Composite materials with dacarbazine (DK) containing 1 wt. % were obtained on the basis of polyurethane ureas (PUU) containing in the structure as extenders of the macrochain of 2-(2-aminoethoxy)ethan-1-amine, (DA1) 3,6-dioxaoctane-1,8-diamine (DA2) 3-{2-[2-(3-aminopropoxy)ethoxy]ethoxy}propan-1-amine (DA3) with a molar ratio of 4,4’-diaminodiphenylmethane (DADPh) to DA1 and DA3 as 30:70; 50:50; 70:30. The tensile strength of the compositions is within (1.21-1.27) MPa, the relative elongation is (303.9-384)%. Studies of thermophysical properties of synthesized PUU by DSC, TGA methods were conducted. Dacarbazine compositions are single-phase systems with glass transition temperature (Tg) from -33.55°C to -37.06°C. It was established that the introduction of Dacarbazine into the composition of PUU leads to a decrease in Tg and ΔCp during the second warm-up in comparison with the original PUU. Dacarbazine compositions are resistant to temperatures of 270oC, which allows for thermal sterilization before use. The release of Dacarbazine from polymer samples into the solution was studied by the spectrophotometric method. According to the results of the study of the dynamics release of Dacarbazine, it was es tablished that for (PUU DA1)2+DK in 14 days it is 61.74%, (PUU DA2)4+DK - 70.09%, (PUU DA3)2+DK - 56.75% of the total amount of immobilized DK. The resulting composites are perspective materials for medicine as means of local prolonged therapeutic action.

The problem of scientific investigations in the selection of fixators for osteosynthesis in treating ailments with fractures and deformities of the facial skeleton bones, which will require reconstructive surgery, is considered. Literature data on the use of various types of materials for osteosynthesis are given. It was established that the development of new biologically active composite materials for the production of bone plates for osteosynthesis, which would meet the basic requirements of bone surgery: biocompatibility, strength, flexibility, ability to biodegrade, stimulation of tissue regeneration and prolonged therapeutic action, is an urgent direction of modern science and practical medicine. To solve this problem, the use of fixation structures for osteosynthesis based on biodegraded epoxy polyurethane (EPU) composite material with bioactive action (EPU-HAP-LEV) is proposed. Biological activity is ensured by the presence of hydroxyapatite and levamisole fillers in the EPU composite. Representative results of physical-mechanical, physical-chemical, and medical-biological studies, which preceded clinical trials of the composite material EPU–HAP–LEV in the form of osseous plates for osteosynthesis, are given. According to the obtained results, the EPU–HAP–LEV composite material is non-toxic, biocompatible and bioactive, capable of biodegradation and prolonged release of levamisole, has the necessary strength characteristics (flexural strength - 27.1 MPa, tensile strength - 24 MPa, relative elongation at break 5.3 MPa), which made it possible to manufacture fixators for osteosynthesis in the maxillofacial area and allowed to recommend them for clinical use. In the clinic, 76 patients with facial skull fractures were treated with polymer plates with screws, which are made of the EPU-HAP-LEV composition. An example of the clinical use of bone plates for osteosynthesis made of EPU-LEV-HAP is presented and their compliance with the medical purpose, effectiveness in the surgical treatment of maxillofacial fractures in areas that do not bear a significant masticatory load, as well as in biomechanically stable fractures is established.

Background: Restorative orbital and periorbital surgeries require implantable materials containing antimicrobial and anticancer medications. Purpose: To assess rat tissue responses to dacarbazine-containing implants made of cross-linked polyurethane of different densities. Material and Methods: Dacarbazine (DC)-containing polyurethane-urea foam (PUUF) implants were a subject of research. We studied the dynamics of DC release from these implant samples. Soft tissue cellular responses to the developed composites were assessed through the implantation of the latter in Wistar rats. Results: We found that the number of open pores impacts implant survival. There was no substantial difference in DC release between the PUUF samples with a DC weight percent of 1% and those with a DC weight percent of 0.5% at incubation days 1 to 3. At days 5, 7 and 14, an increase in DC release was higher in the former samples than in the latter samples (64% versus 55%). In animals with a subcutaneously implanted PUUF sample, there was histological evidence of (a) formation of a capsule and tight network of blood vessels surrounding an implanted sample at day 3, and (b) separation of the implanted material from the surrounding tissues by a wide cuff of lymphocytes and a thick connective tissue capsule (CTC) at day 7. Conclusion: The number of open pores impacts DC release and the speed of connective tissue ingrowth into the porous matrix. It was found that a CTC formed around all implants at early time points and at day 30, which in combination with the presence of DC in composite materials resulted in long-term cellular inflammation at the implant placement site.

Мета роботи: покращити результати лікування пацієнтів із пілонідальними кістами крижово-куприкової ділянки шляхом комплексного хірургічного лікування з використанням клею на основі сітчастого поліуретану. Матеріали і методи. Проведено аналіз хірургічного лікування 126 пацієнтів з пілонідальною кістою крижово-куприкової ділянки. Вік пацієнтів від був 18 до 46 років, середній вік пацієнтів склав 27±1,2 року. Чоловіків було 111 (88 %), жінок 15 (12 %). Залежно від способу лікування пацієнти були розподілені на 2 групи. Групи пацієнтів були зіставні за віковим та статтю (p>0,05). У першій групі (64 пацієнти) хірургічне лікування проводили за розробленим нами способом економної резекції з накладанням двох рядів внутрішніх позаепідермальних швів у поєднанні з клейовою композицією на основі сітчастого поліуретану з іммобілізованим альбуцидом. У другій групі (62 пацієнти) хірургічне лікування пілонідальних кіст виконувалось за традиційним способом серединної резекції з використанням вузлових швів нашкірної фіксації. Жоден з пацієнтів раніше не був оперований з приводу пілонідальної кісти. Хірургічне лікування здійснювали під місцевим знеболенням. Всіх пацієнтів було прооперовано амбулаторно. Час післяопераційного спостереження пацієнтів складав 12–24 місяців. Результати досліджень та їх обговорення. У післяопераційному періоді серед пацієнтів 64 пацієнтів 1-ї групи у 4 (6,3 %) пацієнтів спостерігали серому п/о рани, інфікування рани у 1 (1,6 %) пацієнта, гематом рани не спостерігали, рецидив пілонідальної кісти було діагностовано у 1 (1,6 %) пацієнта з ожирінням ІІІ ступеня, цукровим діабетом. Серед 62 пацієнтів 2-ї групи у 16 (25,8 %) пацієнтів спостерігали виникнення сероми п/о рани. Інфікування післяопераційної рани спостерігали у 10 (16,1 %) пацієнтів. Наявність гематоми спостерігали у 2 (3,2 %) пацієнтів. Рецидив захворювання спостерігали у 6 (9,7 %) пацієнтів, у термін від 1 до 3 місяців. За даними результатів, значне покращення хірургічного лікування пілонідальних кіст досягнуто у пацієнтів 1-ї групи, які були прооперовані за розробленою методикою з використанням клейової композиції.

The study of biodegradation ability of polyurethane foams composite materials with lysozyme under the influence of saline solution for 2 weeks, 1, 3 and 6 months by IR spectroscopy, DSC, TGA was conducted. According to the results of IR spectroscopy under the influence of model medium there are processes of biodegradation, which are confirmed by a decrease in the intensity of the absorption band νС=О. Along with biodegradation there is a redistribution of hydrogen bonds of NH and CO groups of polymer matrix. According to DSC after incubation in saline solution there is an increase in Tg and ΔCp at the glass-transition (for polyurethane foams and composites with lysozyme in the amount of 5 wt. %), an increase in Tg and decrease in ΔCp (for composites with lysozyme in the amount of 1 and 3 wt. %), which indicates the redistribution of hydrogen bonds under the influence of saline solution and due to lysozyme release. It was found that after incubation in saline solution there is an increase in T0 and Tmax for both polyurethane foams and composite materials with lysozyme by the method of TGA. Thus, composites with lysozyme in vitro are heat-resistant materials. According to the study results of the dynamics of lysozyme release composites are capable to the prolonged release of enzyme for 5 days, the amount of which varies depending on the lysozyme content (43.85-61.97 % of the total amount of the introduced drug) and is sufficient for the manifestation of antimicrobial activity. The tissue culture method has established the biocompatibility of investigated materials. For polyurethane foam composite materials with lysozyme more active growth of fibroblastic elements than in the control and polyurethane foam and slowing down the process of cell degeneration was observed. The obtained results indicate that polyurethane foam composite materials with lysozyme are promising materials that due to the presence of the enzyme will have antimicrobial action and can be used in medical practice as polymer composites for the treatment of wounds and burns.

Modern medicine needs new polymer materials for the manufacture of catheters, drains and a variety of film coatings with resistant antimicrobial properties that will ensure suppression of infection in the product and the focus of inflammation. Since the main requirements for medical polymer materials are biocompatibility and non-toxicity there is a need for preclinical tests. The aim of the work is to study the cytotoxicity and biocompatibility of composite materials filled with silver-containing silica nanocomposite 02AgCu. Object and methods of research. The objects of the study were composite materials based on polyurethaneureas (PUU) with copolymer fragments of poly(vinyl butyral-vinyl acetate-vinyl alcohol) and macrochain extender 1,6-hexamethylenediamine in the structure filled with silver-containing silica nanocomposite 02AgCu in the amount of 1 wt. %. Cytotoxicity studies were performed by tissue culture method on the culture of tissue of subcutaneous fatty tissue of white laboratory rats in vitro. Biocompatibility studies were performed by histological tests by studying cellular responses to the implantation of polymer materials in vivo. Results. According to the results of tissue culture studies it can be concluded that there is no histotoxic effect of the investigated PUU and composite materials on their basis filled with silver-containing silica nanocomposite on cultured cells. Histological tests showed that the polymer samples had a fairly high degree of biocompatibility. Conclusions. The investigated composite materials filled with silver-containing silica nanocomposite 02AgCu in the amount of 1 wt. % are safe and can be proposed for use in various branches of medicine.

Developed a new composite material with Dacarbazine based on polyurethane foam (PPUS) The content of the drug substance Dacarbazine (DAC) in the composition was 0.5 wt. % and 1.0 wt.%. PPUS was obtained on the basis of a mixture of oligourethane diisocyanates (OUDIC) synthesized on the basis of 2,4-;2,6-toluene diisocyanate and polyoxypropylene glycols (POPG) MM 1002 and MM 2002 in a ratio of 1:1. Comparative physical and mechanical tests were performed. According to the obtained results, PPUS with DAC in the amount of 1 wt.% have physical and mechanical parameters (σ = 7.8, MPa, ε = 100% and σadhesion = 4.5 MPa), that will meet the requirements for replacement implants for ophthalmology. According to the results of IR spectroscopy, the possibility of chemical immobilization of Dacarbazine on the selected polymeric carrier was established. The thermophysical properties of the synthesized PPUS with Dacarbazine by DSC and TGA methods were studied. It was found that the glass transition temperature (Tg) is practically independent of the content of DAC. Tg PPUS with 0.5 wt.% DAC - (minus) 49.70 °C, Tg PPUS with 1.0 wt.% DAC - (minus) 50.09 °C. According to TGA, the obtained materials are characterized by the same heat resistance characteristics and practically do not depend on the content of DAC. The onset temperature of thermal decomposition (To) is in the range (290,96–298,61) °C and is accompanied by a slight weight loss (0.02–0.04 %). The temperature of maximum decomposition rate (Tmax ) is in the range (331.93–333.95) °C. According to the results of the dynamics of Dacarbazine release study from PPUS samples with a DAC content in the composition of 0.5 and 1.0 wt. % found that the composition of PPUS with a content of DAC 1 wt. % have a higher percentage of medicine, which on day 14 is ~ 64 %. The developed PPUS with Dacarbazine are promising materials for use as implants for ophthalmological surgery.

A series of polymeric composites based on polyurethanes with copolymer fragments of poly(vinyl butyral-vinyl acetate-vinyl alcohol) and 1,6-hexamethylenediamine filled with modified precipitated silica were synthesized. The content of silver in the nanocomposites was 0.1–0.2 and of copper – 0.14 and 0.2 mmol per 1 g of SiO2 (02AgCu; AgCu and 01Ag samples). The content of silver-containing silica filler in the polymer composites was 0.1, 0.5 and 1.0 wt. %. By means of the IR spectroscopy, it has been found that a physical immobilization of modified silica in the polymeric matrix takes place due to the presence of intermolecular hydrogen bonds. The influence of fillers on the structure and properties of polymer materials, in particular, on thermophysical properties and physico-mechanical parameters (tensile strength and relative elongation at rupture), were investigated. The results of physico-mechanical tests indicate that the strength characteristics of polyurethane depend on the content and concentration of fillers. It has been found that the polymeric sample filled with 02AgCu nanocomposite (0.2 mmol of Ag and Cu per 1 g of SiO2) has the highest strength of the rupture. It has been shown that the introduction of modified silica leads to a reduction of relative elongation at rupture of polymeric nanocomposite. The highest values showed the sample filled with AgCu (0.1 and 0.12 mmol Ag and Cu, respectively, per 1 g of SiO2). The introduction of silver-containing silica nanocomposites into a polyurethane, containing polyvinylbutiral copolymer fragments, leads to an increase in tensile strength and reduction of relative elongation at rupture. Polymeric composite with 0.5 wt. % of filler had the highest values of physico-mechanical parameters. It has been shown that the thermosphysical characteristics depend on the concentration and composition of the fillers and have a nonlinear character. The synthesized nanocomposites can be effectively used as biomedical materials.

Studies of biodegradability of polyurethane foam (PUF) composite materials with albucid under the influence of biological medium 199 (BM 199) and saline solution for 2 weeks, 1, 3 and 6 months were conducted. IR spectroscopy, physical-mechanical tests, DSC and TGA before and after incubation in model mediums were investigated. It was found that the influence of BM 199 and saline solution on the structure and properties of composite materials with albucid is similar. According to the results of physical-mechanical studies under the influence of model mediums there are processes of biodegradation which are confirmed by a decrease in adhesive strength after incubation in BM 199 and saline solution. According to IR spectroscopy, biodegradation is accompanied by redistribution of hydrogen bonds of NH groups of the polymer matrix. The results of studies by the DSC method indicate a decrease of Tg and increase of ΔСР of PUF composites with albucid compared to the control, which is associated with increasing of segmental mobility of macromolecules under the influence of model mediums and due to the albucid release from polymer matrix. It was found that PUF and PUF composites with albucid in vitro remain heat-resistant materials, because after incubation in BM 199 and a saline solution there is an increase in T0 and Tmax by the TGA method. Studies of the dynamics of albucid release from the PUF matrix were carried out. It was found that the composite materials are capable to the prolonged release of the drug. The amount of released albucid is 36.0 % on the 60th day of the experiment, which does not exceed the therapeutic dose and has no toxic effects. Therefore, polyurethane foam composite materials with albucid can be proposed as promising materials for use as implants with prolonged action of albucid in ophthalmological surgery.

A number of polyurethane ureas (PUUs) containing 1,8-diamino-3,6-dioxooctane (DOODA) in their structure as a macrochain extender were synthesized with a different molar ratio of 4,4'-diaminodiphenylmethane (DADPh) to DOODA as 30:70; 50:50; 70:30. Synthesized polymers are elastic, transparent films with a thickness of 0.3 mm. According to the results of physical and mechanical tests, the tensile strength of the synthesized PUUs is in the range of (0.7-2.0) MPa, and the relative elongation at break is in the range of (73.9-584.7)%. The best physical and mechanical characteristics have the polymer synthesized with a ratio of DADPh:DOODA as 0.3:0.7 with a tensile strength of 2.0 MPa and a relative elongation of 522%. The formation of PUUs was confirmed by the method of IR-spectroscopy. Thermophysical properties synthesized by DSC, TGA methods were studied. It was established that the glass transition temperature (Tg) in a number of synthesized PUUs with DOODA is in the range from (minus) 18.50 °C to (minus) 34.52 °C. An increase in the content of 1,8-Diamino-3,6-dioxaoctane in the PUUs structure leads to a decrease in Tg and a slight increase in ΔCp during the second heating. According to the TGA, the heat resistance characteristics of the synthesized PUUs depend on the content of DOODA. When entering the structure of the PUUs DOODA, a decrease of the temperature of the start of the decomposition (T0) and the temperature of the maximal speed of the decomposition (Tmax), which is non-linear nature. T0 of the synthesized PUUs is in the range (275.16-289.8)°C and is accompanied by a slight loss of mass (0.007-0.093)%. Synthesized PUUs are heat-resistant to a temperature of 275.16 °C, which makes it possible to carry out dry sterilization of samples without changing their characteristics. Synthesized PUUs are promising materials for the immobilization of medicinal substances for further use in medicine.

Background. The development of biocompatible polymeric implant materials and providing them with biological activity is an urgent task that can significantly increase the effectiveness of such materials when used in medical practice. Objective. Investigation of the interaction of connective tissue culture matrix cells with a prolonged form of the proteolytic enzyme lysozyme as part of a polyurethane implant in vitro and study of the effect of this form on cells and tissues during implantation in experimental animals in vivo. Methods. In order to study the possible cytotoxicity of the components of polymer composite materials and the effect of lysozyme on the growth and development of the culture of fibroblastic elements, studies were performed by tissue culture in vitro. Polymeric composite materials based on polyurethaneurea without and with lysozyme were implanted into the body of white laboratory rats of the Wistar line. Cellular responses of the body after implantation were studied by light microscopy by analysis of histological micropreparations. Results. Biological studies have assessed the effect of prolonged lysozyme on cells and tissues in vitro and in vivo. Conclusion. The fibroblast tissue culture method showed the effectiveness of biologically active polyurethaneureas with prolonged release of lysozyme, which was expressed in the prolongation of the dynamics of growth and development of cellular elements in vitro. It has been shown that lysozyme in the composition of polymer composite materials had a biological effect and helped to reduce the cellular response to the implantation of polymer samples, accelerating the formation of connective tissue capsules around the implants.

The influence of the BM 199 model environment on the structure and properties of composite materials with Doxorubicin based on polyurethanes (PU) with isocyanurate branching nodes, in which the content of 2,4,6-triisocyanate(trishexamethylene)isocyanurate (HDT-90) was 0.25.0 , 5, 0.75 mol, and the content of the drug Doxorubicin is 0.5% wt. It was found that the obtained materials exhibit the ability to biodegradation in vitro. In a study by IR spectroscopy of changes in the structure of polyurethane composites with Doxorubicin under the influence of BM 199, it was found that, in the series of polyurethanes, with an increase in the residence time in the model environment, a decrease in the number of weakly bound (νNH 3516 cm-1) and strongly bound bonds of NH groups ( νNH 3515 cm-1), which can occur both due to the biodegradation of the polymer base, and as a result of the release of Doxorubicin. For all the samples under study, during their stay in the biological medium, there is a decrease in the strength at break by 1.5-1.9 times and an increase in the relative elongation by 1.1-1.4 times. According to the data of physical-mechanical tests for all studied materials, the process of biodegradation in vitro is accompanied by an increase in elasticity during the entire study period. According to the results of the study of the dynamics release of Doxorubicin, it was found that from polyurethane composites with isocyanurate branching nodes containing 0.75 mol of HDT-90 in the structure, Doxorubicin is released within 21 days in an amount of 17.6%, which is 4 times more than for samples compositions with 0.5 mole of HDT-90, from which 4.4% of Doxorubicin is released, which may be related to the packing density of the macrochain of the polymer base. Composite materials based on polyurethanes with izocyanurate fragments and Doxorubicin can be proponated for medical and biological tests as material for stem implantation of tissue with prolong medicinal action.

The article is devoted to the development and research of the structure and properties of polyurethane foam (PUF) composite materials with the antibacterial enzyme lysozyme. A series of PUF composite materials with lysozyme of various concentrations (1, 3 and 5 wt %) were obtained. It is established that the immobilization of lysozyme occurs due to intermolecular hydrogen bonds by the method of IR spectroscopy. According to the results of physical-mechanical tests the adhesive strength of polyurethane foam compositions with lysozyme is in the range of 0,82–1,16 MPa. The introduction of lysozyme into the composition of polyurethane foams and an increase its amount causes a decrease in the values of adhesion strength by 18,1–29,3 %. According to differential scanning calorimetry the tested systems are single-phase with a glass transition temperature in the range of -49,20 to -49,86 °C. The introduction of lysozyme into the composition causes an increase heating capacity at the glass transition, which can be associated with a decrease of the packing density of macrochains resulting in an increase in free volume, which leads to an increase molecular mobility. According to the results of the analysis of transmission optical microscopy micrographs the studied PUF have a microporous structure, which depends on the content of filler in their composition. It was found that the presence of lysozyme in the composition of composite materials leads to a decrease in the percentage of porosity, an increase in the number of pores with a diameter of up to 300 μm, which is 76,7–82,4 % (while for PUF – 69,5 %) and the absence of pores with a diameter larger than 990 μm. Thermogravimetric characteristics indicate the heat resistance of the synthesized PUF to a temperature of 179,95 °C, which allows dry sterilization of samples without changing their characteristics. PUF composite materials with lysozyme are promising materials that can be used in medical practice as polymer compositions for the treatment of wounds and burns.

Background. The creation of polymeric composite materials with pronounced biological activity, which are able to act as implants with local prolonged action of the immobilized substance can be widely used in medical practice. Objective. Study of cellular reactions of surrounding tissues of experimental animals to implantation of polymeric composite materials based on isocyanurate-containing polyurethanes with ifosfamide, study of histotoxicity of the obtained materials by tissue culture method. Methods. Polymeric composite materials based on isocyanate-containing polyurethanes without and with ifosfamide were implanted into the body of white laboratory Wistar rats. Cellular responses of the organism and possible changes in the structure of test specimens after implantation were studied by light microscopy by analysis of histological micropreparations. In order to study the peculiarities of the dynamics of growth and development of fibroblastic elements, the method of tissue culture was used. Results. Conducted biological studies by in vivo and in vitro methods allowed to evaluate the effect of immobilized ifosfamide in the structure of isocyanurate-containing polyurethanes on cellular reactions of surrounding tissues during implantation in experimental animals, as well as the effect of extracts from developed polymer samples on cultured cell growth. Conclusion. It was found that the implantation of isocyanurate-containing polyurethanes with ifosfamide led to the development of intense cellular reactions in the area of implant placement, primarily the reaction of round cell elements. The presence of ifosfamide in the structure of the polymeric implantation material probably affected the proliferation of cellular elements, inhibited regenerative processes in the early stages of the study and delayed the formation of a mature connective tissue capsule around the implanted samples. The tissue culture method showed that when making an extract of isocyanurate-containing polyurethanes with ifosfamide in the culture medium, there was a large variability of cell forms, which led to the appearance of macrophage-like elements.

Background: Because the prevalence of ocular trauma in Ukraine remains high, restorative and reconstructive surgeries in the orbit, adnexa, and periorbital area are important; their success, however, depends on the quality of implant materials. Previously, we have developed a polymer material made of cross-linked polyurethane (PU) and containing a biologically active substance, albucid; it seems to be a promising implant material. Purpose: To assess in vitro cytotoxicity and pH of extracts of synthetic polymers made of cross-linked PU composites containing and not containing albucid. Material and Methods: Cell culture methodology was applied to assess in vitro cytotoxicity of cross-linked PU composites containing and not containing albucid. Subcutaneous adipose tissue of albino Wistar rats was used as a source of cells to induce growth of fibroblasts and fibroblast-like cells under culture conditions. The pH value of water solutions was determined through the study of extracts of samples of PU composites containing and not containing albucid. The extracts were examined for pH using the general-purpose pH meter EV-74 supplied with glass pH electrodes. Conclusion: It was demonstrated that fibroblast culture in Carrel flasks with controls as well as in those with extracts of samples of PU composites containing and not containing albucid was in a stable growth phase, indicating no toxic effect of the extracts on cultured cells. Polyurethane composites containing albucid were found to have a neutral pH value, which was within the acceptable range defined by hygiene standards.