинации с МСК — одно из новых и многообещающих направлений регенераторного воздействия.
Цель обзора — сбор и анализ научных данных о влиянии симвастатина на дифференцировку МСК, участие симвастатина при воспалительных процессах в тканях пародонта, поиск перспектив применения симвастатина как составляющей комплексной терапии заболеваний пародонта.
Материалы и методы. Поиск данных проводили на основе баз данных pubmed.com, sciencedirect.com, elibrary.ru по ключевым словам: «simvastatin» AND «periodontitis», «simvastatin» AND «stromal mesenchymal cells» с 2014 г. до 2020 г. Были отобраны статьи на основе экспериментальных работ.
Результаты.Подчеркнуты основные клеточно-генетические пути реализации работы симвастатина по отношению к МСК и заболеваниям пародонта, выявлена корреляционная связь дозозависимого применения симвастатина с дифференцировкой МСК и выраженностью воспалительного ответа при заболеваниях пародонта.
Заключение. Симвастатин является перспективным средством при заболеваниях пародонта как на воспалительном, так и на реабилитационном этапах.
[90']
Growth of Mesenchymal Stem Cells on Poly(3-Hydroxybutyrate) Scaffolds Loaded with Simvastatin
Akoulina E.A., Demianova I.V., Zharkova I.I., Voinova V.V., Zhuikov V.A., Khaydapova D.D., Chesnokova D.V., Menshikh K.A., Dudun A.A., Makhina T.K., Bonartseva G.A., Volkov A.V., Asfarov T.F., Ivanov S.Y., Shaitan K.V., Bonartsev A.P.
Bulletin of Experimental Biology and Medicine.
2021,
vol. 171, № 1, 172–177.
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DOI: 10.1007/s10517-021-05190-8
We studied the effect of porous composite scaffolds based on poly(3-hydroxybutyrate) (PHB) loaded with simvastatin on the growth and differentiation of mesenchymal stem cells. The scaffolds have a suitable microstructure (porosity and pore size) and physicochemical properties to support the growth of mesenchymal stem cells. Scaffold loading with simvastatin suppressed cell growth and increased alkaline phosphatase activity, which can attest to their osteoinductive properties.
[90]
Рост мезенхимных стволовых клеток на матриксах на основе поли-3-оксибутирата, загруженных симвастатином
Акулина Е.А., Демьянова И.В., Жаркова И.И., Воинова В.В., Жуйков В.А., Хайдапова Д.Д., Чеснокова Д.В., Меньших К.А., Дудун А.А., Махина Т.К., Бонарцева Г.А., Волков А.В., Асфаров Т.Ф., Иванов С.Ю., Шайтан К.В., Бонарцев А.П.
Клеточные технологии в биологии и медицине.
2021,
№ 1, 70–76.
Абстракт
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DOI: 10.47056/1814-3490-2021-1-70-76
В данной работе исследовано влияние пористых композитных матриксов на основе поли-3-оксибутирата (ПОБ), загруженных симвастатином, на рост и дифференцировку мезенхимальных стволовых клеток (МСК). Показано, что полученные матриксы обладают подходящей микроструктурой (пористость и размер пор) и физико-химическими свойствами для поддержания роста МСК. Матриксы, загруженные симвастатином, вызывали угнетение роста клеток и возрастание активности щелочной фосфатазы, что может указывать на их остеоиндуктивные свойства.
[89]
Экспериментальные модели роста опухолевых клеток на полимерных микросферах и сокультивирования с мезенхимальными стволовыми клетками
Самойлова С.И., Святославов Д.С., Решетов И.В., Бонарцев А.П., Холина М.С., Жаркова И.И., Воинова В.В., Шайтан К.В.
Head and Neck/Голова и шея.
2021,
том 2, № 9, 85–86.
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DOI: 10.25792/HN.2021.9.2
Для исследования противоопухолевых препаратов в качестве переходного звена между моделями для скрининга новых лекарств и средств ранней диагностики in vitro и тестированием препаратов на животных моделях опухолевых заболеваний in vivo разрабатывают биоинженерные модели трёхмерного роста опухолевых клеток. Особенно актуально создание таких модельных систем для моделирования in vitro плоскоклеточного рака головы и шеи (ПРГШ).
[88]
Matrices for Tissue Engineering Based on Ultrafine Fibers and Microparticles of Poly(hydroxybutyrate)
Bonartsev A.P., Ol’khov A.A., Khan O.I., Kucherenko E.L., Filatova A.G., Zernova Yu N., Iordanskii A.L.
Inorganic Materials: Applied Research.
2021,
vol. 12, 974–979.
Абстракт
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DOI: 10.1134/S2075113321040080
The structure and diffusion properties of combined ultrafibrous matrices containing microspheres for prolonged release of lysozyme are studied in the work. The matrices are biocompatible and they are not cytotoxic. The matrices are obtained via electrospinning. These materials are suitable for solving problems of tissue engineering, since they combine ultrafine fibers of poly(hydroxybutyrate) promoting effective attachment and growth of cells and poly(hydroxybutyrate) microparticles capable of prolonged release of a bioactive compound. These properties allow one to recommend these matrices for tissue engineering.
[87]
Comparative structure-property characterization of poly(3-hydroxybutyrate-co-3-hydroxyvalerate)s films under hydrolytic and enzymatic degradation: finding a transition point in 3-hydroxyvalerate content
Zhuikov V.A., Zhuikova Y.V., Makhina T.K., Myshkina V.L., Rusakov A., Useinov A., Voinova V.V., Bonartseva G.A., Berlin A.A., Bonartsev A.P., Iordanskii A.L.
Polymers.
2020,
vol. 12, № 728, 1–15.
Абстракт
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DOI: 10.3390/polym12030728
The hydrolytic and enzymatic degradation of polymer films of poly(3-hydroxybutyrate)(PHB) of different molecular mass and its copolymers with 3-hydroxyvalerate (PHBV) of different 3-hydroxyvalerate (3-HV) content and molecular mass, 3-hydroxy-4-methylvalerate (PHB4MV), and polyethylene glycol (PHBV-PEG) produced by the Azotobacter chroococcum 7B by controlled biosynthesis technique were studied under in vitro model conditions. The changes in the physicochemical properties of the polymers during their in vitro degradation in the pancreatic lipase solution and in phosphate-buffered saline for a long time (183 days) were investigated using different analytical techniques. A mathematical model was used to analyze the kinetics of hydrolytic degradation of poly(3-hydroxyaklannoate)s by not autocatalytic and autocatalytic hydrolysis mechanisms. It was also shown that the degree of crystallinity of some polymers changes differently during degradation in vitro. The total mass of the films decreased slightly up to 8–9% (for the high-molecular weight PHBV with the 3-HV content 17.6% and 9%), in contrast to the copolymer molecular mass, the decrease of which reached 80%. The contact angle for all copolymers after the enzymatic degradation decreased by an average value of 23% compared to 17% after the hydrolytic degradation. Young’s modulus increased up to 2-fold. It was shown that the effect of autocatalysis was observed during enzymatic degradation, while autocatalysis was not available during hydrolytic degradation. During hydrolytic and enzymatic degradation in vitro, it was found that PHBV, containing 5.7–5.9 mol.% 3-HV and having about 50% crystallinity degree, presents critical content, beyond which the structural and mechanical properties of the copolymer have essentially changed. The obtained results could be applicable to biomedical polymer systems and food packaging materials.
[86]
Poly(3-hydroxybutyrate)/hydroxyapatite/alginate scaffolds seeded with mesenchymal stem cells enhance the regeneration of critical-sized bone defect
Volkov A.V., Muraev A.A., Zharkova I.I., Voinova V.V., Akoulina E.A., Zhuikov V.A., Khaydapova D.D., Chesnokova D.V., Menshikh K.A., Dudun A.A., Makhina T.K., Bonartseva G.A., Asfarov T.F., Stamboliev I.A., Gazhva Y.V., Ryabova V.M., Zlatev L.H., Ivanov S.Y., Shaitan K.V., Bonartsev A.P.
Materials Science and Engineering C.
2020,
vol. 114, 1–14.
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DOI: 10.1016/j.msec.2020.110991
A critical-sized calvarial defect in rats is employed to reveal the osteoinductive properties of biomaterials. In this study, we investigate the osteogenic efficiency of hybrid scaffolds based on composites of a biodegradable and biocompatible polymer, poly(3-hydroxybutyrate) (PHB) with hydroxyapatite (HA) filled with alginate (ALG) hydrogel containing mesenchymal stem cells (MSCs) on the regeneration of the critical-sized radial defect of the parietal bone in rats. The scaffolds based on PHB and PHB/HA with desired shapes were prepared by two-stage salt leaching technique using a mold obtained by three-dimensional printing. To obtain PHB/HA/ALG/MSC scaffolds seeded with MSCs, the scaffolds were filled with ALG hydrogel containing MSCs; acellular PHB/ALG and PHB/ALG filled with empty ALG hydrogel were prepared for comparison. The produced scaffolds have high porosity and irregular interconnected pore structure. PHB/HA scaffolds supported MSC growth and induced cell osteogenic differentiation in a regular medium in vitro that was manifested by an increase in ALP activity and expression of the CD45 phenotype marker. The data of computed tomography and histological studies showed 94% and 92%, respectively, regeneration of critical-sized calvarial bone defect in vivo at 28th day after implantation of MSC-seeded PHB/HA/ALG/MSC scaffolds with 3.6 times higher formation of the main amount of bone tissue at 22–28 days in comparison with acellular PHB/HA/ALG scaffolds that was shown at the first time by fluorescent microscopy using the original technique of intraperitoneal administration of fluorescent dyes to living postoperative rats. The obtained in vivo results can be associated with the MSC-friendly microstructure and in vitro osteogenic properties of PHB/HA base-scaffolds. Thus, the obtained data demonstrate the potential of MSCs encapsulated in the bioactive biopolymer/mineral/hydrogel scaffold to improve the bone regeneration process in critical-sized bone defects.
[85]
Growth of mesenchymal stem cells on poly(3-hydroxybutyrate) scaffolds loaded with simvastatin
Akoulina E.A., Demianova I.V., Zharkova I.I., Voinova V.V., Zhuikov V.A., Khaydapova D.D., Chesnokova D.V., Menshikh K.A., Dudun A.A., Makhina T.K., Bonartseva G.A., Volkov A.V., Asfarov T.F., Ivanov S.Y., Shaitan K.V., Bonartsev A.P.
Bull Exp Biol Med.
2020,
vol. 171, 172–177.
Абстракт
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DOI: 10.1007/s10517-021-05190-8
We studied the efect of porous composite scafolds based on poly(3-hydroxybutyrate) (PHB) loaded with simvastatin on the growth and diferentiation of mesenchymal stem cells. The scafolds have a suitable microstructure (porosity and pore size) and physicochemical properties to support the growth of mesenchymal stem cells. Scafold loading with simvastatin suppressed cell growth and increased alkaline phosphatase activity, which can attest to their osteoinductive properties.
[84]
Рост мезенхимальных стволовых клеток на плёнках поли-3-оксибутирата, загруженных левофлоксацином и симвастатином
Демьянова И.В., Акулина Е.А., Труонг T.Х., Воинова В.В., Махина Т.К., Бонарцева Г.А., Бонарцев А.П.
Биологический Журнал.
2020,
том. 15, № 4, 4–9.
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DOI: 10.32743/2658-6460.2020.4.15.283
Были получены пленки из биоразлагаемого и биосовместимого полимера поли-3-оксибутирата, загруженные антибиотиком левофлоксацином (1% и 5% вес.) и остеоиндуктором симвастатином (1% и 5% вес.). Исследование пролиферации мезенхимальных стволовых клеток на поверхности полученных пленок показало, что пленки из поли-3-оксибутирата, загруженные левофлоксацином (1% и 5%) и симвастатином (1%) способствуют поддержанию жизнеспособности и пролиферации мезенхимальных стволовых клеток на поверхности пленки, но на пленках, содержащих 5% симвастатина рост наблюдалось подавление роста клеток. Лекарственные системы на основе ПОБ обладают хорошими перспективами для применения с целью регенерации костной ткани.
[83]
Биосовместимость и скорость резорбции тканевых мембран из полилактида и полигликолида, изготовленных методом 3D-печати
Ким Э.В., Петронюк Ю.С., Гусейнов Н.А., Терещук С.В., Попов А.А., Волков А.В., Горшенев В.Н., Ольхов А.А., Левин В.М., Дымников А.Б., Родионов В.Э., Туманян Г.А., Ивашкевич С.Г., Бонарцев А.П., Бороздкин Л.Л.
Бюллетень экспериментальной биологии и медицины.
2020,
том. 170, № 9, 352–356.
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DOI: 10.47056/0365-9615-2020-170-9-352-356
Проведено исследование биосовместимости и скорости резорбции тканевых мембран из полилактида и полигликолида, изготовленных методом 3D-печати. Результаты ультразвуковой микроскопии и гистологического исследования продемонстрировали, что мембраны из сополимера молочной и гликолевой кислот в массовом соотношении 1:9 подвергаются биорезорбции и имеют хорошую биосовместимость с мягкими тканями (соединительная ткань, жировая клетчатка и эпителий). Важным отличием от чистого полилактида является образование вокруг мембран из сополимера фиброзной капсулы незначительной толщины, которая не препятствует деструкции, протекающей по механизму гидролитической резорбции.
[82']
Developing Techniques of Acoustic Microscopy for Monitoring Processes of Osteogenesis in Regenerative Medicine
Petronyuk Yu S., Khramtsova E.A., Levin V.M., Bonartsev A.P., Voinova V.I., Bonartseva G.A., Muraev A.A., Asfarov T.F., Guseynov N.A.
Bulletin of the Russian Academy of Sciences: Physics.
2020,
vol. 84, № 6, 653–565.
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DOI: 10.3103/s1062873820060179
High-resolution ultrasonic imaging techniques are necessary for the non-invasive diagnostics of artificial cell-matrix systems. The results from experimental studies show these techniques are sensitive to variations in the elastic properties of biopolymer samples and can be used effectively to detect micro and macro voids and monitor processes of biodegradation in tissue-engineered constructs (TECs).
[82]
Развитие методов акустической микроскопии для наблюдения процессов остеогенеза в регенеративной медицине
Петронюк Ю.С., Храмцова Е.А., Левин В.М., Бонарцев А.П., Воинова В.В., Бонарцева Г.А., Мураев А.А., Асфаров Т.Ф., Гусейнов Н.А.
Известия Российской академии наук. Серия физическая.
2020,
том. 86, № 6, 799–802.
Абстракт
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DOI: 10.31857/S0367676520060204
Ультразвуковые методы визуализации высокого разрешения необходимы для неинвазивной диагностики искусственных клеточно-матричных систем. Результаты экспериментальных исследований показывают, что метод чувствителен к вариациям упругих свойств биополимерных образцов, эффективен для обнаружения микро- и макропустот и наблюдения за процессами биодеградации в тканеинженерных конструкциях (ТИК).
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