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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; Aydeger, 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 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 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 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 Neuroprotective Effects of Piceatannol on Olfactory Bulb Injury after Subarachnoid Hemorrhage (Mar, 10.1007/s12035-023-03306-x, 2023)(Springer, 2023) Akar, Ali; Oztopuz, Rahime Ozlem; Buyuk, Basak; Ovali, Mehmet Akif; Aykora, Damla; Malcok, Umit Ali[Anstract Not Available]
