Dalibor Nikolic
@iit.kg.ac.rs
Department of Technical-Technological Sciences
Institute for Information technologies Kragujevac
RESEARCH, TEACHING, or OTHER INTERESTS
Computer Graphics and Computer-Aided Design, Mechanical Engineering, Bioengineering, Computer Engineering
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Amra Ramović Hamzagić, Danijela Cvetković, Marina Gazdić Janković, Nevena Milivojević Dimitrijević, Dalibor Nikolić, Marko Živanović, Nikolina Kastratović, Ivica Petrović, Sandra Nikolić, Milena Jovanović,et al.
MDPI AG
(1) Background: Cancer stem cells (CSCs) are a subpopulation of cells in a tumor that can self-regenerate and produce different types of cells with the ability to initiate tumor growth and dissemination. Chemotherapy resistance, caused by numerous mechanisms by which tumor tissue manages to overcome the effects of drugs, remains the main problem in cancer treatment. The identification of markers on the cell surface specific to CSCs is important for understanding this phenomenon. (2) Methods: The expression of markers CD24, CD44, ALDH1, and ABCG2 was analyzed on the surface of CSCs in two cancer cell lines, MDA-MB-231 and HCT-116, after treatment with 5-fluorouracil (5-FU) using flow cytometry analysis. A machine learning model (ML)–genetic algorithm (GA) was used for the in silico simulation of drug resistance. (3) Results: As evaluated through the use of flow cytometry, the percentage of CD24-CD44+ MDA-MB-231 and CD44, ALDH1 and ABCG2 HCT-116 in a group treated with 5-FU was significantly increased compared to untreated cells. The CSC population was enriched after treatment with chemotherapy, suggesting that these cells have enhanced drug resistance mechanisms. (4) Conclusions: Each individual GA prediction model achieved high accuracy in estimating the expression rate of CSC markers on cancer cells treated with 5-FU. Artificial intelligence can be used as a powerful tool for predicting drug resistance.
Katarina Virijević, Marko N. Živanović, Dalibor Nikolić, Nevena Milivojević, Jelena Pavić, Ivana Morić, Lidija Šenerović, Luka Dragačević, Philipp J. Thurner, Manuel Rufin,et al.
American Chemical Society (ACS)
Here, an artificial intelligence (AI)-based approach was employed to optimize the production of electrospun scaffolds for in vivo wound healing applications. By combining polycaprolactone (PCL) and poly(ethylene glycol) (PEG) in various concentration ratios, dissolved in chloroform (CHCl3) and dimethylformamide (DMF), 125 different polymer combinations were created. From these polymer combinations, electrospun nanofiber meshes were produced and characterized structurally and mechanically via microscopic techniques, including chemical composition and fiber diameter determination. Subsequently, these data were used to train a neural network, creating an AI model to predict the optimal scaffold production solution. Guided by the predictions and experimental outcomes of the AI model, the most promising scaffold for further in vitro analyses was identified. Moreover, we enriched this selected polymer combination by incorporating antibiotics, aiming to develop electrospun nanofiber scaffolds tailored for in vivo wound healing applications. Our study underscores three noteworthy conclusions: (i) the application of AI is pivotal in the fields of material and biomedical sciences, (ii) our methodology provides an effective blueprint for the initial screening of biomedical materials, and (iii) electrospun PCL/PEG antibiotic-bearing scaffolds exhibit outstanding results in promoting neoangiogenesis and facilitating in vivo wound treatment.
Dragan Sekulic, Aleksandar Tomic, Andreja Dimic, Aleksandar Mitrovic, Lazar Davidovic, Dragana Paunovic, Dalibor Nikolic, Uros Miladinovic, Igor Sekulic, Nemanja Rancic,et al.
National Library of Serbia
Background/Aim. The best treatment for the occlusion of the largest artery in the thigh is a femorodistal (FD) bypass. Ankle-brachial index (ABI) and multidetector computed tomographic (MDCT) angiography are the gold standards for diagnosing peripheral arterial occlusive disease. The finite element analysis (FEA) method can help measure the quantity of blood flow and arterial pressure in the arteries in the leg. The aim of this study was to examine the possibility of using the FEA method in predicting the outcome of FD bypass surgery. Methods. The study involved 45 patients indicated for FD arterial reconstruction from December 1, 2021, to March 31, 2023. Each patient underwent pre- and postoperative MDCT angiography of the arteries of the lower extremities, on the basis of which, with the use of FEA, models were made for measuring ABI. All patients had their ABI measured pre-operatively and postoperatively using the Doppler ultrasound and sphygmomanometer. Based on the findings of the preoperative MDCT angiography, postoperative virtual surgical models were created using the FEA method, on which ABI were also measured. The values of ABI were divided into five groups: ABI measured preoperatively (ABI pre-op), ABI measured postoperatively (ABI post-op), ABI measured on FEA models based on the MDCT findings [ABI (sim) pre-op], ABI sim post-op, and ABI measured on virtual surgery model [ABI sim post-op (virtual)]. The ABI of the models were statistically compared with preoperative and postoperative measurements done on patients. Results. The values based on the virtual ABI model did not show significant differences compared to the values obtained on patients and values obtained with the FEA method using MDCT angiography (p < 0.001). A strong statistically significant correlation was shown between the virtual ABI and the values obtained by the other two methods, measured on the postoperative MDCT angiography model and virtual postoperative model (p < 0.001). Conclusion. Virtual simulation based on the MDCT angiography parameters of peripheral blood vessels can be successfully used to predict the immediate outcome of the FD bypass surgery.
I. Koncar, D. Nikolic, Z. Milosevic, N. Bogavac-Stanojevic, N. Ilic, M. Dragas, M. Sladojevic, M. Markovic, A. Vujcic, N. Filipovic,et al.
Frontiers Media SA
ObjectivesThe study aimed to identify differences and compare anatomical and biomechanical features between elective and ruptured abdominal aortic aneurysms (AAAs).MethodsData (clinical, anatomical, and biomechanical) of 98 patients with AAA, 75 (76.53%) asymptomatic (Group aAAA) and 23 (23.46%) ruptured AAA (Group rAAA), were prospectively collected and analyzed. Anatomical, morphological, and biomechanical imaging markers like peak wall stress (PWS) and rupture risk equivalent diameter (RRED), comorbid conditions, and demographics were compared between the groups. Biomechanical features were assessed by analysis of Digital Imaging and Communication in Medicine images by A4clinics (Vascops), and anatomical features were assessed by 3Surgery (Trimensio). Binary and multiple logistic regression analysis were used and adjusted for confounders. Accuracy was assessed using receiving operative characteristic (ROC) curve analysis.ResultsIn a multivariable model, including gender and age as confounder variables, maximal aneurysm diameter [MAD, odds ratio (OR) = 1.063], relative intraluminal thrombus (rILT, OR = 1.039), and total aneurysm volume (TAV, OR = 1.006) continued to be significant predictors of AAA rupture with PWS (OR = 1.010) and RRED (OR = 1.031). Area under the ROC curve values and correct classification (cc) for the same parameters and the model that combines MAD, TAV, and rILT were measured: MAD (0.790, cc = 75%), PWS (0.713, cc = 73%), RRED (0.717, cc = 55%), TAV (0.756, cc = 79%), rILT (0.656, cc = 60%), and MAD + TAV + rILT (0.797, cc = 82%).ConclusionBased on our results, in addition to MAD, other important predictors of rupture that might be used during aneurysm surveillance are TAV and rILT. Biomechanical parameters (PWS, RRED) as valuable predictors should be assessed in prospective clinical trials. Similar studies on AAA smaller than 55 mm in diameter, even difficult to organize, would be of even greater clinical value.
Katarina Virijević, Bojana Marković, Jelena Grujić, Milena Jovanović, Nikolina Kastratović, Marko Živanović, Dalibor Nikolić, and Nenad Filipović
MDPI
Dalibor D. Nikolic and Nenad Filipovic
Elsevier
Miljan Milosevic, Milos Anic, Dalibor Nikolic, Bogdan Milicevic, Milos Kojic, and Nenad Filipovic
Hindawi Limited
Stents made by different manufacturers must meet the requirements of standard in vitro mechanical tests performed under different physiological conditions in order to be validated. In addition to in vitro research, there is a need for in silico numerical simulations that can help during the stent prototyping phase. In silico simulations have the ability to give the same stent responses as well as the potential to reduce costs and time needed to carry out experimental tests. The goal of this paper is to show the achievements of the computational platform created as a result of the EU-funded project InSilc, used for numerical testing of most standard tests for validation of preproduction bioresorbable vascular scaffolds (BVSs). Within the platform, an ad hoc simulation protocol has been developed based on the finite element (FE) analysis program PAK and user interface software CAD Field and Solid. Two different designs of two different stents have been numerically simulated using this integrated tool, and the results have been demonstrated. The following standard tests have been performed: longitudinal tensile strength, local compression, kinking, and flex 1-3. Strut thickness and additional pocket holes (slots) in two different scaffolds have been used as representative parameters for comparing the mechanical characteristics of the stents (AB-BVS vs. AB-BVS-thinner and PLLA-prot vs. PLLA-plot-slot). The AB-BVS-thinner prototype shows better overall stress distribution than the AB-BVS, while the PLLA-prot shows better overall stress distribution in comparison to the PLLA-plot-slot. In all cases, the values of the maximum effective stresses are below 220 MPa—the value obtained by in vitro experiment. Despite the presented results, additional considerations should be included before the proposed software can be used as a validation tool for stent prototyping.
Danko Z. Milasinovic, Dragan B. Sekulic, Dalibor D. Nikolic, Arso M. Vukicevic, Aleksandar P. Tomic, Uros M. Miladinovic, Dragana S. Paunovic, and Nenad D. Filipovic
Elsevier BV
Nenad Filipovic, Dalibor Nikolic, Velibor Isailovic, Miljan Milosevic, Vladimir Geroski, Georgia Karanasiou, Martin Fawdry, Aiden Flanagan, Dimitrios Fotiadis, and Milos Kojic
Elsevier BV
Miljan Milosevic, Milos Anic, Dalibor Nikolic, Vladimir Geroski, Bogdan Milicevic, Milos Kojic, and Nenad Filipovic
Frontiers Media SA
Bioresorbable vascular scaffolds (BVS), made either from polymers or from metals, are promising materials for treating coronary artery disease through the processes of percutaneous transluminal coronary angioplasty. Despite the opinion that bioresorbable polymers are more promising for coronary stents, their long-term advantages over metallic alloys have not yet been demonstrated. The development of new polymer-based BVS or optimization of the existing ones requires engineers to perform many very expensive mechanical tests to identify optimal structural geometry and material characteristics. in silico mechanical testing opens the possibility for a fast and low-cost process of analysis of all the mechanical characteristics and also provides the possibility to compare two or more competing designs. In this study, we used a recently introduced material model of poly-l-lactic acid (PLLA) fully bioresorbable vascular scaffold and recently empowered numerical InSilc platform to perform in silico mechanicals tests of two different stent designs with different material and geometrical characteristics. The result of inflation, radial compression, three-point bending, and two-plate crush tests shows that numerical procedures with true experimental constitutive relationships could provide reliable conclusions and a significant contribution to the optimization and design of bioresorbable polymer-based stents.
Dalibor D. Nikolic and Nenad D. Filipovic
Wiley
Aleksandar Cvetković, Danijela Cvetković, Danko Milašinović, Nemanja Jovičić, Nikola Miailović, Dalibor Nikolić, Slobodanka Mitrović, and Nenad Filipović
Faculty of Engineering, University of Kragujevac
This is a feasibility study for the application of a novel concept of single-needle device for localized chemotherapy. Systemic chemotherapy has numerous and severe side effects. To conduct localized (electro)chemotherapy, we designed a novel device that does not currently exist on the market. Electrochemotherapy is based on the cell membranes temporary or permanent permeabilization using an electric current of defined characteristics. Electroporation can be reversible, when after a period of opened pores and membrane permeability increasing, membranes and cells return to their original state without damage. Electroporation can be an irreversible process when the pores on the membrane remain permanently open, electrolyte imbalance occurs resulting in cell death. Electrochemotherapy involves a combination of cytostatics and reversible electroporation, when pores on the cell membrane are temporarily opened and, during that short period, a large amount of cytostatic is entered into the cell, which is a macromolecule that would not normally penetrate the cell. After closing the pores, the cytostatic remains trapped in the cell in large quantities, multiplying its effect. In this paper, we present a feasibility study of electroporation application in irreversible mode without the use of cytostatics. Fresh porcine liver tissue was used to show that the constructed equipment was effective, thus opening the way for further investigations using reversible electroporation with the application of cytostatics, which would represent localized electrochemotherapy. We penetrated the virtual tumor area (liver metastases) with a specially designed needle with electrodes that generate an electric field and apply electroporation in the target tissue. We have shown that the constructed novel design single needle equipment for electroporation is effective on the experimental model of isolated porcine liver. Further steps in our study will be the testing of electrochemotherapy in an experimental animal model in vivo.
Dragan Sekulić, Aleksandar Tomić, Danko Milašinović, Dalibor Nikolić, Dragana Paunović, Uroš Miladinović, Igor Sekulić, Maja Savić-Sekulić, and Boško Milev
Centre for Evaluation in Education and Science (CEON/CEES)
Objective. Femoropopliteal bypass is indicated in the advanced stage of peripheral arterial occlusive disease. The indications for surgical treatment are determined on the basis of a clinical exam, "ankle-brachial index" and angiographic findings. Using the finite element analysis method, three-dimensional models can be made based on angiography, and these models can be used to measure different physical quantities and calculate the value of the "ankle-brachial index". The aim of this paper is to show the hemodynamics of arteries by using the finite element analysis method based on preoperative and postoperative angiography, as well as physical quantities that can be measured in this way. Methods. This case shows the hemodynamics of femoropopliteal bypass in the preoperative and postoperative models. The models obtained by finite element analysis show: pressure, shear stress, velocities, and streamlines. The pressure, i.e. the "ankle-brachial index", was compared with the values measured on the patient, while the other three values were compared preoperatively and postoperatively. Results. Postoperatively, higher values of pressure and "ankle-brachial index" were measured on the patient and on the models. Wall shear stress and velocity values were reduced in postoperative models. The streamlines showed a dominant anterior tibial artery. Conclusion. The values of physical quantities measured on patient and on the models obtained by the finite element analysis method correlate significantly. Some physical quantities could indicate the "weak points" of a particular model.
Dalibor D. Nikolic, Dragan B. Sekulic, Danko Z. Milasinovic, Dragana S. Paunovic, Igor M. SekuliC, Igor B. Saveljic, and Nenad D. Filipovic
IEEE
Femoro-popliteal “by-pass” is indicated in the advanced stage of peripheral arterial occlusive disease. Indications for surgical treatment are set on the basis of the clinical picture, “ankle-brachial index” and angiographic findings. By the method of finite element analysis, three-dimensional models can be made on the basis of scanning angiography, on which we can measure different physical quantities and calculate the value of the “ankle-brachial index”. The aim is to show the hemodynamics of arteries by the method of finite element analysis (FEA) based on preoperative and postoperative scan angiography as well as physical quantities that can be measured in this way. In this review, the hemodynamics of femoro-popliteal “by-pass” on the preoperative and postoperative model are presented. The models obtained by FEA show: pressure, shear stress, velocities, and streamlines. Pressure, “ankle-brachial index”, compared with the values measured on the patient, with FEA results preoperatively and postoperatively. Postoperatively, higher values of pressure and “ankle-brachial index” were measured on the patient and on the models. The values shown in the models are significantly correlated with the values measured on the patient. Shear stress and velocity values are significantly reduced on postoperative models. The streamlines show a dominant anterior tibial artery. The values of physical quantities measured on the patient and on the models obtained by the FEA method correlate to a significant extent.
Igor Saveljic, Tijana Djukic, Dalibor Nikolic, Smiljana Djorovic, and Nenad Filipovic
IEEE
Cardiovascular diseases are the leading cause of death in the world with an incidence of about 30% of total mortality. It is a disease of the blood vessels of the heart that most often occurs due to the process of atherosclerosis. The process of atherosclerosis leads to narrowing of the coronary arteries, and thus to a reduced supply of blood or oxygen to the heart muscle. A fractional flow reserve (FFR) indicates the severity of blood flow blockages in the coronary arteries and allows physicians to identify which specific lesion or lesions are responsible for patient ischemia. In this paper, we studied the values of the FFR, using numerical simulations, on the geometries obtained by reconstructing the angiogram images.
Katarina Virijević, Jelena Grujić, Mihajlo Kokanović, Dalibor Nikolić, Marko Živanović, and Nenad Filipović
Springer International Publishing
Nevena Milivojević, Dalibor Nikolić, Dragana Šeklić, Živana Jovanović, Marko Živanović, and Nenad Filipović
Springer International Publishing
Dalibor Nikolić, Igor Saveljić, and Nenad Filipović
Springer International Publishing
Igor Saveljic, Dalibor Nikolic, Zarko Milosevic, and Nenad Filipovic
Springer International Publishing
Maja Milosevic, Nikola Mijailovic, Dalibor Nikolic, Nenad Filipovic, Aleksandar Peulic, Mirko Rosic, and Suzana Pantovic
Centre for Evaluation in Education and Science (CEON/CEES)
Abstract Blood vessels diseases such as cardiac infarction with coronary artery occlusion, peripheral arterial disorders, or stroke of carotid or cerebral arteries, are the leading causes of death in the world. One of medical procedures for clinical treatment of vascular diseases is the blood vessels grafting. As the autologous blood vessels, which are the “golden standard” for coronary grafting, are not always suitable for blood vessels grafting, there is a need to develop artificial blood vessels as a vascular prostheses, either from natural and synthetic materials, permanent synthetic or biodegradable scaffolds which would be suitable for vascular grafts. Considering this to be our study goal we made bilayered biodegradable polycaprolactone scaffolds with different properties and evaluated their morphological and biomechanical characteristics.
Zarko Milosevic, Igor Saveljic, Dalibor Nikolic, Nebojsa Zdravkovic, Nenad Filipovic, and Neda Vidanovic
European Alliance for Innovation n.o.
Benign Paroxysmal Positional Vertigo (BPPV) is the most common vestibular disorder. In this paper we tried to investigate a model of the semi-circular canal (SCC) with parametrically defined dimension and full 3D three SCC from patient-specific 3D reconstruction. Full Navier-Stokes equations and continuity equations are used for fluid domain with Arbitrary-Lagrangian Eulerian (ALE) formulation for mesh motion. Fluid-structure interaction for fluid coupling with cupula deformation is used. Particle tracking algorithm has been used for particle motion. Velocity distribution, shear stress and force from endolymph side are presented for one parametric SCC and three patient-specific SCC. All models are used for correlation with the same experimental protocols with head moving and nystagmus
Bojana Andjelkovic Cirkovic, Velibor Isailovic, Dalibor Nikolic, Igor Saveljic, Oberdan Parodi, and Nenad Filipovic
Springer International Publishing
Nebojsa Zdravkovic, Zarko Milosevic, Igor Saveljic, Dalibor Nikolic, Vladimir Miloradovic and N. Filipović
Mechanical Engineering Faculty in Slavonski Brod
Igor B. Koncar, Dalibor Nikolic, Zarko Milosevic, Nikola Ilic, Marko Dragas, Milos Sladojevic, Miroslav Markovic, Nenad Filipovic, and Lazar Davidovic
Elsevier BV
Nenad Filipovic, Zarko Milosevic, Igor Saveljic, Dalibor Nikolic, and Milos Radovic
Springer International Publishing