Russian Journal of Transplantology and Artificial Organs
Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation
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Emerging genetic markers in clinical transplantation: current research and future directions
Outcomes of liver transplantation in incidentally diagnosed combined Hepatocellular-Cholangiocarcinoma: A 25-year single-center matched cohort study
Background and aim. Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare liver malignancy, which comprises clinical and morphological features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) and corresponds to 1–4.7% of cases of primary liver carcinomas. At present, Liver transplantation (LT) is not routinely recommended for known cHCC-CCA due to concerns regarding aggressive behavior and recurrence risk. However, incidental diagnoses after LT performed for presumed HCC raise questions regarding post-transplant outcomes. Material and methods. We conducted a retrospective single-center study including patients who underwent LT between 2000 and 2025. Patients with incidentally diagnosed cHCC-CCA on explant pathology were matched 1 : 2 with HCC controls according to age, year of transplantation, donor type, tumor burden at explant (number and size), lymphovascular invasion, locoregional therapy, and BAR score. Overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan–Meier estimates and compared with the log-rank test. Results. After matching, 9 patients with cHCC-CCA were matched with 18 HCC controls. Five-year OS was 41.7% in the cHCC-CCA group and 81.5% in the HCC group (p = 0.26) and Five-year DFS was 70% versus 85.9%, respectively (p = 0.25). Recurrence occurred in two patients in each group. To date, this 25-year study represents one of the most rigorously matched European analyses, uniquely incorporating lymphovascular invasion and BAR score as matching variables. Conclusions. Despite the fact that no statistically significant differences were demonstrated in post-transplant survival or recurrence between the groups, worse results could be observed in the studied group, which is consistent with the current non-indication of LT for cHCC-CCA. This study was substantially underpowered, so the absence of statistical significance should not be interpreted as clinical equivalence.
Clinical course of HCV-associated liver cirrhosis after viral eradication in transplant candidates
Objective: to investigate markers of liver injury ( MELD-Na and Child–Turcotte–Pugh [CTP] scores) before and after treatment with direct-acting antiviral (DAA) therapy, and to characterize clinical outcomes of HCV-associated decompensated liver cirrhosis following viral eradication in liver transplant (LT) candidates. Materials and methods. A prospective comparative study was conducted in 320 patients with decompensated cirrhosis listed for LT. Demographic, clinical, and laboratory parameters were analyzed, including MELD-Na and CTP scores, severity of hepatic encephalopathy, ascites, number of bleeding episodes, and occurrence of complications. Assessments were performed prior to HCV therapy and 12 months after achieving sustained virologic response (SVR). Subgroup analyses included patients who transitioned to compensated cirrhosis (n = 113) and those who remained or progressed to decompensated cirrhosis (n = 207). Cumulative risks were evaluated using Cox proportional hazards regression in univariate and multivariate models. Results. After 12 months of follow-up following the achievement of SVR, significant increases were observed in white blood cell and platelet counts, as well as serum albumin levels. In parallel, creatinine, international normalized ratio (INR), and bilirubin levels decreased. There was also a reduction in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, along with improvements in the severity of ascites and hepatic encephalopathy, a decrease in the number of bleeding episodes, and lower CTP and MELD-Na scores. Predictors of further decompensation of cirrhosis included decreased serum sodium level, increased severity of liver injury on CT imaging, greater severity of ascites and hepatic encephalopathy, and a higher number of complications during follow-up.
Epidemiology of malignant tumors in kidney transplant recipients (a literature review)
Kidney transplant recipients face a significantly higher risk of developing malignant tumors. For certain tumor types, incidence rates are hundreds of times higher than in the non-transplant population. Overall cancer incidence and patterns vary significantly across countries, reflecting geographically specific risk factors. This literature review examines the epidemiological characteristics of post-transplant malignancies occurring in kidney transplant recipients worldwide.
Sleeve gastrectomy in a patient with morbid obesity following liver transplantation
Objective: to present a clinical case of laparoscopic sleeve gastrectomy (LSG) performed for morbid obesity following liver transplantation (LT). Materials and methods. A female patient (born 1968) with primary biliary cirrhosis underwent orthotopic LT in 2019. Three years later, she required anterior abdominal wall repair for a postoperative hernia. Subsequently, progressive weight gain and deterioration in quality of life were observed. Despite significant intra-abdominal adhesions, LSG was performed. The postoperative period was uneventful. Results. The patient demonstrated significant weight loss, improved quality of life, and preserved graft function. Conclusion. LSG is an effective treatment for morbid obesity and its associated complications following LT.
Living-related kidney transplantation in a patient with Bardet-Biedl syndrome
Background. Bardet–Biedl syndrome (BBS) is a hereditary diencephalic-retinal disorder characterized by a combination of clinical features, including obesity, mental retardation, retinal degeneration, brachydactyly, polydactyly, hypogenitalism, and renal dysfunction. Up to 25% of patients develop end-stage chronic renal failure requiring renal replacement therapy or kidney transplant (KT), often during childhood. Objective: to present the treatment outcomes of severe chronic renal failure in a 16-year-old female patient with the rare genetic condition BBS, who previously underwent KT from a related donor at the age of 6. Materials and methods. A retrospective analysis was conducted of the patient’s medical records, including the clinical course of the disease, laboratory and instrumental findings, and details of the treatment provided to the 16-year-old patient diagnosed with BBS. Results. On November 25, 2015, an AB0-compatible related (the patient’s father) KT was performed on the right side. Maintenance immunosuppressive therapy included tacrolimus, mycophenolic acid, methylprednisolone. Immediate graft function was observed after the surgery. At the follow-up consultation on November 13, 2024, the patient was receiving tacrolimus (Prograf) 1.5 mg twice daily, mycophenolic acid 180 mg twice daily, methylprednisolone 4 mg per day orally, as well as Cardiomagnyl and Omeprazole 20 mg orally. Laboratory findings showed a serum creatinine level of 65.9 μmol/L, with an estimated glomerular filtration rate calculated using the CKD-EPI equation of 119.72 mL/min/1.73 m2. Conclusion. Despite the presence of severe congenital pathologies associated with BBS, this clinical case presents a successful KT with minimal complications in both the early and long-term postoperative periods.
A new risk-balanced donor–recipient matching model incorporating individual characteristics in kidney transplantation
Objective: to improve kidney transplant (KT) outcomes by developing a risk-balance donor–recipient matching algorithm, with individualized immunosuppressive therapy, and to evaluate its efficacy and safety compared with the standard approach. Materials and methods. The study included 712 KT recipients. Group I (n = 472) comprised patients who underwent transplantation between 2018 and 2023 using the standard donor allocation and immunosuppression approach. Group II (n = 240) included recipients transplanted between 2024 and 2025 following the implementation of the new matching model. The proposed model stratifies recipients by immunological risk and aligns them with appropriate donor types, avoiding combinations of marginal donor organs with high-risk recipients. Based on risk stratification, modified induction immunosuppressive regimens and administration of calcineurin inhibitors were applied. The primary endpoint was the incidence of delayed graft function. Secondary outcomes included rates of infectious complications, acute rejection, length of hospital stay, and length of stay in the intensive care unit. Results. The incidence of delayed graft function was significantly lower in Group II compared with Group I (17.5% vs 37.1%, p < 0.001). Infectious complications were also reduced (6.3% vs 13.1%, p = 0.007). The median length of hospital stay decreased from 19 to 15 days (p < 0.001). No statistically significant differences were observed between the groups in terms of acute rejection rates or length of stay in the intensive care unit. Conclusion. The implementation of a risk-balanced donor–recipient matching algorithm, combined with personalized immunosuppressive therapy, substantially reduced the incidence of delayed graft function without increasing the risk of acute rejection.
Emergency heart transplantation in a female patient with acute coronary syndrome caused by pregnancy-associated spontaneous coronary artery dissection: a clinical case
Although spontaneous coronary artery dissection (SCAD) is a rare condition, it should be considered in young women presenting with acute coronary syndrome during the peripartum period. A multidisciplinary approach is essential: timely collaboration among cardiologists, cardiac surgeons, intensivists, and transplant specialists allows for the consideration of heart transplantation (HT) as a last-resort, yet potentially life-saving, intervention in cases of refractory heart failure. Thus, HT expands therapeutic options for managing life-threatening cardiac conditions in obstetric practice. The presented clinical case demonstrates the successful use of heart transplantation as a definitive treatment in a 30-year-old woman with pregnancy-associated SCAD (P-SCAD), following unsuccessful attempts at revascularization, including stenting, balloon angioplasty, and mechanical circulatory support.
Diagnosis of cardiac allograft vasculopathy using optical coherence tomography
Objective: to determine the prevalence of cardiac allograft vasculopathy (CAV), detected by optical coherence tomography (OCT), in patients after orthotopic heart transplantation (OHT), and to analyze its impact on clinical outcomes. Materials and methods. The single-center retrospective cohort study analyzed data from patients who underwent OHT between 2013 and 2024. Patients who died within 30 days after transplantation were excluded from the analysis. All recipients underwent coronary angiography during the first week after transplantation to detect baseline coronary lesions in the donor heart. Subsequently, routine angiographic screening was performed. When lesion progression or development of de novo stenoses was suspected, additional evaluation using OCT was carried out to assess lesion morphology. Based on OCT results, recipients were divided into two groups: patients with and without CAV. The study endpoints included myocardial infarction, myocardial revascularization, cardiac death, and a decrease in left ventricular ejection fraction (LVEF) during follow-up. Results. The study included 66 patients. Coronary artery disease was detected in 15 patients (22.72%) during angiographic screening. However, subsequent assessment using OCT confirmed CAV in only 10 recipients (15.15%). In all confirmed cases, the left anterior descending (LAD) artery was involved. Among patients with pre-existing coronary lesions, the median time to the first angiographic detection was 3.5 months, compared with 25 months in recipients without baseline lesions. In the CAV group, myocardial infarction occurred in 4 patients (40.0%), whereas no ischemic events were observed in the non-CAV group (p < 0.001). Myocardial revascularization was required in 7 patients (70.0%) with CAV, while in the group without this condition, only one procedure was performed for an initial lesion of the LAD artery (p = 0.005). Median LVEF in the CAV group decreased from 66.0% to 57.5%, whereas no significant changes in left ventricular systolic function were observed in patients without CAV (p = 0.045). Conclusion. OCT enables reliable, early detection of CAV. In all confirmed cases, the lesions were localized around the LAD artery. CAV developed earlier in recipients with pre-existing coronary atherosclerosis. Moreover, the presence of CAV was associated with an increased risk of myocardial infarction and the need for coronary revascularization, which was accompanied by a decline in LVEF and subsequent development of heart failure.
Hemolysis testing of a small-sized axial flow pump for implantation in patients with low anthropometric parameters
The Biotechnical Systems Laboratory assessed the trauma potential of a newly developed pediatric implantable axial flow pump. A mathematical evaluation was performed to assess shear stress, blood exposure time, and the hemolysis index. Regions contributing to blood trauma were identified at flow rates ranging from 1.5 to 2.5 L/min. A standardized methodology was developed and applied to evaluate blood cell damage (hemolysis) under simulated pediatric hemodynamic conditions, with a pressure gradient of 85 ± 5 mm Hg and three flow rates of 1.5, 2.0, and 2.5 L/min. The operation of the compact implantable axial pump prototype under left ventricular assist conditions was designed to account for the anthropometric characteristics of patients with a body surface area of less than 1.2 m2. Hemolysis tests were performed using a hydrodynamic test bench that ensures continuous circulation of donor blood. The testing protocol involved measuring the concentration of free hemoglobin in plasma samples collected during pump operation on the test bench. Based on these measurements, hemolysis and modified hemolysis indices were calculated, demonstrating positive performance dynamics of the pump under the tested conditions.
Nanostructural organization of skeletal muscle myocytes revealed by scanning probe nanotomography
Objective: to perform a statistical analysis of the angular orientations of hexagonal myofilament lattices in rat skeletal muscle myofibrils using scanning probe nanotomography (SPN). Materials and methods. Skeletal muscle tissue samples were obtained from healthy Wistar rats for the study. Specimens of rat lumbar skeletal muscle fibers were embedded in epoxy resin. After sectioning with an ultramicrotome, the specimen surfaces were examined using SPN. Analysis of the resulting images of sarcomere cross-sections enabled the determination of the angular orientations of the hexagonal lattices formed by myosin myofilaments. Results. A method was developed to calculate the angular orientations of hexagonal lattices based on moiré patterns observed in images of sarcomere cross-sections. Statistical analysis of the obtained images showed that the relative rotations of the hexagonal lattices do not follow a normal distribution according to the Kolmogorov–Smirnov test (p = 0.3). The results indicate that the orientations of the lattices vary randomly along the myofibrils. Conclusion. Analysis of lattice orientations in adjacent sarcomeres made it possible, for the first time, to obtain and statistically evaluate data on their mutual orientations along myofibrils. The results revealed a low degree of alignment in the orientations of myosin filaments within myofibrils of rat skeletal muscle. The proposed methods and algorithms may be further applied to studies of the nanostructural organization of myocytes and cardiomyocytes in different species.
T cells as regulators of angiogenesis (a literature review)
T cells not only provide cellular immunity, but also exert control over the proliferation, differentiation, and maturation of cells across diverse target tissues, thereby regulating both physiological and reparative regenerative processes. Evidence demonstrates that these cells contribute to the restoration of parenchymal organ structures, promote osteogenic differentiation of mesenchymal stem cells, activate neurogenesis, and modulate myogenesis and angiogenesis. This review focuses on the mechanisms by which T cells regulate reparative processes within the vascular system, highlighting key aspects such as cell–cell interactions between T cells and endothelial cells, the role of chemokine receptors in mediating T-cell adhesion to the endothelium, and their capacity to synthesize angiogenic growth factors including interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), tumor necrosis factor-α (TNF-α), insulin-like growth factor-1 (IGF-1), amphiregulin, and a broad range of interleukins. The review also describes the ability of T cells to control post-transcriptional regulation of gene expression in endothelial cells through small non-coding RNA molecules (miRNAs). Specifically, information is provided on the angiogenic roles of miRNAs previously identified in T cells: miR-16, miR-21, miR-25, miR-150, miR-155, miR-181, and miR-451, and the mechanisms through which they mediate these effects.
Biological safety and therapeutic efficacy of a biopolymer-based multicomponent hydrogel mimicking the extracellular matrix
Background. The development of adhesive wound dressings with regenerative properties for restoring the integrity of damaged skin and mucous membranes is currently a priority area in regenerative medicine and tissue engineering. Objective: to develop a homogeneous, multicomponent collagen-based biopolymer adhesive hydrogel (MCBAH) and to evaluate its safety and efficacy. Materials and methods. Sterile samples of MCBAH were analyzed. The content of volatile organic compounds (VOCs) was determined using a Chromatec-Crystal 5000 gas chromatograph (Chromatec SKB CJSC, Russia). Osmolarity was measured using the Osmometer K-7400 liquid analyzer (Knauer, Germany), and pH was determined with the pH-150MI pH meter (Izmeritel’naya Tekhnika LLC, Russia). Biological safety was assessed in accordance with GOST ISO 10993 and included evaluation of cytotoxicity, pyrogenicity, material-mediated effects, general toxicity (acute and subchronic), as well as sensitizing and irritant effects. In vitro cytotoxicity was assessed using cultures of NIH/3T3 fibroblasts (ATCC® CRL-1658™). The efficacy of MCBAH was evaluated in a rat thermal burn model. Histological examinations were performed on tissues from the heart, lungs, thymus, liver, spleen, kidneys, adrenal glands, gonads, and cerebral cortex. Results. VOCs concentrations did not exceed permissible limits. Osmolarity was 334 ± 20 mOsm/kg, and pH was 7.18 ± 0.11. In vitro studies demonstrated the absence of cytotoxicity. Acute toxicity testing revealed no toxic effects in laboratory animals. Similarly, subchronic toxicity studies showed that exposure to MCBAH did not cause intoxication or mortality. No delayed-type hypersensitivity reactions were observed, indicating the absence of a sensitizing effect. Intradermal administration of MCBAH and its application to the mucous membranes of the hamster cheek pouch, rabbit vagina, and rabbit rectum produced no detectable response, with an irritation index of 0. Following intravenous administration of extracts from MCBAH samples to rabbits, increase in body temperature in all three animals did not exceed 0.1 °C, indicating that the biomimetic hydrogel does not induce a pyrogenic response. Conclusion. In a rat thermal burn model, application of an adhesive biomimetic hydrogel mimicking the extracellular matrix (ECM) immediately after burn induction and daily until complete wound closure significantly accelerated wound healing in the experimental group by 15.3 ± 7.7% (34.9 days) compared with the control group (40.2 days, p < 0.01). Treatment also promoted the formation of a fully developed epithelial layer and accelerated restoration of the original histological structure of the damaged skin. These findings support further investigation of the efficacy of this hydrogel in experimental models of damaged mucous membranes.
Nanostructural analysis of 3T3 mouse fibroblasts cultured on natural silk-based tissue scaffolds in vitro
Objective: to perform a nanostructural analysis of the interaction between mouse 3T3 fibroblasts and natural silk-based tissue scaffolds in vitro using scanning probe nanotomography (SPN). Materials and methods. Two types of natural silk tissue scaffolds were investigated: Fibroplen-Atlas and Fibroplen-Gaz, along with their modified variants, Fibroplen-Atlas 80 and Fibroplen-Gaz 80. Mouse 3T3 fibroblasts were cultured on the scaffolds for 7 days. Following incubation, scaffold–cell constructs were fixed and embedded in epoxy resin. Ultrathin sections were prepared using an ultramicrotome, and the sample surfaces were analyzed by SPN. The acquired data enabled quantitative assessment of key morphological parameters of the cells, the scaffolds, and the interfaces between them. Results. Analysis of the acquired images revealed thinning and fragmentation of microfibers within the strands of the modified scaffolds (Fibroplen-Atlas 80 and Fibroplen-Gaz 80). In contrast to the unmodified scaffolds, fibroblasts in the modified matrices interacted with both the inner and outer surfaces of the microfibers. This enhanced interaction resulted in a marked increase (up to 40%) in the proportion of the cell surface area in contact with the scaffold surface. Conclusion. Nanostructural analysis of mouse 3T3 fibroblasts cultured on natural silk-based tissue scaffolds provided detailed insights into the topological and morphological features of cell–scaffold interactions in both modified and unmodified matrices. Enhanced interaction between cells and microfibers within the modified scaffold strands may promote accelerated scaffold biodegradation. The combined nanostructural findings and in vitro cell culture results indicate that the developed scaffolds effectively support 3T3 cell adhesion and the formation of stable cell–matrix contacts.
Effects of allogeneic and xenogeneic biomaterials on macrophage morphology and function in vitro and in vivo
Background. Determining the biocompatibility of biotransplants remains a pressing issue in tissue engineering. The degradation products of these materials elicit diverse cellular responses that ultimately influence healing outcomes. Among these responses, macrophages play a central role in regulating biocompatibility and guiding the regenerative process. Objective: to characterize the cellular composition and repertoire of macrophages induced by exogenous allogeneic and xenogeneic matrices, and to determine the morphofunctional profile of macrophages in vitro and in vivo following allogeneic and xenogeneic transplantation. Materials and methods. In vitro, donor-derived monocytes were cultured for 7 days on a substrate composed of a sponge matrix and a suspension of dispersed allogeneic biomaterials from the Alloplant® series, obtained from human cadaver tissue. In vivo, male outbred rats (200–250 g; n = 20) received subcutaneous injections of a suspension (10 mg) of dispersed allogeneic biomaterial (DAB) derived from rat tendons, and dispersed xenogeneic biomaterial (DXB) derived from rabbit tendons. Transplantation sites were excised at 7 and 14 days post-implantation. Morphological evaluation included histological and immunohistochemical analyses (VEGF-R1, CD206, CD86, TNF-α, CD163, TGF-β, CD68, FGF-1, MMP-9, TIMP-2, HLA-DR), as well as scanning electron microscopy. Results. In vitro, monocytes differentiated into mature macrophages exhibiting the following phenotype: CD68+, CD206+, VEGF-R+, CD86–, TGF-β–, CD163–, FGF-1–, MMP-9–, and TIMP-2–. In vivo, DAB underwent lysis with the release of glycosaminoglycans (GAG), followed by resorption and replacement without evidence of encapsulation by macrophages of the following phenotypes: M1 (CD86+) and M2 (CD206+, CD163+), as well as VEGF-R+ and TNF-α+ expression, while remaining negative for TGF-β and HLA-DR. In contrast, DXB induced encapsulation and granulomatous inflammation, with no detectable GAG release. Macrophages in this group predominantly exhibited an M2 phenotype (CD206+), with positive expression of TGF-β and HLA-DR, and negative expression of TNF-α and VEGF-R. Conclusion. The species specificity of biomaterials determines macrophage phenotype, cellular response, and healing outcomes. Allogeneic biomaterial was effectively resorbed and replaced by structurally complete regenerative tissue. Macrophages of both M1 and M2 phenotypes did not demonstrate antigenic or fibrogenic activity and promoted angiogenesis. In contrast, xenogeneic biomaterial elicited chronic inflammation and encapsulation, characterized by the presence of M2 macrophages with antigenic and fibrogenic properties.
Therapeutic potential of stem cell and cell-free therapies for acute and chronic kidney failure
Despite the global increase in the number of patients requiring care for end-stage chronic kidney disease (CKD), the demand for renal replacement therapy continues to exceed healthcare capacity. This gap underscores the need for innovative strategies to prevent the progression of acute kidney injury (AKI) to CKD. One promising approach is stem cell (SC) therapy, involving cells derived from various tissues or their secretory products (SC secretome). This review examines current evidence on the potential of cell-based therapies to promote regeneration of damaged renal structures by enhancing adaptive and compensatory mechanisms and suppression of maladaptive responses in kidney injury. Experimental studies demonstrate that SC therapy significantly improves renal function, accelerates recovery in AKI, and reduces the risk of progression to CKD. Notably, SC secretome therapy appears to be comparably effective to the use of stem cells themselves. Factors limiting the efficacy of cell therapy and potential strategies to overcome these challenges are also discussed.
Comparative efficacy of intact and apoptotic bone marrow cells at different stages of type 2 diabetes progression
Objective: to compare the therapeutic efficacy of intact and apoptotic bone marrow mononuclear cells (BMMCs) at different stages of type 2 diabetes mellitus (T2D) progression. Materials and methods. The study was conducted using a genetic model of T2D in db/db mice (n = 52; age 0.5–1.0 months). Animals were divided into four groups: control (n = 10) and three experimental groups (n = 14 each), which received allogeneic BMMCs from healthy donors at a dose of 40–45 × 106 cells at different stages of disease progression (1, 3, and 7 months of age). Each experimental group was further subdivided into two subgroups: one receiving freshly isolated intact BMMCs (iBMMCs) and the other apoptotic BMMCs (aBMMCs). Apoptotic cells were obtained by incubating intact cells in Bradschneider’s ion-balanced preservative solution to induce reversible apoptosis. Outcomes were assessed by measuring blood glucose levels, body weight, total oxidative metabolism index (TOM), and histological liver changes. Reliability of the results was assessed using statistical methods on a personal computer, employing the Shapiro–Wilk test and the Student’s t-test. Results. Both iBMMCs and aBMMCs demonstrated regulatory effects on metabolism at all stages of T2D progression; however, apoptotic BMMCs showed consistently greater efficacy. The therapeutic effect was directly associated with baseline tissue oxidative metabolism (TOM) levels at the time of administration. In early stages (adaptation at 1 month and progressive maladaptation at 3 months), when TOM levels remained relatively high, both cell types, particularly apoptotic BMMCs, produced pronounced corrective effects. In contrast, in the late stage (metabolic decompensation at 7 months), when TOM levels dropped below a critical threshold, iBMMCs, but especially aBMMCs, aggravated metabolic damage and increased animal mortality. Conclusion. Intact and apoptotic BMMCs may serve as effective adjunctive therapy in the early stages of T2D, with their therapeutic efficacy dependent on the body’s preserved stress-adaptive reserves in tissues.
A comparative study of NIH 3T3 fibroblast adhesion and proliferation on coatings of domestic and wild silk fibroin and their chitosan composites
Objective: To evaluate the in vitro cytotoxicity, adhesion, and proliferation of fibroblasts on film coatings made of Bombyx mori silk fibroin, wild silk (Tussah) fibroin, and their chitosan composites. Materials and methods. Four types of film coatings were investigated: Bombyx mori fibroin, wild silk fibroin, and their respective chitosan composites. The coatings were fabricated by casting aqueous polymer solutions followed by drying. Cytotoxicity was assessed in accordance with GOST R ISO 10993-5 using the extract assay method. NIH 3T3 fibroblast adhesion was evaluated 1 hour after seeding, while proliferation was assessed on days 1, 2, and 3 of culture. Cell quantification was performed following nuclear staining with 4′,6-diamidino-2-phenylindole (DAPI) using fluorescence microscopy combined with automated image analysis. Culture dishes containing sterile medium and medium supplemented with ethylenediaminetetraacetic acid or dimethyl sulfoxide served as control groups. Results. All tested coatings supported fibroblast viability, with metabolic activity levels comparable to those observed on standard culture plastic. Fibroblast adhesion and proliferation were consistently higher on wild silk fibroin coatings compared with Bombyx mori fibroin coatings at all time points. The incorporation of chitosan further enhanced both cell adhesion and proliferation. The most pronounced cellular response was observed on composite coatings based on wild silk fibroin and chitosan. Conclusion. Film coatings based on wild silk fibroin demonstrate an enhanced ability to support fibroblast adhesion and proliferation in vitro – more than twice as high as that of Bombyx mori fibroin with chitosan. Composite systems incorporating chitosan further enhance these properties, making them promising candidates for the development of functional biomedical coatings.
Modern materials for dermal skin substitute: principles of production and modern acellular products based on them
The treatment of extensive and deep wounds and burns remains a highly pressing issue in modern surgery. Many of the associated challenges are linked to dysfunction of the dermis – the connective tissue matrix of the skin. Without its full restoration, achieving satisfactory long-term wound healing outcomes is difficult. This review focuses on artificial acellular scaffolds for dermal regeneration, as well as the fundamental principles underlying their design. The scaffolds discussed (Integra, Giamatrix, SmartMatrix, and NovoSorb) are already widely used in clinical practice today and have demonstrated high effectiveness. Currently, most commercially available dermal substitute products, as well as tissue engineering solutions in general, are manufactured abroad. Therefore, evaluating international experience and applying it to the development of Russian-made scaffolds could significantly improve their accessibility for patients.
Prospects for allogeneic acellular tissue-engineered products in the management of post-ischemic myocardial remodeling
Advances in regenerative medicine have generated strong interest in the development of alternative treatments for heart failure and other cardiovascular diseases. Among these, gel-forming materials derived from decellularized extracellular matrices of various tissues have emerged as a promising avenue. However, reported outcomes of their effectiveness remain inconsistent, ranging from high to highly questionable. This may be due to differences in the tissues used to obtain the matrix, decellularization protocols and efficiency. This review summarizes current studies evaluating the potential of acellular injectable products derived from allogeneic biological sources to stimulate endogenous sanogenetic mechanisms in cardiac muscle regeneration.
Laboratory markers associated with tacrolimus pharmacokinetics in kidney transplant recipients
Objective: to evaluate clinical and laboratory parameters in order to identify markers that reflect the pharmaco-kinetics of tacrolimus (Tac). Materials and methods. The study included 35 kidney transplant (KT) recipients, comprising 13 women (37.1%) and 22 men (62.9%), with a median age of 48 years [37–57]. All patients received induction immunosuppressive therapy with monoclonal anti-CD25 antibodies, followed by a maintenance regimen consisting of the calcineurin inhibitor Tac in combination with antiproliferative agents (mycophenolate or azathioprine) and corticosteroids. Tac levels were measured on postoperative days 3, 7, 14, and 30. Complete blood count and biochemical parameters, including creatinine, urea, ferritin, transferrin, C-reactive protein (CRP), sodium, potassium, chloride, calcium, total protein, and total bilirubin, were assessed preoperatively and on days 1, 3, 7, 14, and 30 following KT. Results. A statistically significant positive correlation was observed between Tac trough (C₀) levels on postoperative days 3 and 7 and total bilirubin levels on day 1 (R = 0.49, p = 0.007; R = 0.48, p = 0.009, respectively). In addition, Tac C₀ level on day 3 showed a positive correlation with total bilirubin levels measured on the same day (R = 0.52, p = 0.006). Conversely, total calcium levels on day 3 were negatively correlated with Tac C₀ levels on days 7 and 14 (R = –0.60, p = 0.031; R = –0.56, p = 0.046, respectively). Conclusion. Total bilirubin levels on postoperative day 1 are directly associated with Tac levels on days 3 and 7 following KT. Additionally, lower total calcium levels on day 3 are associated with higher Tac concentrations on days 7 and 14.
The effect of CYP3A5 gene polymorphism on the pharmacokinetics of tacrolimus in heart transplant recipients
Objective: to assess the association between CYP3A5 isoenzyme genotypes and tacrolimus (Tac) dose and whole-blood levels in heart transplant (HT) recipients in the early and long-term post-transplant periods. Materials and methods. The study included 189 HT recipients receiving Tac as part of their maintenance immunosuppressive therapy. CYP3A5 polymorphisms (*1/*1, *1/*3, *3/*3) were determined via real-time polymerase chain reaction. Tac dose and whole-blood concentrations were evaluated at 1 month, 1 year, and at long-term follow-up (>1 year; mean 7.0 ± 3.1 years) after HT. In addition, general and biochemical blood test results were analyzed. Results. The CYP3A5 *3/*3 genotype was predominant among HT recipients (89%), while the *1/*3 genotype was identified in 10% and the *1/*1 genotype in 1% of patients. Carriers of the *1 allele (*1/*3 and *1/*1) required substantially higher Tac doses – approximately twofold or greater – compared with *3/*3 carriers at all follow-up time points: at 1 month post-transplant, median doses were 8.0 [6.0–10.25] mg and 11.0 [9.5–12.5] mg versus 4.0 [3.0–6.0] mg (p < 0.001); at 1 year, 8.0 [6.0–9.0] mg and 10.0 [9.0–11.0] mg versus 3.0 [2.0–5.0] mg (p < 0.001); and at long-term follow-up, 7.0 [6.0–8.0] mg and 9.0 [7.5–10.5] mg versus 3.0 [2.0–5.0] mg (p < 0.001). Tac whole-blood levels did not differ significantly between groups of heart recipients at any time point during follow-up. However, the concentration-to-dose ratio (C0/D) was significantly higher in *3/*3 carriers across all follow-up periods (p = 0.000). At long-term follow-up, patients with the *3/*3 genotype exhibited significantly higher median serum creatinine levels compared with carriers of the *1 allele (107.6 [87.3–142.1] μmol/L vs 90.2 [75.0–99.7] μmol/L; p = 0.001). Correlation analysis revealed significant associations between Tac levels and white blood cell count (r = 0.148; p = 0.027), total bilirubin levels (r = 0.217; p < 0.001), and cholesterol levels (r = –0.274; p < 0.001). Conclusion. The non-expressing CYP3A5 *3/*3 genotype is predominant among HT recipients (89%). Carriers of the functional CYP3A5 *1 allele (*1/*3 and *1/*1) require twofold or higher Tac doses to achieve target whole-blood levels compared with *3/*3 carriers. These findings confirm that CYP3A5 polymorphism is a major determinant of interindividual variability in Tac pharmacokinetics in HT recipients. Pre-treatment pharmacogenetic testing for CYP3A5 may facilitate individualized dosing strategies, enabling more rapid attainment of therapeutic drug levels.
Hemodynamic activation of von Willebrand factor: an experimental study for predicting thrombus formation in blood-contacting medical devices
Objective: to evaluate the effect of hemodynamic stress on the functional activity of von Willebrand factor (VWF) in vitro and to assess the potential of these data for predicting thrombus formation during testing of blood-contacting medical devices. Materials and methods. Fresh human platelet-rich plasma (PRP) was used in all experiments. Hemodynamic conditions mimicking vascular stenosis were simulated in a closed-loop system equipped with a peristaltic pump using a narrow channel (diameter 0.7 mm), generating shear rates (γ) of 1000, 3000, and 5000 s–1. Control experiments were performed under low-shear conditions in a wider channel (diameter 3 mm). von Willebrand factor activity (vWF Act, %) was measured after one and two circulation cycles. Results. Under control conditions, the reduction in VWF activity was minimal, decreasing to 69.2% after two circulation cycles. In stenosis-like channels, a pronounced decrease in VWF activity was observed, with the magnitude depending on shear rate: 65.1% at γ = 1000 s–1, 63.6% at γ = 3000 s–1, and 62.6% at γ = 5000 s–1. The most substantial decline occurred after the first passage through the stenotic segment. At the highest shear rate (γ = 5000 s–1), microscopic analysis revealed the formation of platelet aggregates. Conclusion. The study demonstrates that increasing shear rate leads to enhanced activation and proteolytic degradation of VWF, primarily due to the loss of high-molecular-weight multimers. These findings highlight the critical role of hydrodynamic conditions in the development of hemostatic disturbances associated with vascular stenoses and mechanical circulatory support systems. Incorporating the assessment of VWF activity and multimer distribution into testing protocols for vascular prostheses and extracorporeal devices may improve prediction of their hemocompatibility.
Experimental evaluation of allogeneic and xenogeneic biomaterials for regeneration of circular intestinal defects
Objective: to investigate the regenerative potential of allogeneic and xenogeneic biomaterials in the repair of circular bowel defects. Materials and methods. The study was conducted on sexually mature male Wistar rats (1 year old, weighing ~300 g; n = 98). In the experimental group (n = 49), allogeneic decellularized biomaterial (ADB) derived from rat bowel was implanted. In the control group (n = 49), xenogeneic biomaterial derived from the fibrous capsule of a human cadaveric kidney was used. In both groups, a 30-mm segment of the ileum was resected, and the biomaterials were implanted at the defect site as end-to-end tubular grafts of similar dimensions. The implanted biomaterials were subsequently subjected to decellularization and morphological analysis. Results. In the experimental group, 2–3 months after transplantation of ADB, the full architectural structure of the small bowel wall was restored. The implanted biomaterial was completely resorbed and replaced by an organ-specific regenerate, with confirmed presence of blood vessels, nerve fibers, and Peyer’s patches. In the control group, transplantation of xenogeneic biomaterial resulted in 100% mortality within the early postoperative period (7–14 days), associated with graft rejection and a pronounced immune-inflammatory response in the abdominal cavity. Conclusion. The proposed approach promotes regeneration of continuous small bowel segments measuring 30 mm or more and enables restoration of all structural components of the bowel wall. This method shows potential for the treatment of conditions such as short bowel syndrome, inflammatory-destructive bowel diseases, and for the closure of circular defects following bowel resection.
Evolution of models in urological surgery and transplantology: from laboratory animals to artificial intelligence
Background. Animal experiments play a vital role in modern surgery, enabling the development of new surgical techniques, transplant materials, and more. In addition, modern surgery and transplant medicine utilize robotic systems and artificial intelligence to minimize intraoperative blood loss and wound infections, facilitate donor– recipient matching, and predict graft survival. Objective: to analyze the evolution of in vivo surgical models and evaluate modern strategies for transplantation and explantation. Materials and methods. A literature search was conducted in the SCOPUS, PubMed, and the Russian Science Citation Index (RSCI) databases using the following search terms: «хирургические модели на животных» (meaning «animal surgical models» in English), «трансплантация почки» (kidney transplantation), «ксенотрансплантация» (xenotransplantation), «искусственный интеллект в трансплантологии и хирургии» (artificial intelligence in transplantology and surgery) and «роботизированная хирургия» (robot-assisted surgery). A total of 430 publications from Russian and international journals published between 2006 and 2025 were analyzed. Following the selection process, 87 publications were included in the review. The evolution from anatomical studies to complex surgical systems was traced, with a key milestone being the introduction of kidney transplantation models in large animals (pigs). The current stage is characterized by integration of robotic systems and artificial intelligence, ensuring minimal invasiveness and high precision. Conclusion. Testing on laboratory animals remains essential, particularly for surgical procedures that cannot be adequately modeled mathematically.
Vascular calcification progression after parathyroidectomy in patients on renal replacement therapy: a pilot study
Objective: to evaluate the progression of vascular calcification in dialysis-dependent patients following parathyroidectomy (PTX) for secondary hyperparathyroidism (SHPT) over long-term follow-up. Materials and methods. This prospective cohort study included 63 adult patients with stage 5 chronic kidney disease receiving renal replacement therapy. The main group (n = 55) underwent successful PTX for SHPT, while the control group (n = 8) received medical therapy. Cardiac computed tomography was performed to assess the coronary artery calcification (CAC) index, and lateral abdominal radiography was used for semi-quantitative assessment of abdominal aortic calcification (AAC). Assessments were conducted at baseline and after 18 months of follow-up. Results. The primary analysis included 44 patients in the PTX group and 6 in the control group who completed follow-up. The mean change in CAC was +452 (95% CI: –223 to 891; p = 0.101) in the PTX group and +1432 (95% CI: –772 to 2778; p = 0.065) in controls, with no significant between-group difference (Δ = –980; 95% CI: –2631 to 1542; p = 0.434). For AAC, the mean change was 0 points (95% CI: –1 to 1; p = 0.775) in the PTX group and +3 points (95% CI: –0.2 to 5.8; p = 0.038) in controls; the between-group difference approached significance (Δ = –2.9; 95% CI: –6.3 to 0.54; p = 0.098). Following PTX, serum calcium and phosphate levels decreased by 0.13 (0.29) mmol/L (p = 0.003) and 0.25 (0.64) mmol/L (p = 0.013), respectively, while remaining unchanged in the control group (effect sizes: 0.52 SD and 0.31 SD). Achieving target parathyroid hormone (PTH <15 pmol/L), along with normalized calcium and phosphate levels and statin therapy, was linked to an 85% reduction in the risk of calcification progression (95% CI: –98% to –0.01%; p = 0.050; R2 = 0.400). Conclusions. Differences in vascular calcification progression did not reach statistical significance for the primary endpoint, likely due to the small control group and heterogeneity of effects. However, significant progression of AAC was observed in the control group but not in the PTX group. These findings suggest potential clinical relevance, although results should be interpreted only in the context of clinical significance and can be used in future studies.
Development of the kidney transplant program in Uzbekistan: a multi-year analysis of surgical activity and future perspectives
Over the past two decades, kidney transplantation (KT) in Uzbekistan has developed unevenly, passing through several stages of growth. Objective: to evaluate these developments by analyzing changes in the volume of transplant procedures, their geographic distribution, and the organization of post-transplant patient follow-up. Materials and methods. The study included 2,803 patients who underwent KT between 2007 and July 2025. Data were obtained from the national registry of recipients of immunosuppressive therapy, as well as from medical institutions at various levels of care. The analysis focused on annual transplant rates, geographic distribution of surgeries, the contribution of individual transplant centers, and the regional distribution of patients during the rehabilitation period. Results. An increase in surgical activity in Uzbekistan became evident only after 2017, with the most pronounced growth in the number of KT procedures observed between 2021 and 2024. During this period, KT transitioned from a rare, high-tech procedure to a routine clinical intervention performed primarily at national transplant centers. The majority of transplantations were carried out at Republican Specialized Scientific and Practical Medical Center of Surgery. At the same time, significant regional disparities were identified: most patients continue to receive care in the capital city, while the involvement of regional healthcare institutions remains limited but gradually increasing. Conclusion. The findings indicate the formation of a stable national KT program in Uzbekistan; however, the system of post-transplant follow-up across regions remains inconsistent. Strengthening the capacity of regional and district healthcare facilities, expanding telemedicine services, and enhancing personnel training may improve access to specialized care and reduce the workload on central transplant centers.
Congratulations on Anniversary Vyacheslav Leonidovich Korobka
8 апреля 2026 года свой 60-летний юбилей отметил Вячеслав Леонидович Коробка, доктор медицинских наук, профессор, главный врач ГБУ РО «Ростовская областная клиническая больница», заведующий кафедрой реконструктивной, пластической, торакальной, сердечно-сосудистой хирургии и трансплантологии ФГБОУ ВО «РостГМУ» Минздрава России, главный внештатный специалист по хирургии и трансплантологии Министерства здравоохранения Ростовской области.