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Öğe 3D Bioprinting Strategies for Melatonin-Loaded Polymers in Bone Tissue Engineering(Wiley-V C H Verlag Gmbh, 2025) Aykora, Damla; Oral, Ayhan; Aydeğer, Cemre; Uzun, MetehanBone pathologies are still among the most challenging issues for orthopedics. Over the past decade, different methods are developed for bone repair. In addition to advanced surgical and graft techniques, polymer-based biomaterials, bioactive glass, chitosan, hydrogels, nanoparticles, and cell-derived exosomes are used for bone healing strategies. Owing to their variation and promising advantages, most of these methods are not translated into clinical practice. Three dimensonal (3D) bioprinting is an additive manufacturing technique that has become a next-generation biomaterial technique adapted for anatomic modeling, artificial tissue or organs, grafting, and bridging tissues. Polymer-based biomaterials are mostly used for the controlled release of various drugs, therapeutic agents, mesenchymal stem cells, ions, and growth factors. Polymers are now among the most preferable materials for 3D bioprinting. Melatonin is a well-known antioxidant with many osteoinductive properties and is one of the key hormones in the brain-bone axis. 3D bioprinted melatonin-loaded polymers with unique lipophilic, anti-inflammatory, antioxidant, and osteoinductive properties for filling large bone gaps following fractures or congenital bone deformities may be developed in the future. This study summarized the benefits of 3D bioprinted and polymeric materials integrated with melatonin for sustained release in bone regeneration approaches.Öğe A Novel Approach for Arteriovenous Fistula Maturation; Effects of Melatonin Loaded PLGA Nanofibers in Rats(Galenos Publ House, 2025) Aykora, Damla; Sahin, Serpil; Aydeger, Cemre; Yulek, Ozden; Alkan, Sevil; Oral, Ayhan; Jajere, Muhammad UmarAim: Arteriovenous fistula (AVF) is a cannulation method that is accessed by a peripheric vein and an artery. AVF provides vascular access for chronic kidney disease patients so they can receive hemodialysis. AVF could be created by surgical intervention and facilitates arterial to venous circulation for rapid recovery. However, AVF maturation depends on venous proliferation and luminal diameter which allows the optimum flow rate for continuing circiulation and hemodialysis. Due to multiple unexpected conditions, non-maturation of AVFs limits the efficacy of the hemodialysis so patients must receive another surgery for AVF cannulation. Materials and Methods: In this study, we aimed to utilize the effects of melatonin (MT), which is known to have antioxidant, anti-inflammatory, and antiapoptotic effects, to provide longer and more effective use of AVFs via a novel technique. For this purpose, firstly by electrospinning method, polylactic-co-glycolic acid (PLGA) nanofiber membranes were developed. After MT is loaded into the PLGA and characterized. Biodegradation and drug release profiles were analyzed. An in vivo study was performed in Wistar Albino male rats (n=18). Rats were randomly divided into three experimental groups; Sham, PLGA, and MT/PLGA respectively (n=6). AVF model was established in all groups between arteria carotica and vena jugularis under general anesthesia. The Sham group did not receive any treatment or biomaterial application. The developed membranes were placed onto the AVFs in PLGA and MT/PLGA groups. All rats were sacrificed on the 28th of the experiment. The anastomosis sites of all animals were harvested for histopathological analysis. Results: Our results showed MT/PLGA group indicated increased maturation levels conmpared to Sham group (p<0.05). Conclusion: The results showed that PLGA/MEL may be a promising material for early AVF maturation.Öğe Bone tissue engineering for osteointegration: Where are we now?(Springer, 2024) Aykora, Damla; Uzun, MetehanBone fracture healing is a challenging process, due to insufficient and slow tissue repair. Sufferers from bone fractures struggle with one-third of nonunion, display graft rejection, high-costed implantation, or chronic pain. Novel advances in tissue engineering presented promising options for this strain. Biomaterials for bone repair allow accelerated regeneration, osteoblastic cell activation, and enhanced bone remodeling. There is a wide range of biomaterials that are biocompatible, bioresorbable, and biodegradable and used for bone tissue regeneration, promoting osteoconductive and osteoinductive properties. The main aim of bone tissue engineering is to generate rapid and optimal functional bone regeneration through a combination of biomaterials, growth factors, cells, and various agents. Recently bone tissue engineering has been attracted to the use of bioactive glass scaffolds incorporated with polymers and patient-specific fabrication of the bone healing material by 3D bioprinting. There are promising future outcomes that were reported by several research. The present review provides an outlook for recent most common biomaterials in bone tissue engineering suggesting bone tissue engineering practices should have been proceeded to clinical application.Öğe Correction to: Neuroprotective Effects of Piceatannol on Olfactory Bulb Injury after Subarachnoid Hemorrhage (Mar, 10.1007/s12035-023-03306-x, 2023)(Springer, 2023) Akar, Ali; Öztopuz, Rahime Özlem; Büyük, Başak; Ovalı, Mehmet Akif; Aykora, Damla; Malçok, Ümit Ali[Anstract Not Available]Öğe Development of melatonin-embedded PLGA-PEG6000 nanofiber biomaterial, and investigation of the effects on abdominal adhesion formation(SAGE Publications Ltd, 2024) Gökçe, Oruç Numan; Aykora, Damla; Danışman, Merve; Demir, Ufuk; Aydeğer, Cemre; Süner, Salih Can; Oral, Ayhan; Karaboğa, İhsan; Uzun, MetehanAbdominal adhesions are still among the most common postsurgical peritoneal inflammation-related complications. Adhesion-related disorders are still highly costly and prevalent due to advances in surgical techniques, treatment methods, and various drugs. The present study aimed to investigate the effects of Poly (D,L-lactide-co-glycolide) (PLGA)- polyethylene glycol (PEG6000) Nanofiber + Melatonin on the abdominal adhesion model in rats. For this purpose, PLGA-PEG6000 Nanofiber + Melatonin matrix was fabricated and implanted in an experimental abdominal adhesion model in rats. Our study consisted of an in vitro and an in vivo part. The degradation and release profile of the matrix and Melatonin (Mel) embedded matrix was performed in vitro. In vivo, the procedure was carried out with 18 Wistar male rats. Rats were divided into three groups as follows: Sham, Matrix, and Mel + Matrix, respectively. Consequent to degradation and release profiling in vitro, an experimental adhesion model was created and fabricated pure matrix (2 × 2 cm2), and matrix (2 × 2 cm2, 0.25 mg melatonin/per matrix embedded) was applied to injury area in related groups. Intra-abdominal adhesion scores were determined on post-op 21st day, under general anesthesia. Following, cecum, peritoneal tissue, and adhesive bands were harvested. Macroscopic analysis (severity of adhesion formation), Hematoxlyn&Eosin and Masson’s Trichrome staining (for the examination of the levels of infiltration of inflammatory cells, fibrosis, and neovascularization) were performed for the evaluation of the effects of Mel embedded and pure matrix Our results indicated that PLGA-PEG6000 Nanofiber + Melatonin matrix was degraded completely in rats abdominal cavity and significantly reduced adhesion formation compared to other groups macroscopically (p < 0.05). On the other hand, the histopathological analysis indicated that the fabricated matrix reduced inflammatory cell infiltration, fibrosis, and neovascularization levels.Öğe Intranasal miRNAs-17/20 Administration Alleviates Early Brain Injury After Subarachnoid Hemorrhage in Rats(Springer, 2023) Malçok, Ümit Ali; Doğanlar, O.; Tüfekçioğlu, N. K.; Ovalı, Mehmet Akif; Aykora, Damla; Doğanlar, Z. B.; Büyük, B.; Uzun, MetehanEarly brain injury (EBI) in the first 24–72 h is the leading cause of mortality and disability related to subarachnoid hemorrhage (SAH). Both melatonin and microRNAs (miRs) are involved in the regulation of a number of neuronal molecular signaling procedures in the central nervous system, ranging from hypoxia, inflammation to neuronal apoptosis. The present study was performed to explore the effect of miRs-17/20 and combined treatment with melatonin on early brain injury after SAH and underlying molecular mechanisms in rats. In this study 54 Wistar albino rats were divided into six experimental groups: Sham, SAH, SAH + Melatonin, SAH+miRs-17/20 control, SAH+MEL+miRs-17/20, and SAH+MEL+miRs-17/20. The Garcia’s Neurological Scoring Scale and motor coordination tests were used for clinical observation. H&E staining was performed to evaluate pathological score. The gene expression levels were determined by qRT-PCR and key proteins were quantitated by Western blot assay. miRs-17/20 with or without melatonin treatment suppressed the expression and activity of both the HIF1/VEGF/MMPs and the IL6R/JAK2/STAT3 axis. miRs-17/20 with or without melatonin treatment also mitigated the clinical impairment, pyknosis, and edema in the hippocampus and cortex and neurodegeneration induced by SAH. Our results show that miRs-17/20 alleviated EBI by reducing hypoxic conditions, hypoxia-induced molecular signaling, and neuronal apoptosis.Öğe Kontrollü melatonin salımı yapan nanolif yapıda biyomateryal uygulamasının otogreft tamiri yapılan kritik kalvaryal kemik defektlerinin iyileşmesi üzerine etkilerinin araştırılması(Çanakkale Onsekiz Mart Üniversitesi, 2024) Aykora, Damla; Uzun, MetehanKemik kayıplarının hızlı onarımını ve hızlı kaynamasını sağlayacak osteoindüktif, osteokonduktif, biyouyumlu ve biyobozunur kompozit bir biyomateryal geliştirilmesi son yıllarda önemi artan bir konudur. Bu amaçla çalışmamızda biyouyumlu ve biyobozunur özellikleri bilinen PLGA yapısında in vivo ortamda yaklaşık olarak 28 günde biyobozunumunu tamamlayacak şekilde nanolifler üretilerek karakterizasyonu yapılmıştır. Nanolif yapısındaki bu biyomateryal içerisine osteoindüktif etkileri bilinen melatonin yerleştirilerek in vitro ortamda biyomateryalin 28 günlük ilaç salım profili ortaya konulmuştur. Üretilen, karakterizasyonu yapılan ve melatonin salım profili ortaya konulan bu biyomateryal daha sonra kritik kalvaryal kemik defekti oluşturularak otogreft ile tamir edilen sıçanlarda otogreftin ana kemik ile kaynaşması üzerine etkileri değerlendirilmiştir. Bu amaçla sıçanlardan 7, 14 ve 28. günlerde alınan kalvaryal kemik doku örneklerinde Hematoksilen-Eozin boyama ile yeni kemik oluşumu, Masson Trikrom boyama ile kolajen birikimi, Periyodik Asit Schiff boyama ile anjiyogenez ve Von Kossa boyama ile mineralizasyon düzeyleri belirlendi. İmmünohistokimyasal olarak Alkalen fosfataz, tartarat rezistans asit fosfataz, runt ilişkili transkripsiyon faktörü 2, kemik morfojenik protein 2 ve vasküler endotelyal büyüme faktörü immünoreaktiviteleri ölçüldü. Serum örneklerinden ise biyokimaysal analizler ile ALP düzeyleri belirlendi. Çalışmamız PLGA/MEL nanoliflerinin otogreft ile tamir edilen kritik boyutlu kalvaryal defektlerinin erken dönemde kaynaması üzerine etkilerini inceleyen ilk çalışmadır. Çalışmamızdan elde ettiğimiz sonuçlar ürettiğimiz PLGA/MEL nanoliflerinin otogreft uygulanan kemik kırıklarıda, otogreftin ana kemik ile erken kaynamasını sağlamak üzere umut vadedici olduğunu göstermektedir.Öğe Neuroprotective Effects of Piceatannol on Olfactory Bulb Injury after Subarachnoid Hemorrhage(Springer, 2023) Akar, Ali; Öztopuz, Rahime Özlem; Büyük, Başak; Ovalı, Mehmet Akif; Aykora, Damla; Malçok, Ümit AliSubarachnoid hemorrhage (SAH) accounts for 5% of all stroke cases and is responsible for significant permanent brain and neurological damage within the first few days. Loss of smell is one of those neurological disorders following olfactory bulb injury after SAH. Olfaction plays a critical role in several aspects of life. The primary underlying mechanism of olfactory bulb (OB) injury and loss of smell after SAH remains unknown. Piceatannol (PIC), a natural stilbene, possesses anti-inflammatory and anti-apoptotic effects against various diseases. In this study, we aimed to investigate the potential therapeutic effects of PIC on OB injury following SAH at molecular mechanism based on SIRT1, inflammatory (TNF-α, IL1-β, NF-κB, IL–6, TLR4), and apoptosis (p53, Bax, Bcl-2, caspase-3)-related gene expression markers and histopathology level; 27 male Wistar Albino rats were used in a pre-chiasmatic subarachnoid hemorrhage model. Animals were divided into groups (n = 9): SHAM, SAH, and PIC. Garcia’s neurological examination, brain water content, RT-PCR, histopathology, and TUNEL analyses were performed in all experimental groups with OB samples. Our results indicated that PIC administration significantly suppressed inflammatory molecules (TNF-α, IL–6, IL1-β, TLR4, NF-κB, SIRT1) and apoptotic molecules (caspase-3, p53, Bax). We also evaluated edema levels and cell damage in OB injury after SAH. Ameliorative effects of PIC are also observed at the histopathology level. Garcia’s neurological score test performed a neurological assessment. This study is the first to demonstrate the neuroprotective effects of PIC on OB injury after SAH. It suggests that PIC would be a potential therapeutic agent for alleviating OB injury after SAH.Öğe The Role of miR-330-3p in UV-induced Photokeratitis: A Pilot Experimental Study(Galenos Publ House, 2025) Eroglu, Huseyin Avni; Yavuz, Basak; Aydeger, Cemre; Erdogan, Hakika; Aykora, DamlaAim: Ultraviolet (UV) radiation-induced ocular diseases pose a growing challenge to public health. In recent years, miRNA-based therapeutics have gained attention in the treatment of ocular diseases. miR-330-3p has anticarcinogenic, anti-inflammatory, and anti-apoptotic effects. This study aimed to investigate the effects of miR-330-3p against photokeratitis following UV radiation. Materials and Methods: Eighteen Wistar albino male rats were randomly divided into three groups (n = 6) : control, UV, and UV+eye drop. Chronic exposure to UV radiation was conducted for 30 days, 2 hours a day. One mu l of miR-330-3p-based eye drops was applied to the UV+eye drop group once daily for 7 days. Following the treatments, eye tissues were harvested and evaluated microscopically. Results: There was no statistically significant difference between groups in inflammation, neovascularization, epithelial proliferation, and collagen density parameters. However, the edema levels in the UV group increased compared to the control and UV+eye drop groups (all p < 0.001 ) The collagen density, however, increased in the UV group and decreased in the UV+eye drop group, but the results did not indicate a significant difference (p > 0.05) Conclusion: miR-330-3p presents a promising treatment option for corneal damage arising from photokeratitis. Our study is the first to explore the alleviating effects of miR-330-3p in photokeratitis, yielding encouraging results.Öğe UV ile Indüklenen Fotokeratitis Üzerine miR-330-3p Uygulamasının Rolü: Pilot Çalışma(2025) Eroğlu, Huseyin Avni; Yavuz, Başak; Aydeğer, Cemre; Erdogan, Hakıka; Aykora, DamlaAmaç: Ultraviyole (UV) radyasyon ile indüklenen oküler hastalıklar büyüyen bir halk sağlığı sorunudur. Son yıllarda yapılan çalışmalar miRNA-tabanlı tedavilerin önemini artırmaktadır. miRNA’lardan biri olan miR-330-3p anti-karsinojenik, anti-enflamatuvar ve anti-apoptotik etkileri mevcuttur. Bu bilgiler ışığında çalışmamızın amacı UV radyasyonu sonucundaki fotokeratitise karşı miR-330-3p’nin etkilerini incelemektir. Gereç ve Yöntem: Çalışmada 18 adet erkek Wistar Albino rat kontrol, UV ve UV+göz damlası olmak üzere üç farklı gruba ayrılmıştır. Otuz gün süresince günde 2 saat kronik UV radyasyonuna maruz bırakılmıştır. Bunu takiben 7 gün süresince UV+göz damlası grubuna 1 µL miR-330-3p içeren göz damlası uygulaması yapılmıştır. Son uygulamadan 24 saat sonra hayvanlar sakrifiye edilerek histopatolojik incelemeler için uygun koşullarda saklanmıştır. Bulgular: Yapılan mikroskobik incelemeler sonucunda enflamasyon, neovaskülarizasyon, epitel proliferasyonu ve kolajen densitesi parametrelerinde gruplar arasında istatistiksel olarak bir farklılık belirlenmedi. Bununla birlikte istatistiksel olarak farklılık olmamasında rağmen kolajen densitesinin UV grubunda Kontrol grubuna göre yükseldiği ve göz damlası uygulamasının bunu düzenlediği görüldü. Ödem parametresi UV grubunda hem kontrol hem de UV+göz damlası grubuna göre istatistiksel olarak anlamlı şekilde yüksek olduğu ortaya koyuldu (her iki p-değeri p<0,001). Sonuç: Çalışmamızda miR-330-3p’nin fotokeratit üzerine etkileri ortaya koyulmuştur. miR-330-3p, fotokeratitten kaynaklanan umut verici bir tedavi seçeneği olarak görülmektedir.
