Jelena Najdanovic - Academia.edu (original) (raw)

Papers by Jelena Najdanovic

Универзитет у Београду, Aug 3, 2016

Contemporary materials, Jun 27, 2023

Regenerative medicine (RM) exploits the innate potential of the human body to effectively repair ... more Regenerative medicine (RM) exploits the innate potential of the human body to effectively repair and regenerate damaged tissues and organs with the help of various biomaterials. Tissue engineering (TE) makes it possible to replace damaged tissues and organs with new ones. Research in the field of biomaterials has significantly improved the area of RM and TE. Biomaterials are used as orthopedic, dental, cardiovascular implants, medical devices, in the fields of reconstructive and regenerative medicine, among others. Important preconditions for the biomaterial to be used for implantation are its biocompatibility and biofunctionality. Biomaterials should enable adhesion, migration, proliferation and differentiation of cells. The biological properties of biomaterials are a reflection of their physicochemical properties, such as internal architecture, surface characteristics and charge. Biomaterials used in tissue regeneration should mimic the natural structure of the extracellular matrix and represent a physiological microenvironment for normal cellular functions. These biomaterials should also have adequate biodegradability properties to facilitate the formation and growth of new tissue. Biomaterials for use in RM can be of natural or synthetic origin, polymers by structural properties, ceramic and composite type, and based on bioreactivity they can be bioinert or bioactive. In RM and TE, polymers of different classes, natural and synthetic, are used, which can be made as intelligent materials. The structure of hydrogels in the form of a porous network represents a good matrix for cell activity. Ceramic biomaterials based on hydroxyapatite (HAp) are selected for use in RM and TE, especially solid tissues. Properties, such as composition, particle size, material shape, porosity, surface charge, topography, etc., are relevant for the proper use of HAp materials. The properties of HAp allow modification of its structure, surface, particle size design at the micro and nano level, hybridization with polymers, metals, etc. which is very important for its applications. Designed micro-nanohybrid HAp structure is most similar to the bone structure, making the cell environment closest to natural. Bone tissue engineering (BTE) is based on the combined use of cells, osteostimulating (osteoinductive) factors and biomaterials as a scaffolds and carriers for bone regeneration and defects repair. In BTE adipose-derived mesenchymal stem cells (ADSCs) are often used that are induced in vitro towards osteogenic cells or endothelial cells, and freshly isolated stromal vascular fraction can also be used. Blood components (PRP, blood plasma or blood clot) can be included in the composition of the BTE construct as a source of osteoinductive factors. In vitro models and methods were used to examine the biocompatibility, immunomodulatory and regenerative potential of biomaterials, as well as their influence on cellular functions. After in vitro methods, and before clinical studies, various in vivo animal models are used to examine the regenerative potential of biomaterials, such as subcutaneous implantations and bone defects in tibia, femur and calvaria in experimental animals (mouse, rat, rabbit).

PubMed, 2014

The anti-proliferative activitiy of Hypogymnia physodes methanol extracts (ME) and its main const... more The anti-proliferative activitiy of Hypogymnia physodes methanol extracts (ME) and its main constituents, physodalic acid (P1), physodic acid (P2), and 3-hydroxy physodic acid (P3), was tested on human cancer HeLa cell lines. Three lichen depsidones, P1, P2 and P3, were isolated from H. physodes ME using column chromatography and their structures were determined by UV, ESI TOF MS, 1H and 13C NMR. The content of P1, P2 and P3 in ME was determined using reversed-phase highperformance liquid chromatography with photodiode array detection. P1-3 represented even 70 % of the studied extract. The HeLa cells were incubated during 24 and 72 h in the presence of ME and depsidones P1, P2 and P3, at concentrations of 10-1000 μg/ml. Compounds P2 and P3 showed higher activity than compound P1. Half maximal inhibitory concentrations (IC50, μg/ml) of P1, P2, P3 and ME for 24-h incubation were 964, 171, 97 and 254 μg/ml, respectively, while for 72-h incubation they were 283, 66, 63 and 68 μg/ml. As far as we know, this is the first report on the effect of H. physodes ME and their depsidones on HeLa cells.

Acta Medica Medianae, Dec 15, 2021

Honey has long been recognized as a special natural product, not only because of its nutritional ... more Honey has long been recognized as a special natural product, not only because of its nutritional value, but also because of its healing properties. Although it is mostly composed of carbohydrates, it also contains numerous enzymes, amino acids, organic acids, polyphenols, minerals, vitamins and other substances, whose presence varies depending on the type of honey and its botanical and geographical origin. Thanks to its antimicrobial properties, as well as its beneficial effect on wound healing, tissue repair and regeneration, honey could have a potential role in the fields of tissue engineering and regenerative medicine.

Hrana i ishrana, 2021

Stojanovic et al.: In vitro analysis of the biological activity of royal jelly on different...

Biotechnology & Biotechnological Equipment, Aug 2, 2016

Vascular development has a great significance in the osteogenic process and in bone tissue engine... more Vascular development has a great significance in the osteogenic process and in bone tissue engineering (BTE). BTE is based on various combinations of three principal types of components: biomaterials as scaffolds, regulatory signals and cells. The aim of our study was to evaluate, at gene expression and histological level, the effect of BTE triad components on the vascularization process in an ectopic bone-forming model in mice. Bone mineral matrix (BMM) was used as a scaffold and a carrier, platelet-rich plasma (PRP) as a source of regulatory signals and adipose stem cells (ASCs) as a source of cells for endothelial differentiation, in order to show how and to what extent the biological enrichment of BMM influences the outcome of the osteogenic process and its key precondition, vascularization. Implants composed of BMM, PRP and ASCs in vitro induced into endothelial cells (EPB implants) and implants composed of BMM and PRP (PB implants) were compared with implants composed of BMM only (B implants). More pronounced endothelialrelated gene expression and stronger VCAM-1 (vascular cell adhesion molecule-1) immunoexpression were observed in EPB implants in comparison with PB and B ones at later time points of the in vivo experimental period. Osteopontin gene expression and immunoexpression of osteopontin were significantly higher in EPB compared to PB and B implants. Therefore, addition of ASCs combined with PRP to BMM improved the vascularization process in the ectopic boneforming model, which makes this BTE composition the most favourable among the examined types of implants for application in BTE.

World Journal of Stem Cells, 2021

BACKGROUND A major problem in the healing of bone defects is insufficient or absent blood supply ... more BACKGROUND A major problem in the healing of bone defects is insufficient or absent blood supply within the defect. To overcome this challenging problem, a plethora of approaches within bone tissue engineering have been developed recently. Bearing in mind that the interplay of various diffusible factors released by endothelial cells (ECs) and osteoblasts (OBs) have a pivotal role in bone growth and regeneration and that adjacent ECs and OBs also communicate directly through gap junctions, we set the focus on the simultaneous application of these cell types together with platelet-rich plasma (PRP) as a growth factor reservoir within ectopic bone tissue engineering constructs. AIM To vascularize and examine osteogenesis in bone tissue engineering constructs enriched with PRP and adipose-derived stem cells (ASCs) induced into ECs and OBs. METHODS ASCs isolated from adipose tissue, induced in vitro into ECs, OBs or just expanded were used for implant construction as followed: BPEO, endothelial and osteogenic differentiated ASCs with PRP and bone mineral matrix; BPUI, uninduced ASCs with PRP and bone mineral matrix; BC (control), only bone mineral matrix. At 1, 2, 4 and 8 wk after subcutaneous implantation in mice, implants were extracted and endothelial-related and bone-related gene expression were analyzed, while histological analyses were performed after 2 and 8 wk. RESULTS The percentage of vascularization was significantly higher in BC compared to BPUI and BPEO constructs 2 and 8 wk after implantation. BC had the lowest endothelial-related gene expression, weaker osteocalcin immunoexpression and Spp1 expression compared to BPUI and BPEO. Endothelial-related gene expression and osteocalcin immunoexpression were higher in BPUI compared to BC and BPEO. BPEO had a higher percentage of vascularization compared to BPUI and the highest CD31 immunoexpression among examined constructs. Except Vwf, endothelial-related gene expression in BPEO had a later onset and was upregulated and well-balanced during in vivo incubation that induced late onset of Spp1 expression and pronounced osteocalcin immunoexpression at 2 and 8 wk. Tissue regression was noticed in BPEO constructs after 8 wk. CONCLUSION Ectopically implanted BPEO constructs had a favorable impact on vascularization and osteogenesis, but tissue regression imposed the need for discovering a more optimal EC/OB ratio prior to considerations for clinical applications.

Genetic Diversity [Working Title], 2020

The Mediterranean region encompasses countries that surround Mediterranean Sea. Due to its positi... more The Mediterranean region encompasses countries that surround Mediterranean Sea. Due to its position at the intersection of Eurasia and Africa it has often been a route of human migrations during history, which contributed to its high biodiversity. People living in this area had been exposed to the episodes of natural selection that led to the establishment of specific genetic variations, for which is thought to carry a certain adaptation. Some recent studies have shown that genetic adaptations are probably related to the immune defense against infectious pathogens. One of the most recognizable disease of the region is familial Mediterranean fever (FMF), a prototype of a monogenic autoinflammatory disease. FMF is predisposed by the mutations in the Mediterranean fever (MEFV) gene that encodes inflammasome regulatory protein - pyrin. Specific variations of several other genes have been proposed to confer a protection against Plasmodium malariae parasite. Some of these are hemoglobin S...

Clinical Implementation of Bone Regeneration and Maintenance [Working Title], 2020

Despite excellent self-regeneration capacity of bone tissue, there are some large bone defects th... more Despite excellent self-regeneration capacity of bone tissue, there are some large bone defects that cannot be healed spontaneously. Numerous literature data in the field of cell-based bone tissue engineering showed that adipose-derived stem cells (ADSCs) after isolation could be subsequently applied in a one-step approach for treatment of bone defect, without previous in vitro expansion and osteoinduction. However, standard approaches usually involve in vitro expansion and osteoinduction of ADSCs as an additional preparation step before its final application. Bioreactors are also used for the preparation of ADSC-based graft prior application. The commonly used approaches are reviewed, and their outcomes, advantages, disadvantages, as well as their potential for successful application in the treatment of bone defects are discussed. Difficulty in spontaneous healing of bone defects is very often due to poor vascularization. To overcome this problem, numerous methods in bone tissue engineering (BTE) were developed. We focused on freshly isolated stromal vascular fraction (SVF) cells and ADSCs in vitro induced into endothelial cells (ECs) as cells with vasculogenic capacity for the further application in bone defect treatment. We have reviewed orthotopic and ectopic models in BTE that include the application of SVFs or ADSCs in vitro induced into ECs, with special reference to co-cultivation.

International Orthopaedics, 2020

Purpose Given the great potential of macrophages in the processes of tissue repair and regenerati... more Purpose Given the great potential of macrophages in the processes of tissue repair and regeneration, the aim of our study was to examine the contribution that macrophages will have in osteogenic process when combined and implanted with blood clot (BC) and mineral bone substitute (MBS) in mice subcutaneous implantation model. Methods Three types of implants were constructed and implanted subcutaneously into BALB/c mice: (1) RMBM implants (made of resident tissue macrophages, BC and MBS), (2) BM implants (made of BC and MBS), and (3) M implants (made of MBS only) where the last two served as control implants. One, two, four and eight weeks after implantation implants were explanted, and histochemical, immunohistochemical, and histomorphometric analyses were performed. Results Increased vascularization, particularly pronounced two and four weeks after implantation and pronounced tissue infiltration in eight week term in RMBM implants compared with both other types, likewise the presence of osteoblast-like cells, osteoid-like structures, and more prominent osteopontin and osteocalcin immunoexpression in RMBM implants indicated more pronounced osteogenic process within them. Conclusion Our results suggest that macrophages deserve to be considered as a cell component when constructing implants in bone regenerative medicine strategies to improve bone fracture healing process.

Biomaterials in Clinical Practice, 2018

Acta Medica Medianae, 2017

Repair of bone defects can be supported by appropriate biomaterials, cells and regulatory signals... more Repair of bone defects can be supported by appropriate biomaterials, cells and regulatory signals, which is the basic principle of bone tissue engineering. The components of bone marrow and blood clot come in close contact with bone defects after injury. Since these structures represent the source of different cell types and regulatory signals, we wanted to examine their effect on osteoreparatory process in ectopic implants. Subcutaneous implantation was performed on male Balb/c mice. Bio-Oss ® biomaterial in the function of mineral matrix carrier was loaded with blood diluted with bone marrow cell suspension (MMB-type implants) or only with blood diluted with saline (MB-type implants, control). Implant extraction was performed 2, 8 and 12 weeks after implantation. MMBtype implants were characterized with more pronounced beginning of resorption in comparison with MB-type implants. High cell density of connective tissue was also preserved during the 12-weeks observation period in MMB-type implants, as well as good vascularity, which was most pronounced 8 weeks after implantation. Osteoblast-like cells and osteon-like structures could be observed. These results suggest that bone marrow in synergy with blood clot might have a stimulating effect on osteoreparation process.

Proceedings of the IV Advanced Ceramics and Applications Conference, 2017

Nanomaterials are nowadays widely used in various fields of biomedicine. Before the application o... more Nanomaterials are nowadays widely used in various fields of biomedicine. Before the application of biomaterials they have to be tested and fulfill some criteria. The first tests that should be performed after synthesis of some new nanomaterial with potential application in biomedical fields are biocompatibility tests. The aim of this study was to examine the influence of nanomaterial calcium phosphate/poly-(dl-lactide-co-glycolide) (CP/PLGA) on proliferation and adherence of HeLa cells in culture. For both proliferation and adherence examination, cells were treated with suspension of nanomaterial CP/PLGA at concentrations 5, 50 and 500 µg/mL, made in cell culture medium. There were four different types of treatment: (1) cells incubated with CP/PLGA for 3 days; (2) cells incubated with CP/PLGA for 6 days; (3) cells incubated first with CP/PLGA for 3 days and then for the next 3 days with medium and (4) cells incubated first with medium for 3 days and then for the next 3 days with CP/PLGA. Three days after incubation of HeLa cells with different concentrations of CP/PLGA nanoparticles’ suspension, the concentration of 5 µg/mL had mild inhibitory effect on proliferation. Increasing CP/PLGA concentration, there was stimulatory effect on cells’ proliferation. With prolonged incubation period, this dose dependence is lost. The highest adherence of HeLa cells was observed when cells were incubated with the highest examined concentration of CP/PLGA suspension, in both 3-day and 6-day incubation period. Based on the results obtained in our study, we can conclude that the effect of the suspension of nanomaterial CP/PLGA on proliferation and adherence of HeLa cells depends on the duration of incubation with the cells as well as the material concentration and type of the treatment.

$Research paper thumbnail of Ectopic osteogenic capacity of freshly isolated adipose-derived stromal vascular fraction cells supported with platelet-rich plasma: A simulation of intraoperative procedure$

Journal of Cranio-Maxillofacial Surgery, 2016

Bone defects represent a serious problem in cranio-maxillofacial surgery. Autologous adipose-deri... more Bone defects represent a serious problem in cranio-maxillofacial surgery. Autologous adipose-derived stromal vascular fraction (SVF) cells in combination with biological factors and bone substitutes were previously proposed as alternative to bone grafting. By simulating an intraoperative procedure we examined osteogenic capacity of the combination of two autologous components, freshly isolated adipose-derived SVF cells, and platelet-rich plasma (PRP), delivered on bone mineral matrix (BMM) carrier (SPB group) in mice ectopic bone forming model. Implantation of BMM only (B group) was a control. The presence of adipose-derived stem cells (ADSCs) in SVF was detected by immunocytochemical analysis. Expression of bone-and endothelial-related genes was compared between freshly isolated SVF and ADSCs obtained from SVF after in vitro cultivation. The implants were analyzed using expression analysis of bone-related genes at one, two, four and eight weeks and histochemical, immunohistochemical and histomorphometrical analyses at two and eight weeks after implantation. Freshly isolated adipose-derived SVF contained ADSCs and exhibited promising osteogenic and vasculogenic capacity. At two and four weeks, significantly higher expression of bonerelated genes was detected in SPB group compared to B group. The signs of osteogenic process were more pronounced in SPB than in B implants. By the end of experiment, percentage of infiltrated tissue and vascularization was significantly higher in SPB than in B implants. Adipose-derived SVF cells, PRP and BMM rapidly initiated osteogenesis what makes this combination promising candidate for treatment of bone defects.

Materials Research, 2016

In this study we prepared hydrogels based on 2-hydroxyethyl methacrylate (HEMA): PHEMA homopolyme... more In this study we prepared hydrogels based on 2-hydroxyethyl methacrylate (HEMA): PHEMA homopolymer and two terpolymers of HEMA, itaconic acid (IA) and two poly(alkylene glycol) (meth) acrylates (PAGM): poly(ethylene glycol) 6 acrylate (P(HEMA/IA/PAGM1)) and poly(propylene glycol) 5 methacrylate (P(HEMA/IA/PAGM2)). Hydrogels were synthesized by gamma-irradiated radical polymerization and subjected to swelling measurements and genotoxicity evaluation. Swelling studies confirmed that these hydrogels deserve consideration as biomaterials due to their ability to swell in phosphate buffer but maintaining physical integrity for a prolonged contact time after equilibrium state has been reached. Comet assay showed certain genotoxic effect following cell exposure to extracts of hydrogels, which was dependent on the concentration of extracts, chemical composition of hydrogels and the degree of crosslinking. The influence of concentration on genotoxicity was the most pronounced. The synthesis of these novel HEMA-based hydrogels should be optimized so as to reduce their toxicity and enable the use in clinical practice.