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Öğe A 6-month in vivo study of polymer/mesenchymal stem cell constructs for cranial defects(Sage Publications Ltd, 2011) Aydın, Halil Murat; Korkusuz, Petek; Vargel, İbrahim; Kılıç, Emine; Güzel, Elif; Çavuşoğlu, Tarık; Pişkin, ErhanTwo biodegradable polymers, poly(L-lactide) and poly(epsilon-caprolactone) were blended (50/50) and used to produce polymeric scaffolds by the dual porogen approach using a salt leaching technique to create pores within the matrix, while supercritical-CO2 treatment was used to enhance the interconnectivity and to remove impurities from synthesis steps. The scaffolds were highly porous (porosity >90%) with interconnected pore morphologies. These biodegradable scaffolds were evaluated in Sprague Dawley rats for osteoconductive properties over a 6-month period. Bone specimens were analyzed after 1, 3, and 6 months, for bone healing and tissue response. The cortical bone remodeling by controlled osteoblastic and osteoclastic activities as well as the bone marrow elements recovery were semi-quantitatively examined for each group. Excellent integration and biocompatibility behavior was observed in all groups. No adverse tissue responses were observed.Öğe Cranial bone regeneration via BMP-2 encoding mesenchymal stem cells(Taylor & Francis Ltd, 2017) Vural, Altugan Cahit; Odabas, Sedat; Korkusuz, Petek; Saglam, Atiye Seda Yar; Bilgic, Elif; Cavusoglu, Tarik; Vargel, IbrahimCranial bone repair and regeneration via tissue engineering principles has attracted a great deal of interest from researchers during last decade. Here, within this study, 6mm critical-sized bone defect regeneration via genetically modified mesenchymal stem cells (MSC) were monitored up to 4 months. Cranial bone repair and new bone formations were evaluated by histological staining and real time PCR analysis in five different groups including autograft and bone morphogenetic protein-2 (BMP-2) transfected MSC groups. Results presented here indicate a proper cranial regeneration in autograft groups and a prospering regeneration for hBMP-2 encoding mesenchymal stem cells.Öğe Effect of Locally Administered Alendronate on Onlay Grafts(Amer Scientific Publishers, 2017) Tekin, Umut; Ozgul, Ozkan; Tuz, Hakan; Korkusuz, Petek; Kocyigit, Ismail Doruk; Atil, Fethi; Onder, M. ErcumentObjective: The present study compared the effects of local alendronate application on the osteogenesis of autogenous and xenogenous onlay grafts implanted in rabbit mandibles. Material and Methods: 28 New Zealand rabbits were used in this experimental animal study. The animals were randomly divided into 4 groups according to graft material as follows: D1: autogenous graft-saline; D2: 60% autogenous graft-40% alendronate D3: xenogenous bone graft-saline; D4: 60% xenogenous graft-40% alendronate. 3 histologic parameters were evaluated: the ratio of new bone formation to the total defect area, the active osteoblast-lined bone length, and the ratio of osteocyte-filled lacunae to total lacunae. At the same time, the grafted zones were evaluated using dual-energy X-ray absorptiometry (DEXA) and the Bone mineral density scores were measured. Results: The present study showed better results for the group receiving alendronate applied to autogenous graft when compared to other groups. Discussion: The administration of alendronate increases the resistance of autogenous graft; it may also enhance new bone formation and increase the viability of xenograft. Further animal studies supported with biomechanical tests are required prior to human studies.Öğe Effect of Use of Slow Release of Bone Morphogenetic Protein-2 and Transforming Growth Factor-Beta-2 in a Chitosan Gel Matrix on Cranial Bone Graft Survival in Experimental Cranial Critical Size Defect Model(Lippincott Williams & Wilkins, 2010) Canter, Halil Ibrahim; Vargel, Ibrahim; Korkusuz, Petek; Oner, Filiz; Gungorduk, Dilsad B.; Cil, Barbaros; Erk, YucelBone grafts, used for providing structural integrity of cranial vault remodeling, could not always integrate with the remaining bone structures. All efforts are focused on increasing incorporation of the applied bone grafts. Allografts were covered by chitosan so that slow release of bone morphogenetic protein-2 (BMP-2) and Transforming growth factor-beta-2 (TGF-beta-2) was achieved. Two hundred forty Wistar-Albino rats were distributed equally in 8 study groups. Study groups were designed as; defect group, autograft group, allograft group, chitosan group, allograft + chitosan, TGF-beta-2 group, BMP-2 group, and TGF-Beta-2 + BMP-2 group. Bone biopsies were obtained at second, eight, and 14th weeks. Bone regeneration was evaluated by morphologic studies detecting histologic bone healing and radiologic studies detecting bone density. Histologic findings were evaluated in 2 categories; tissue response to the implant and defect healing. Additionally, scanning electron microscopy for detailed morphologic evaluation was done. Bone density of the applied scaffold and the parietal bone at the same computed tomography section were measured in Hounsfield scale and this ratio was used for densitometry evaluations. Kruskal-Wallis test was used to analyze difference among groups according to the histologic and radiologic data. Pairwise comparisons were done using Mann-Whitney U test with Bonferroni correction. P < 0.05 was considered significant. In the morphologic studies, bone regeneration in BMP-2 group was found to be compatible with bone regeneration in gold standard autograft group and even better than it within 15 days. Chitosan is a biocompatible material. TGF-Beta-2 alone is not effective enough in bone regeneration; BMP-2 alone has a positive effect in every step of bone regeneration. Combining TGF-Beta-2 with BMP-2 does not lead to a better bone regeneration than using BMP-2 alone. A synergistic effect is not obtained by using these 2 factors together.Öğe Effects of alendronate on rate of distraction in rabbit mandibles(W B Saunders Co-Elsevier Inc, 2008) Tekin, Umut; Tuz, Hakan H.; Onder, Ercument; Ozkaynak, Ozkan; Korkusuz, PetekPurpose: Bisphosphonates are used for inhibiting bone resorption in several diseases. In this experimental study, the effects of alendronate on the mandibular distraction gap in rabbits at 2 different rates were evaluated. Materials and Methods: The study was performed using 15 New Zealand white rabbits. Group I consisted of animals with distraction at the rate of 1 mm/day. Group 2 consisted of animals with distraction at the rate of 2 mm/day. These experimental groups had a postoperative alendronate injection during the first 3 days of their distraction phase. Group 3 consisted of animals with distraction at the rate of 1 mm/day, without alendronate injections. Distraction was performed on only the left sides of all animals until a gap of 10 nun was achieved. On postoperative day 45, the animals were sacrificed, and the mandibles of all animals were evaluated radiographically and histologically, and with dual-energy x-rdy absorptiometry (DEXA). Radiographic images were also evaluated using transmission densitometry (TD). Results: Histologically, bone healing was found to be significantly accelerated in groups I and 2 compared with group 3 (P < .05). Bone healing was superior in group 2, but the difference was not statistically significant compared with group 1. The TD results revealed no statistical difference between experimental groups, whereas the results for group 2 showed significantly denser osteogenic formation in the distraction gap compared with group 3. There was a significant increase in mean bone mineral density in the experimental groups compared with the control group. Conclusion: Histologic, TD, and DEXA results showed that alendronate injections during the distraction phase may be effective in accelerating new bone formation in the distraction gap in rabbit mandibles. The TD results also support the concept that an administration of alendronate may allow a 2 mm/day elongation instead of I mm/day in the rabbit mandible. (C) 2008 American Association of Oral and Maxillofacial Surgeons.Öğe The Effects of Beta-blockers on Endothelial Nitric Oxide Synthase Immunoreactivity in the Rat Corpus Cavernosum(Elsevier Science Inc, 2010) Dogru, Mehmet Tolga; Aydos, Tolga Resat; Aktuna, Zuhal; Korkusuz, Petek; Zeybek, Dilara; Gorgu, Nart; Basar, Mehmet MuradOBJECTIVES To explain the mechanism of the effects of beta-blockers on endothelial dysfunction and release of nitric oxide from the endothelium. METHODS A total of 72 Sprague-Dawley rats were divided into 9 different groups as follows: group 1: control (n = 10), group 2: metoprolol (Beloc) 100 mg/kg/d (n = 7), group 3: carvedilol (Dilatrend) 50 mg/kg/d (n = 7), group 4: nebivolol (Vasoxen) 10 mg/kg/d (n = 6), group 5: estrogen receptor (ER) antagonist ICI 182.780 (Fluvestrant) 50 mu g/g (n = 10), group 6: nebivolol +ER antagonist (n = 8), group 7: androgen receptor (AR) antagonist (flutamide) 20 mg/kg (n = 7), group 8: nebivolol + AR antagonist (n = 7), and group 9: DMSO (solvent for ER antagonist) (n = 10). All beta-blockers were applied with gastric gavage after dilution with 5 mL of serum physiological; ER and AR were both applied intraperitoneally (i.p.) for 14 days. In the isolated rat cavernous tissues, endothelial nitric oxide synthase (eNOS) and ER and AR immunoreactivity were analyzed quantitatively. One-way analysis of variance and Tukey test were used for statistical analysis. RESULTS Although increased eNOS immunoreactivity was observed with nebivolol and nebivolol-flutamide in endothelial cells laying cavernous tissue, a lower score was observed after ICI-182.780 application, when compared with control cases. AR immunoreactivity in cavernosal endothelium was clearly higher with nebivolol. Higher H score and ER immunoreactivity were observed in the cavernous endothelium and smooth muscles in the nebivolol, carvedilol, and metoprolol groups when compared with control cases. CONCLUSIONS We showed that eNOS activity was increased in the nebivolol and nebivolol-flutamide groups, whereas it was decreased in the ICI 182.780 group. We believe that an ER-dependent mechanism triggered by nebivolol played a role in nitric oxide formation. UROLOGY 75: 589-597, 2010. (C) 2010 Elsevier Inc.Öğe Focused RF hyperthermia using magnetic fluids(Wiley, 2009) Tasci, T. Onur; Vargel, İbrahim; Arat, Anıl; Güzel, Elif; Korkusuz, Petek; Atalar, ErginHeat therapies such as hyperthermia and thermoablation are very promising approaches in the treatment of cancer. Compared with available hyperthermia modalities, magnetic fluid hyperthermia (MFH) yields better results in uniform heating of the deeply situated tumors. In this approach, fluid consisting of superparamagnetic particles (magnetic fluid) is delivered to the tumor. An alternating (ac) magnetic field is then used to heat the particles and the corresponding tumor, thereby ablating it. However, one of the most serious shortcomings of this technique is the unwanted heating of the healthy tissues. This results from the magnetic fluid diffusion from the tumor to the surrounding tissues or from incorrect localization of the fluids in the target tumor area. In this study, the authors demonstrated that by depositing appropriate static (dc) magnetic field gradients on the alternating (ac) magnetic fields, focused heating of the magnetic particles can be achieved. A focused hyperthermia system was implemented by using two types of coils: dc and ac coils. The ac coil generated the alternating magnetic field responsible for the heating of the magnetic particles; the dc coil was used to superimpose a static magnetic field gradient on the alternating magnetic field. In this way, focused heating of the particles was obtained in the regions where the static field was dominated by the alternating magnetic field. In vitro experiments showed that as the magnitude of the dc solenoid currents was increased from 0 to 1.8 A, the specific absorption rate (SAR) of the superparamagnetic particles 2 cm apart from the ac solenoid center decreased by a factor of 4.5, while the SAR of the particles at the center was unchanged. This demonstrates that the hyperthermia system is capable of precisely focusing the heat at the center. Additionally, with this approach, shifting of the heat focus can be achieved by applying different amounts of currents to individual dc solenoids. In vivo experiments were performed with adult rats, where magnetic fluids were injected percutaneously into the tails (with homogeneous fluid distribution inside the tails). Histological examination showed that, as we increased the dc solenoid current from 0.5 to 1.8 A, the total burned volume decreased from 1.6 to 0.2 cm(3) verifying the focusing capability of the system. The authors believe that the studies conducted in this work show that MFH can be a much more effective method with better heat localization and focusing abilities.Öğe Immunohistological Analysis of Normal and Osteoarthritic Human Synovial Tissue(J Michael Ryan Publishing Inc, 2005) Korkusuz, Petek; Dagdeviren, Attila; Eksioglu, Fatih; Ors, UlkenIntercellular communication mediated by cell surface antigens is important in the maintenance of synovial tissue (ST) integrity. Chronic inflammation is a common feature of osteoarthritis (OA). Cellular attachment to and migration into ST is one of the critical aspects of chronic inflammation. This study was undertaken to examine the tissue distribution of a broad spectrum of monoclonal antibodies (mAbs) containing tetraspan antigens (CD9, CD63, CD151), endothelial cell antigens (CD31, CD36, CD105, CD106, CD146), integrins (CD49a- f, CD29, CD41, CD51, CD61), CD39, CD98, CD99, CD143 and, CD147 supplied from fifth and sixth international workshops and conferences on human leukocyte differentiation antigens in a comparative manner in human OA and normal synovium. Ten primary OA patients and six normal individuals were included in this study. The average age of the patients was 65.0 +/- 8.3 years and the average age of the controls was 31.8 +/- 5.3 years. Sections were screened using an indirect immunoperoxidase method. Tetraspan antigens and CD98 presented rather unique staining pattern in OA synovium suggesting special roles for each antigen on the synovial lining layer (SLL). Endothelial cells and type A synoviocytes expressed CD31 and CD36 in OA, but only endothelium in normal subjects. Integrins presented a uniform staining pattern in both groups. There was a positive reaction in some of the ST stromal elements for CD143 in all specimens. In conclusion, human normal and OA synovium were comparatively reviewed by a broad spectrum of mAbs with special attention being given to their functional aspects. This data suggests a significant difference in antigenic phenotype of SLL cells in OA and ST not to be considered at a normal- like state in OA. The fact that their activation was independent of the degree of lymphocyte infiltration further emphasizes the possible central importance of SLL.Öğe Stem cell suspension injected HEMA-lactate-dextran cryogels for regeneration of critical sized bone defects(Taylor & Francis Ltd, 2014) Bolgen, Nimet; Korkusuz, Petek; Vargel, Ibrahim; Kilic, Emine; Guzel, Elif; Cavusoglu, Tarik; Piskin, ErhanHEMA-Lactate-Dextran cryogel scaffolds were produced by cryogelation. Mesencyhmal stem cells (MSC) were isolated from rat bone marrow. Critical sized cranial bone defects were created in rat cranium. Stem cells were injected inside the macropores of the cryogel scaffolds prepared from HEMA-Lactate-Dextran possessing the same dimensions with the defect and placed in the cranial bone. The cryogels placed in the defect without stem cells served as control. After selected time intervals the experimental sites were removed from the animals and new bone formation and tissue integration were investigated by histological analysis. The in vivo results exhibited osseous tissue integration within the implant and mineralized functionally stable bone restoration of the cranial defects. Tissue formation started in the macrospores of the scaffold starting from periphery to the center. A significant ingrowth of connective tissue cells and new blood vessels allowed new bone formation. Histological data demonstrated that new bone per total defect area ratio, were not significantly different in "scaffold-stem cells" group compared to that of "scaffold only" group on all time points. However, the blood vessel density was significantly higher in "scaffold-stem cells" group comparing to that of the "scaffold only" group on day 30. "Scaffold-stem cells" given group gave better tissue response score when compared to "scaffold only" group on day 180.Öğe Stem cells combined 3D electrospun nanofibrous and macrochannelled matrices: a preliminary approach in repair of rat cranial bones(Taylor & Francis Ltd, 2019) Isoglu, Ismail Alper; Bolgen, Nimet; Korkusuz, Petek; Vargel, Ibrahim; Celik, Hakan Hamdi; Kilic, Emine; Piskin, ErhanRepair of cranial bone defects is an important problem in the clinical area. The use of scaffolds combined with stem cells has become a focus in the reconstruction of critical-sized bone defects. Electrospinning became a very attracting method in the preparation of tissue engineering scaffolds in the last decade, due to the unique nanofibrous structure of the electrospun matrices. However, they have a limitation for three dimensional (3D) applications, due to their two-dimensional structure and pore size which is smaller than a cellular diameter which cannot allow cell migration within the structure. In this study, electrospun poly(epsilon-caprolactone) (PCL) membranes were spirally wounded to prepare 3D matrices composed of nanofibers and macrochannels. Mesenchymal stromal/stem cells were injected inside the scaffolds after the constructs were implanted in the cranial bone defects in rats. New bone formation, vascularisation and intramembranous ossification of the critical size calvarial defect were accelerated by using mesenchymal stem cells combined 3D spiral-wounded electrospun matrices.Öğe Tissue responses to novel tissue engineering biodegradable cryogel scaffolds: An animal model(Wiley, 2009) Bolgen, Nimet; Vargel, Ibrahim; Korkusuz, Petek; Guzel, Elif; Plieva, Fatima; Galaev, Igor; Piskin, ErhanBiodegradable macroporous cryogels with highly open and interconnected pore structures were produced from dextran modified with oligo L-lactide bearing hydroxyethylmethacrylate (HEMA) end groups in moderately frozen solutions. Tissue responses to these novel scaffolds were evaluated in rats after dorsal subcutaneous implantation, iliac submuscular implantation, auricular implantation, or in calvarial defect model. In no case, either necrosis or foreign body reaction was observed during histological studies. The cryogel scaffolds integrated with the surrounding tissue and the formation of a new tissue were accompanied with significant ingrowth of connective tissue cells and new blood vessels into the cryogel. The tissue responses were significantly lower in auricular and calvarial implantations when compared with the subcutanous and the submuscular implantations. The degradation of the scaffold was slower in bone comparing to soft tissues. The biodegradable cryogels are highly biocompatible and combine extraordinary properties including having soft and elastic nature, open porous structure, and very rapid and controllable swelling. Therefore, the cryogels could be promising candidates for further clinical applications in tissue regeneration. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 91 A: 60-68, 2009
