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Öğe Biomimetic 3D bioprinted bilayer GelMA scaffolds for the delivery of BMP-2 and VEGF exogenous growth factors to promote vascularized bone regeneration in a calvarial defect model in vivo(Elsevier, 2025) Alarcin, Emine; Akguner, Zeynep Puren; Ozturk, Ayca Bal; Yasayan, Gokcen; Ilhan-Ayisigi, Esra; Kazan, Aslihan; Guner, F. SenihaThe effective treatment of critical-sized bone defects requires a coordinated interaction between osteogenesis and angiogenesis. Inspired by natural bone tissue, we developed a bilayer vascularized bone construct using extrusion-based dual 3D bioprinting. The construct consists of two layers: a bone-mimetic layer, which includes highly methacrylated gelatin (GelMAHIGH), hyaluronic acid, alginate, osteoblast cells, and bone morphogenetic protein-2 (BMP-2) loaded polylactic-co-glycolic acid (PLGA) nanoparticles; and a vessel-mimetic layer, composed of low methacrylated gelatin (GelMALOW), alginate, endothelial cells, and vascular endothelial growth factor (VEGF)-loaded PLGA nanoparticles. These layers were designed to form hierarchical microstructures that enable sustained release of growth factor (GF) thereby stimulating both osteogenic and angiogenic processes. The nanoparticles were synthesized using a microfluidic platform, achieving a narrow size distribution. The hydrogel bioinks were systematically optimized for printability, and it was found that incorporation of nanoparticles improved their mechanical properties, surface roughness, degradability, and GF release profiles. Notably, GF release followed zero-order kinetics, ensuring consistent delivery over time. The bilayer scaffolds demonstrated superior cell proliferation and spreading compared to single-layer scaffolds, and in vivo experiments showed enhanced repair of calvarial bone defects. These findings highlight the significant clinical potential of bilayer scaffolds with sequential GF delivery for treating critical-sized bone defects.Öğe INNER EAR HISTOLOGICAL FINDINGS OF INTRATYMPANIC APPLICATION OF ENCAPSULATED GEL-BASED GENTAMICIN(2024) Aslan, Gulay Guclu; Arslan, Ilker Burak; Yesil-Celiktas, Ozlem; Vatansever, Seda; Çukurova, İbrahim; Aslan, Asım; Kazan, AslihanIntroduction: In this study, histopathological changes in inner ear after intratympanic application of gentamicin prepared in encapsulated gel formulation were investigated. Materials and Methods: 200 ?l Poloxamer 407 solution containing 10 mg gentamicin in encapsulated form was prepared. Fourteen adult guinea pigs were used for the study. In Group A gentamicin in encapsulated gel formulation, in group B 200 ?l Poloxamer 407 solution, in Group C gentamicin alone were applied intratympanically to the right ears by 0.3 cc (6 mg) 3 times in a week. One week later following intratympanic applications animals were sacrificed and inner ears were dissected for histologic evaluation. In 4 animals, left ears were used as negative control group (Group D). All specimens were dyed with TUNEL method. Apoptotic cells were counted in the cochlea and lateral semicircular canal ampulla. Results: The percent of TUNEL positive cells was higher in Groups B and C comparing to Group A in organ of Corti, and higher in Groups B and C comparing to Group A in spiral ganglion. In ampulla of the lateral semicircular canal, the percentage was higher in Group C comparing to Groups A and B. Conclusion: Histologic destruction caused by gentamicin on the ampulla of the lateral semicircular canal was observed less in application of encapsulated form of gentamicin than in application of gentamicin alone. Destruction of the cells in the organ of Corti and the spiral ganglion in encapsulated form application was also less than gentamicin alone application.Öğe Microencapsulation of Black Carrot Anthocyanins for Enhanced Thermal Stability(2024) Baysal, Elif; Kazan, AslihanPigments obtained from plants and algae are utilized as colour additives in food and pharmaceutical formulations due to the advantages of being non-toxic and possessing several biological activities. However, the low stability limits the utilization of natural pigments and therefore strategies such as chemical modification or encapsulation are required. This study aimed to improve the thermal stability of black carrot anthocyanins by microencapsulation. The effect of parameters such as concentration and flow rate of alginate solution, stirring rate and temperature of CaCl2 solution and needle diameter on the average size, polydispersity (PDI), and sphericity of alginate microparticles were examined. Optimum conditions were elicited as 2% concentration and 1 ml/min flow rate for alginate solution, 40 rpm stirring rate of CaCl2 solution at 4oC and 0.45 mm of needle size resulting in 462.4 ?m of particle size. Heat treatment was also applied and the retention efficiencies were determined as 96.92% and 75.82% for encapsulated and free anthocynanins, respectively. In addition, half-life of anthocyanin rich extract has been shown to increase from 7.5 h to 66.5 h by microencapsulation. These findings indicated the ability of alginate microparticles for the protection of black carrot anthocyanins from thermal degradation and improvement of storage stability.Öğe OLIVE LEAF EXTRACT INCORPORATED CHITOSAN FILMS FOR ACTIVE FOOD PACKAGING(2023) Kazan, Aslihan; Demirci, FatmaPackaging materials serve as a barrier to protect the food from the environment and new approaches with improved properties, such as active packaging, is gaining more attention nowadays. In this study, chitosan films containing olive leaf extract (OLE) as an additive were prepared and characterized in terms of mechanical, structural and biological properties. The addition of OLE improved not only the tensile strength (32 MPa) and elongation (9.3%) of chitosan films but also their barrier properties such as water vapor transmission rate of 657.52 g/m2day and moisture retention capability of 90.41%. Furthermore, chitosan films gained antibacterial properties with the addition of OLE and possessed a dose and time-dependent antioxidant activity compared to their extract-free equivalents. As a consequence, the present study suggests that chitosan films incorporated with OLE are a promising alternative as an active food packaging with enhanced mechanical, barrier, antioxidant and antibacterial properties.Öğe Valorization of Cydonia oblonga leaves as a source of bioactive compounds: process optimization and improvement of extract stability by encapsulation(Springer Heidelberg, 2025) Kazan, AslihanPlant-derived bioactive compounds are attracting more attention than ever which leads to search of new sources and optimization of extraction processes to achieve a sustainable system. The aim of this study was to investigate the utilization possibilities of Cydonia oblonga leaves which are released as a waste during quince production. In this study, microwave-assisted extraction (MAE) was applied and a statistical design was used to evaluate the effects of temperature, microwave power, and time on the extraction of phenolic compounds from waste quince leaves. Additionally, the leaf extract obtained at optimum extraction conditions was encapsulated by desolvation method, and empty and extract-loaded nanoparticles were characterized in terms of size, morphology, and thermal properties. For MAE, the optimum conditions were elicited as 39.52 degrees C of temperature, 300 W of microwave power, and 15 min of time with a total phenol content of 218.18 mg GAE/g, a total flavonoid content of 63.8 mg QE/g, and EC50 value of 9.45 mu g/mL. The obtained leaf extract was encapsulated in protein-based nanoparticles, and average particle size and encapsulation efficiency were calculated as 89.9 nm and 74.4%, respectively. Furthermore, the thermal stability of the leaf extract was enhanced by encapsulation compared to its free form. Consequently, Cydonia oblonga leaves were found to be a potential source for bioactive compounds and microwave-assisted extraction was suggested as a favorable approach to obtain higher extraction yields. Moreover, the improvement of the thermal stability of the leaf extract by encapsulation may contribute to successful valorization of this waste biomass in various applications.
