Red bone marrow and autologous bone tissue (bone fragments and bone chips) of the donor were harvested intraoperatively during autoplasty of talus bone defect. Titanium chips were obtained by grinding a fragment of a microporous titanium-coated hip arthroplasty (Zimmer). Bone marrow mononuclear cells were isolated in the operating room, and bone and titanium fragments were incubated with a suspension of mononuclear cells. The quality of revitalization was assessed by fluorescence microscopy and histological examination after culturing of adherent cells on the bone and titanium fragments. During culturing on bone chips, bone marrow mononuclear fraction cells demonstrated significantly higher metabolic activity than bone marrow cells (p=0.04). Mononuclear fraction cells were also capable of stable colonization of titanium fragments with the formation of composite tissue model.

Objective: to study the effectiveness of correcting the morphofunctional characteristics of the liver in an experimental model of chronic liver disease (CLD), using implanted cell-engineered constructs (CECs).Materials and methods. Experiments were carried out on male Wistar rats (n = 80) aged 6–8 months with an initial weight of 230–250 g. CLD was modeled by inoculating the rats with 60% CCl4 oil solution for 42 days based on a modified scheme. Microgel based on recombinant spidroin rS1/9 was used as a matrix for CECs fabrication. Allogeneic liver cells (LCs) and multipotent bone marrow-derived mesenchymal stem cells (BM-MSCs) from a healthy donor were used as the cellular component of the CECs. The effectiveness of the corrective effect of the implanted CECs was assessed in an experimental CLD model (n = 60) in two groups of rats: Group 1 (control, n = 20, 1 mL of saline solution was injected into the damaged liver parenchyma) and Group 2 (experimental, n = 40, CECs containing allogenic LCs and BM-MSCs in a 5 : 1 ratio in a volume of 1 mL were implanted into the damaged liver parenchyma). For long-term monitoring of the CEC state, the CECs were labeled by additional inclusion in Cytodex-3. The effectiveness of the regulatory effect of CECs on regenerative processes in the liver was evaluated using biochemical, morphological and morphometric techniques, as well as by flow cytometry at 90 days after implantation.Results. In the control group, the mortality rate in CLD was 25%. There was no death in the experimental group with CLD after CEC implantation. The CECs were found to have a corrective effect on the biochemical and morphological parameters of the liver in CLD during 90 days of follow-up, with concomitant preservation of structural cellular homeostasis in the implanted CECs. Conclusion. Implantation of CECs in the liver facilitates effective correction of CLD by activating regenerative processes in the damaged liver, which is due to long-term preservation of structural cellular homeostasis in the CECs.

Objective. To study the effectiveness and safety of new surgical method for correcting the anterior vaginal wall prolapse using tissue-engineered constructs. Patients and methods. After preliminary experimental work on the creation and evaluation of the biocompatibility of tissueengineered constructs based on non-biodegradable (polypropylene and titanium endoprostheses) mesh implants with an autologous cellular component (rat and human dermal fibroblasts), 4 patients aged 44, 54, 70 and 75 years were examined. Inclusion criteria: anterior vaginal wall prolapse (stage II – III); consent to the installation of tissue-engineered construct. A fourstage surgical program providing for the correction of stage II-III anterior vaginal wall prolapse using tissue-engineered constructs of individual size was used. Results. In the early postoperative period, one patient was diagnosed with a small hematoma of the anterior vaginal wall. During the first month after surgery, one patient complained of gradual perineal pain, another patient – of frequent urination. Subsequently, these symptoms stopped. After 3, 6, 9, 12, 15 months after surgery, during the pelvic examination at rest, the Valsalva maneuver and transperineal ultrasound, no displacement of organs was detected, ultrasound clearly visualized a tissueengineered construct without displacement and deformation. Conclusion. We have developed an original method for correcting the prolapse of the anterior vaginal wall using tissueengineered constructs based on polypropylene and titanium with an autologous cellular component, which helps to optimize the results of surgical treatment, reduce the frequency of disease recurrence and the risk of developing mesh-related complications. Key words: pelvic organ prolapse, tissue-engineered constructs, surgical correction

1НМИЦ стоматологии и челюстно-лицевой хирургии, Москва, e-mail: rasulov.doc@gmail.com; 2Первый Московский государственный медицинский университет им. И.М. Сеченова, Москва; 3Медико-генетический научный центр имени академика Н.П. Бочкова, Москва В настоящее время для изучения метаболической активности клеток при исследовании цитотоксичности и цитосовместимости материалов, как правило, используется МТТ-тест. Однако использование МТТтеста при заселении 3D-матриксов сложной морфологии не всегда показывает достоверные результаты, прежде всего из-за миграции клеток внутрь объема материала. Целью исследования являлась оценка влияния толщины каркаса из микроволокнистого синтетического материала на его цитосовместимость при заселении линейными культурами клеток NIH/3T3 и MCF-7, и использовании стандартного МТТтеста. Нами была проведена обработка результатов оценки эффективности заселения клетками микроволокнистых материалов различной толщины в режимах статического и динамического культивирования. Проведение двухфакторного дисперсионного анализа результатов выявило уменьшение количества выявленных клеток на 30% при заселении материалов толщиной более 250 мкм (p=0,019). Предполагается, что это может быть связано с миграцией клеток вглубь микроволокнистого образца, что приводит к включению формазанового красителя в объем исследуемого материала, делая его недоступным для выявления методами фотометрии. В этом случае для 3D-микроволокнистых материалов требуется использование модифицированного МТТ-теста, основанного на элиминации полимерного каркаса перед растворением формазанового красителя в диметилсульфоксиде (ДМСО). Однако это требует проведения дополнительных исследований для изучения взаимодействия растворителей с формазановым красителем при проведении МТТ-теста. Ключевые слова: МТТ-тест, цитотоксичность, биосовместимость, электроспиннинг, синтетические материалы, поликапролактон.

ВОЗМОЖНОСТИ МОДИФИКАЦИИ МТТ-ТЕСТА ДЛЯ ОЦЕНКИ ЦИТОСОВМЕСТИМОСТИ МИКРОВОЛОКНИСТЫХ СИНТЕТИЧЕСКИХ КАРКАСОВ ПРИ ОБЪЕМНОМ ЗАСЕЛЕНИИ КЛЕТКАМИРасулов Т.С. 1 , Крашенинников М

Objective : to study the viability of a tissue-engineered graft (TEG) based on a devitalized tracheal scaffold (DTS) seeded with mesenchymal stromal and epithelial cells in an experiment on rabbits with assessment of cytocompatibility and biocompatibility in vivo . Materials and methods . Syngeneic mesenchymal stromal bone marrow cells (MSBMCs) and syngeneic lung epithelial cells of rabbit were obtained. The morphology and phenotype of the MSBMC culture were confirmed via immunofluorescence staining for CD90 and CD271 markers. Pulmonary epithelial cells obtained by enzymatic treatment of minced rabbit lung tissue were stained with CKPan, CK8/18 and CK14 markers characteristic of epithelial cells. The donor trachea was devitalized in three successive freezethawing cycles. Double-layer cell seeding of DTS was performed under static and dynamic culturing. Orthotopic implantation of TEGs was performed at the site of the anterolateral wall defect in the rabbit that was formed as a result of tracheal resection over four rings. Results were evaluated by computed tomography, histological and immunohistochemical analyzes. Results . A TEG implant, based on DTS, with bilayer colonization by cell cultures of rabbit MSBMC and epithelial cells was obtained. Three months after implantation, TEG engraftment was noted, no tracheal wall stenosis was observed. However, slight narrowing of the lumen in the implantation site was noted. Six months after implantation, viability of TEG was confirmed by histological method. Epithelialization and vascularization of the tracheal wall, absence of signs of purulent inflammation and aseptic necrosis were shown. The small narrowing of the lumen of trachea was found to have been caused by chronic inflammation due to irritation of the mucous membrane with suture material. Conclusion . A new model for assessing the viability of a tissue engineering implant when closing a critical airway defect was created. The developed TEG – based on DTS seeded (bilayer) by lung epithelial cells and BMSCs – was successfully used to replace non-extended tracheal defects in an in vivo experiment. The use of tracheal tissue-engineered graft for orthotopic implantation showed biocompatibility with minimal tissue response.

Revitalization of decellularized or devitalized matrix scaffolds in tracheal tissue engineering typically involves seeding the autologous recipient cells or allogeneic cells under long-term cultivation. Objective: to study the capability of human nasal chondrocytes for colonization of devitalized scaffolds based on native human tracheal cartilage, with proinflammatory stimulation (cytokine) by adding Interleukin-1-beta (IL-1β) to the culture medium. Materials and methods. Scaffolds for tracheal tissue engineering were obtained from native human tracheal cartilage through devitalization and laser etching. The scaffold was revitalized by seeding the human nasal chondrocytes. Histological examination was performed after staining with hematoxylin and safranin-O, with further microscopy using a Nikon Eclipse L200 light microscope. X-ray microtomography was performed on a Phoenix nanotom m apparatus. Electron microscopy was performed on a Nova NanoSEM 230 setup. Results . There was statistically significant increase in the intensity of colonization (p = 0.0008) with nasal chondrocytes and stimulation of their migration activity (p < 0.0001) in the presence of IL-1β compared with the control groups. Conclusion. Addition of proinflammatory cytokine IL-1β (1 μg/ml) to the culture medium enhances volumetric seeding of devitalized cartilage scaffold with human nasal chondrocytes, allowing to create highly revitalized materials for tracheal tissue engineering.

Background The use of tissue-engineered bone autografts is a promising approach for bone defects restoration. The isolation of cells and their seeding on bone autograft is usually carried out in a laboratory, requiring significant time and two separate surgical interventions. Intraoperative creation of tissue-engineered bone autograft can represent a perspective solution. The aim of this study is to investigate the possibility of creation of tissue-engineered bone autograft by intraoperative enrichment of bone tissue with bone marrow-derived mononuclear cells (BM-MNCs) isolated simultaneously. Methods Red bone marrow and autologous bone tissue (bone fragments and bone chips) of the donor were harvested intraoperatively. BM-MNCs were isolated, and bone fragments were enriched with BM-MNCs intraoperatively. Assessment of the adhesion and proliferation of BM-MNCs on bone fragments was carried out by fluorescence microscopy and histological examination. MTT assay was used to compare metabolic activity of BM-MNCs and wBMA cells seeded on bone chips. Results Autologous bone fragments were colonized with autologous BM-MNCs isolated simultaneously in the O.R. with further adhesion and active growth of cells. When seeded on bone chips, metabolic activity of BM-MNCs was statistically significantly higher compared to wBMA cells (p-value=0.0272) on day 14. There was no difference in metabolic activity of BM-MNCs and wBMA cells cultured in nutrient medium without bone chips. Conclusion Technically simple method of intraoperative enrichment of autologous bone fragments with BM-MNCs isolated simultaneously allowed to create tissue-engineered bone autograft in the O.R. The safety and effectiveness of intraoperatively enriched autografts should be investigated further.

Objective: to study the viability of a tissue-engineered graft (TEG) based on a devitalized tracheal scaffold (DTS) seeded with mesenchymal stromal and epithelial cells in an experiment on rabbits with assessment of cytocompatibility and biocompatibility in vivo. Materials and methods. Syngeneic mesenchymal stromal bone marrow cells (MSBMCs) and syngeneic lung epithelial cells of rabbit were obtained. The morphology and phenotype of the MSBMC culture were confirmed via immunofluorescence staining for CD90 and CD271 markers. Pulmonary epithelial cells obtained by enzymatic treatment of minced rabbit lung tissue were stained with CKPan, CK8/18 and CK14 markers characteristic of epithelial cells. The donor trachea was devitalized in three successive freezethawing cycles. Double-layer cell seeding of DTS was performed under static and dynamic culturing. Orthotopic implantation of TEGs was performed at the site of the anterolateral wall defect in the rabbit that was formed as a result of tracheal resection over four rings. Results were evaluated by computed tomography, histological and immunohistochemical analyzes. Results. A TEG implant, based on DTS, with bilayer colonization by cell cultures of rabbit MSBMC and epithelial cells was obtained. Three months after implantation, TEG engraftment was noted, no tracheal wall stenosis was observed. However, slight narrowing of the lumen in the implantation site was noted. Six months after implantation, viability of TEG was confirmed by histological method. Epithelialization and vascularization of the tracheal wall, absence of signs of purulent inflammation and aseptic necrosis were shown. The small narrowing of the lumen of trachea was found to have been caused by chronic inflammation due to irritation of the mucous membrane with suture material. Conclusion. A new model for assessing the viability of a tissue engineering implant when closing a critical airway defect was created. The developed TEG – based on DTS seeded (bilayer) by lung epithelial cells and BMSCs – was successfully used to replace non-extended tracheal defects in an in vivo experiment. The use of tracheal tissue-engineered graft for orthotopic implantation showed biocompatibility with minimal tissue response.

Revitalization of decellularized or devitalized matrix scaffolds in tracheal tissue engineering typically involves seeding the autologous recipient cells or allogeneic cells under long-term cultivation. Objective: to study the capability of human nasal chondrocytes for colonization of devitalized scaffolds based on native human tracheal cartilage, with proinflammatory stimulation (cytokine) by adding Interleukin-1-beta (IL-1β) to the culture medium. Materials and methods. Scaffolds for tracheal tissue engineering were obtained from native human tracheal cartilage through devitalization and laser etching. The scaffold was revitalized by seeding the human nasal chondrocytes. Histological examination was performed after staining with hematoxylin and safranin-O, with further microscopy using a Nikon Eclipse L200 light microscope. X-ray microtomography was performed on a Phoenix nanotom m apparatus. Electron microscopy was performed on a Nova NanoSEM 230 setup. Results. There was statistically significant increase in the intensity of colonization (p = 0.0008) with nasal chondrocytes and stimulation of their migration activity (p < 0.0001) in the presence of IL-1β compared with the control groups. Conclusion. Addition of proinflammatory cytokine IL-1β (1 μg/ml) to the culture medium enhances volumetric seeding of devitalized cartilage scaffold with human nasal chondrocytes, allowing to create highly revitalized materials for tracheal tissue engineering.

Aim: to determinate the most effective liver cells and multipotent mesenchymal stromal cells of bone marrow (MMSC BM) ratio into implantable cell engineering constructions (CECs) used for chronic liver failure (CLF) correcting.Materials and methods. For creating liver CECs it was used a biopolymer implant – a composition of a heterogeneous collagen-containing gel (BMCG) (Sphero®GEL trademark) containing viable liver cells and MMSC BM in the following ratios – 1 : 1; 5 : 1 and 10 : 1 respectively. CECs with different ratios of liver cells and MMSC BM were implanted into liver of rats in which chronic liver failure (CLF), was modeled by using CCl4. The effectiveness of the regulatory effects of CECs (with different cell ratios) on regenerative processes in livers were assessed by using biochemical, morphological and morphometric methods at different periods after their implantation.Results. Corrective effect of CECs with different cell composition on biochemical and morphological parameters of livers at chronic liver failure was established. During studying the liver CECs with various cell ratios of liver cells and MMSC BM (1 : 1; 5 : 1 and 10 : 1 respectively), it was found that the most optimal ratio of cells into the CECs is 5 : 1, because at this ratio of cells, there were a more distinct normalization of the morphological and functional liver parameters within 365 days after modeling CLF and maintenance of the structural homeostasis into the CECs. Themselves, which allows predicting their long-term regulatory effect on the liver tissue in CLF and maintaining its normal structural and functional state.Conclusion. The effective correction of chronic liver failure can be carried out by using the implanted liver CECs, in which donor liver cells and MMSC BM where presented in ratios – 1 : 1; 5 : 1 and 10 : 1. But analysis of prolonged correction of liver morphological and functional parameters at CECs using it was allow to recommend the preferences using of CECs with ratio 5 : 1, because prolonged preservation of structural homeostasis into these CECs makes possible to prognosticate their prolonged regulatory action on the liver tissue at CLF, especially for recipients on a waiting list for liver transplantation.

Aim: to determinate the most effective liver cells and multipotent mesenchymal stromal cells of bone marrow (MMSC BM) ratio into implantable cell engineering constructions (CECs) used for chronic liver failure (CLF) correcting. Materials and methods. For creating liver CECs it was used a biopolymer implant – a composition of a heterogeneous collagen-containing gel (BMCG) (Sphero®GEL trademark) containing viable liver cells and MMSC BM in the following ratios – 1 : 1; 5 : 1 and 10 : 1 respectively. CECs with different ratios of liver cells and MMSC BM were implanted into liver of rats in which chronic liver failure (CLF), was modeled by using CCl4. The effectiveness of the regulatory effects of CECs (with different cell ratios) on regenerative processes in livers were assessed by using biochemical, morphological and morphometric methods at different periods after their implantation. Results. Corrective effect of CECs with different cell composition on biochemical and morphological parameters of livers at chronic liver failure was established. During studying the liver CECs with various cell ratios of liver cells and MMSC BM (1 : 1; 5 : 1 and 10 : 1 respectively), it was found that the most optimal ratio of cells into the CECs is 5 : 1, because at this ratio of cells, there were a more distinct normalization of the morphological and functional liver parameters within 365 days after modeling CLF and maintenance of the structural homeostasis into the CECs. Themselves, which allows predicting their long-term regulatory effect on the liver tissue in CLF and maintaining its normal structural and functional state. Conclusion. The effective correction of chronic liver failure can be carried out by using the implanted liver CECs, in which donor liver cells and MMSC BM where presented in ratios – 1 : 1; 5 : 1 and 10 : 1. But analysis of prolonged correction of liver morphological and functional parameters at CECs using it was allow to recommend the preferences using of CECs with ratio 5 : 1, because prolonged preservation of structural homeostasis into these CECs makes possible to prognosticate their prolonged regulatory action on the liver tissue at CLF, especially for recipients on a waiting list for liver transplantation.

Revitalization of decellularized or devitalized scaffolds for trachea tissue engineering normally involves a seeding of autologous cells of recipient or allogeneic cells on the scaffold. Aim: aimed to investigate the capability of human nasal chondrocytes for colonization of devitalized scaffolds, based on the native human tracheal cartilage, with the proinflammatory stimulation by adding of Interleukin-1-beta (IL-1 beta) to the culture medium. Materials and methods. Scaffolds for trachea tissue-engineering were generated from native human tracheal cartilage by devitalization and laser-engraving. For the purpose of scaffold-revitalization a cell-seeding with human nasal chondrocytes was performed. Following histological examination was done with Hematoxylin & Safranin-O stainings and light microscopy. X-ray microtomography and scanning electron microscopy were performed additionally. Results. Statistically significant increase in the colonization rate (p = 0.0008) with nasal chondrocytes and stimulation of their migration activity (p < 0.0001) in the presence of IL-1 beta compared to the control group were confirmed. Conclusion. Presence of the inflammatory cytokine IL-lb (1 mu g/ml) in the culture medium enhances volume seeding of devitalized cartilage scaffold with human nasal chondrocytes, allowing to create high-revitalized materials for trachea tissue engineering.

The aim of the study was to evaluate the effect on angiogenesis of a biocompatible, biodegradable material-derived scaffold implanted into rats and functionalized using a plasmid with a vascular growth factor gene. Methods. Experiments were performed on 24 female Wistar rats aged 2 months weighing 180-200 g. We investigated 1 cm x 1 cm flat scaffolds obtained by electrospinning from polycaprolactone functionalized scaffolds with a VEGF-165 plasmid (gene therapy drug, Neovasculgen) incorporated inside the fibers at two concentrations, low (0.005 mg/ml) and high (0.05 mg/ml). The sample and control were simultaneously implanted subcutaneously into two formed symmetrical pockets in the interblade zone. At 7, 16, 33, 46, and 64 days, the scaffolds were removed, and histological examination was performed; the tissue reaction was studied including morphometric evaluation of density and diameter of blood vessels in the implantation area, and the area of the image occupied by the material was measured. Results. Tissue rejection was absent after implantation of either control or modified material. When the material was exposed in vivo, besides resorption of the material, blood vessel number and diameter changed. As the Neovasculgen concentration in samples increased, a dose-dependent effect of angiogenesis stimulation became evident. Vascular density was increased by 46% (high concentration, 33 days) in functionalized matrices compared to the control. After cessation of the drug treatment, the vascular density approached the control values. Conclusion. The developed technique for functionalizing polymeric scaffolds by administration of a solution of the gene therapy drug, Neovasculgen, into microfibers provides a prolonged and dose-dependent effect on growth of blood vessels in the implantation zone.

Цель исследования - оценка влияния на ангиогенез конструкций из волокнистого поликапролактона, модифицированного плазмидой с геном сосудистого фактора роста, при имплантации крысам. Методика. Эксперименты выполнены на 24 крысах-самках Вистар в возрасте 2 мес, массой 180-200 г. В работе исследовали плоские каркасы размером 1 см х 1 см, полученные методом эмульсионного электроспиннинга из раствора поликапролактона. Материал каркасов витализировали плазмидой VEGF-165 (геннотерапевтический препарат Неоваскулген), введенной внутрь двух типов волокнистых материалов в разных концентрациях: низкой - 0,005 мг/мл, и высокой - 0,05 мг/мл. Образец и контроль (материал без витализации) одномоментно имплантировали подкожно в два сформированных симметричных кармана в межлопаточной зоне. Окружающие каркас ткани на 7-е, 16-е, 33-и, 46-е и 64-е сутки извлекали, проводили гистологическое исследование: изучали тканевую реакцию с морфометрической оценкой плотности распределения и диаметра сосудов в области имплантации, а также оценивали степень биодеградации волокнистого материала. Результаты. Признаков тканевой реакции отторжения при имплантации как контрольного, так и модифицированного материала не выявлено. Показано, что при экспозиции материала in vivo наряду с резорбцией материала происходят изменения количества и диаметра сосудов. Выявлен дозозависимый эффект стимуляции ангиогенеза при увеличении концентрации Неоваскулгена в образцах. Для витализированных материалов отмечено увеличение плотности распределения сосудов на 46% (высокая концентрация, 33-и сут) по сравнению с контролем. После прекращения воздействия препарата, плотность распределения сосудов приближалась к значениям в контроле. Заключение. Разработанная методика витализации полимерных каркасов с внесением раствора геннотерапевтического препарата Неоваскулген внутрь микроволокон обеспечивает пролонгированный и дозозависимый эффект на рост сосудов в зоне имплантации. The aim of the study was to evaluate the effect on angiogenesis of a biocompatible, biodegradable material-derived scaffold implanted into rats and functionalized using a plasmid with a vascular growth factor gene. Methods. Experiments were performed on 24 female Wistar rats aged 2 months weighing 180-200 g. We investigated 1 cm x 1 cm flat scaffolds obtained by electrospinning from polycaprolactone functionalized scaffolds with a VEGF-165 plasmid (gene therapy drug, Neovasculgen) incorporated inside the fibers at two concentrations, low (0.005 mg/ml) and high (0.05 mg/ml). The sample and control were simultaneously implanted subcutaneously into two formed symmetrical pockets in the interblade zone. At 7, 16, 33, 46, and 64 days, the scaffolds were removed, and histological examination was performed; the tissue reaction was studied including morphometric evaluation of density and diameter of blood vessels in the implantation area, and the area of the image occupied by the material was measured. Results. Tissue rejection was absent after implantation of either control or modified material. When the material was exposed in vivo , besides resorption of the material, blood vessel number and diameter changed. As the Neovasculgen concentration in samples increased, a dose-dependent effect of angiogenesis stimulation became evident. Vascular density was increased by 46% (high concentration, 33 days) in functionalized matrices compared to the control. After cessation of the drug treatment, the vascular density approached the control values. Conclusion. The developed technique for functionalizing polymeric scaffolds by administration of a solution of the gene therapy drug, Neovasculgen, into microfibers provides a prolonged and dose-dependent effect on growth of blood vessels in the implantation zone.

Development of the tissue-engineered graft for repair of bile duct injures. Iatrogenic bile duct injury is still a challenge for surgeons. Up to 2.7-0.05% of patients are require to reconstructive bile duct surgery after cholecystectomy. The standard surgery includes suturing of the duct with small intestine, but this reconstruction can lead to various complications. No one method was proposed as the best option for the repair and native reconstruction of common bile duct, though the use of bioengineered materials and methods is keeping an experimental surgical research. We have constructed a multilayered tube consisting of three synthetic polymers layers and two types of cells: bone marrow mesenchymal stem cells (MSCs) and bile duct epitheliocytes. All polymers were tested for biocompatibility with the use of two cell lines: fibroblasts 3T3 and epitheliocytes MCF7 cells. The inner layer was formed with bile duct epitheliocytes and PCL modified by EGF during a electrospinning fabrication, which allows to stimulate a proliferations of epitheliocytes. The medium layer was formed by PCL thin film. The outer layer of the tube included a copolymer PCL/PLGA (70:30) with seeded MSCs. The copolymer was modified with VEGF165 plasmid (Neovasculgen TM ), which increased of angiogenesis by 70% after subcutaneous implantation in rats. The same Neovasculogen TM -modified fibrous PCL increased angiogenesis by 46%. The construct is biodegradable in various model mediums: deionized water, phosphate buffer, bile, full culture medium. The next step is pre-clinical trials on rabbits and minipigs for assessment of implantation safety and efficacy. We suppose that this tubular multilayered tissue-engineered construct will be capable of integration after implantation and may be used to reconstruct damaged bile ducts.