Periferik sinir sistemi rejenerasyonu için iletken materyallerin geliştirilmesi ve etkinliğinin değerlendirilmesi

06.03.2018 tarihli ve 30352 sayılı Resmi Gazetede yayımlanan “Yükseköğretim Kanunu İle Bazı Kanun Ve Kanun Hükmünde Kararnamelerde Değişiklik Yapılması Hakkında Kanun” ile 18.06.2018 tarihli “Lisansüstü Tezlerin Elektronik Ortamda Toplanması, Düzenlenmesi ve Erişime Açılmasına İlişkin Yönerge” gereğince tam metin erişime açılmıştır.Sinir dokusu vücutta onarımı en zor olan dokuların başında gelir. Özellikle kaza sonucu meydana gelen sinir defektleri ve kayıplar başlıca sağlık sorunlarından biridir. Periferik sinir yaralanmaları bu tip yaralanmalarda başı çeker. Bu tür incinmeler travmatik hastaların %2,8'inde gerçekleşir ve çoğunlukla yaşam boyu süren fonksiyon kayıplarına veya bozukluklarına yol açar. Bunun yanında incinmelerin gerçekleşmesiyle beraber sinirsel ağrıların gözlenmesi de olasıdır. Bu sebeple, periferik sinir yaralanmaları bireylerin yaşam kalitesini olumsuz etkileyen sosyoekonomik etkilerinden dolayı önüne geçilmesi gereken sağlık sorunlarındandır. Aksonlar sinir hücreleri boyunca elektrik sinyallerinin iletimini sağlayan önemli sinirsel taşıyıcılardır. Periferik sistemde incinen aksonların yenilenmesi sinir fiberlerinin etrafını sararak myelin kılıfı oluşturan Schwann hücrelerinin çoğalmasıyla vuku bulur. 5 mm'den büyük defektlerde iki uç arasında bağlantıyı sağlayabilmek için sinir greftleri kullanılması gerekmektedir. Allogreftlerin ve otogreftlerin kullanımında doku uyumu gibi problemlerden dolayı sentetik greftler üzerinde yoğunlaşılmıştır. Bu sayede doku mühendisliğinin en önemli yaklaşımlarından biri alternatif sinir greftleri geliştirmek olmuştur. Bu greftler periferik sinir kanallarına kılavuz olacak şekilde kanal olarak tasarlanmıştır. Tamamen iyileşme sağlaması için biyobozunur olması gerekmektedir. Kılavuz kanallarını daha etkin hale getirmek amacıyla nanoteknolojinin gelişmelerinden faydalanılmıştır. Özellikle nanofiber ve nanotüplerin kanal yapılarının içine eklenmesi sinir aktivitelerini tetikleyen bir ortam oluşturmada önemli rol oynar. Bu çalışmada periferik sinir yaralanmalarıyla meydana gelen fonksiyon kayıplarında uygulanan cerrahi müdahalelerde kullanılabilecek yenilikçi ve etkin biyobozunur kompozit sistemler geliştirilmiştir. Geliştirilen sistemin biyobozunur sistem içerisinde akson yenilenmesini arttırıcı etkisi hücre çoğalmasını ve gelişimini destekleyen etken maddeler içermesiyle desteklenerek hastanın hızlı bir iyileşme süreci geçirerek yaşam kalitesinin korunması hedeflenmiştir. İletken ve toksik olmayan metalik nanoyapılarla desteklenerek sinirsel iletimin arttırılması ve bu sayede rejenerasyonun hızlandırılması ana hedefidir. Bu nanokompozit sistemden oluşan kılavuz kanalının vücuda yerleştirildikten sonra bozunmasıyla beraber sinir dokusu gelişerek kılavuz kanalının yerini alması amaçlanmıştır.Regeneration of nerve tissue is the slowest healing tissue in body. Especially the nerve defects and losts after accidents are ones of the main health problems. Peripheric nerve defects comes first in those injuries. These injuries are observed 2.8% of traumatic patients and it usually results function losts or disorders maintaining lifelong. Moreover, observation of nervous pain can be possible. Therefore, peripheric nerve degeneration is one of the health problems that should be prevented or treated due to socialeconomical effects that affecting human life quality of individuals. Axons are the essential nerve vehicles that carry electrical signals across the nerves. Regeneration of axon defects in peripheric systems occur with proliferation of Schwan cells which wraps the nerve fibers and generate myelin sheath. Nerve grafts must be used for the degeneration larger than 5 mm in order to obtain connection between two ends of the nerve defect. Due to tissue compatibility problem in use of allografts and autografts, synthetic grafts were focused. With this perspective, one of the important approach of tissue engineering became development of alternative nerve graft. These grafts are designed as conduit in order to guide peripheric nerve fibers. These grafts should also be biodegradable in order to provide complete regeneration. Nerve guide conduits containing variable pore structures indicate different production techniques. The inner part of these nerve conduits can be empty or fills with fibres and spongy structure. In order to make more effective nerve conduits, nanotechnological improvements were used. Especially addition of excellent conductive and biocompatible nanofibers and nanotubes into the nerve conduits have important roles in stimulation of nerve activates. In this study, novel and effective biodegradable nerve conduit systems will be developed to be use in surgical operations for fixing function losts arises from peripheric nerve defects. Nerve conduit made of this nanocomposite system is aimed to replace with nerve tissue. Therefore, structures belonging to nerve conduits in this project will be first in literature and patents

Sert doku destekleri olarak Biyobozunur kompozit sistemlerin hazırlanması ve karakterizasyonu :

In tissue engineering applications, use of biodegradable and biocompatible materials are essential. As the tissue regenerate itself on the material surface, the material degrades with enzymatic or hydrolytic reactions. After a certain time, natural tissue takes the place of the artificial support. Poly(ε-caprolactone) (PCL) is one of the preferable polymers used in the restoration of the bone defects due to its desirable mechanical properties and biocompatibility. Addition of inorganic calcium phosphate particles in PCL structures can improve the mechanical properties as well as osteoconductivity; and presence of an antibiotic can prevent infection that may occur at the defect site. In this study, three forms of biodegradable hard tissue supports which are bone fillers, bone regenerative membranes and 3D scaffolds were designed and prepared. As biodegradable bone fillers, composite microspheres containing gelatin and β-tricalcium phosphate (β-TCP) were prepared and characterized. Synthesized β-TCP particles were coated with gelatin at different weight ratios and the effects of β-TCP/Gelatin ratio on the morphology of the microspheres were evaluated. Also, a model antibiotic, gentamicin, was loaded to these microspheres and release behaviours of the drug and its antibacterial effect on E.Coli was determined. The selected composition of these microspherical bone fillers were used as additives in the preparation of bone regenerative membranes and scaffolds. For this purpose, microspheres were added into PCL solution and processed by either solvent casting or freeze-drying in order to prepare bone regenerative membranes or scaffolds, respectively. For every material, the ratio of constituents (microsphere and PCL) was altered in order to obtain optimum properties in the resulted hard tissue support structure. The effects of the ratio of the microspheres to PCL in terms of morphological, mechanical and degradation properties of composite films, as well as in vitro antibiotic release and antibacterial activities against E.Coli and S.Aureus were investigated. For scaffolds, the effects of the ratio of the microspheres to PCL on the morphological, mechanical, pore size distribution, degradation properties and in vitro antibiotic release were examined.M.S. - Master of Scienc

BİYOBOZUNUR POLİKAPROLAKTAN TEMELLİ KOPOLİMER SİSTEMLERİN DOKU MÜHENDİSLİĞİ İSKELE YAPILARI OLARAK SENTEZLENMESİ, KARAKTERİZASYON VE OPTİMİZE EDİLMESİ

BİYOBOZUNUR POLİKAPROLAKTAN TEMELLİ KOPOLİMER SİSTEMLERİN DOKU MÜHENDİSLİĞİ İSKELE YAPILARI OLARAK SENTEZLENMESİ, KARAKTERİZASYON VE OPTİMİZE EDİLMES

Zero-valent iron nanoparticles containing nanofiber scaffolds for nerve tissue engineering

Regeneration of nerve tissue is a challenging issue in regenerative medicine. Especially, the peripheral nerve defects related to the accidents are one of the leading health problems. For large degeneration of peripheral nerve, nerve grafts are used in order to obtain a connection. These grafts should be biodegradable to prevent second surgical intervention. In order to make more effective nerve tissue engineering materials, nanotechnological improvements were used. Especially, the addition of electrically conductive and biocompatible metallic particles and carbon structures has essential roles in the stimulation of nerves. However, the metabolizing of these structures remains to wonder because of their nondegradable nature. In this study, biodegradable and conductive nerve tissue engineering materials containing zero-valent iron (Fe) nanoparticles were developed and investigated under in vitro conditions. By using electrospinning technique, fibrous mats composed of electrospun poly(epsilon-caprolactone) (PCL) nanofibers and Fe nanoparticles were obtained. Both electrical conductivity and mechanical properties increased compared with control group that does not contain nanoparticles. Conductivity of PCL/Fe5 and PCL/Fe10 increased to 0.0041 and 0.0152 from 0.0013 Scm(-1), respectively. Cytotoxicity results indicated toxicity for composite mat containing 20% Fe nanoparticles (PCL/Fe20). SH-SY5Y cells were grown on PCL/Fe10 best, which contains 10% Fe nanoparticles. Beta III tubulin staining of dorsal root ganglion neurons seeded on mats revealed higher cell number on PCL/Fe10. This study demonstrated the impact of zero-valent Fe nanoparticles on nerve regeneration. The results showed the efficacy of the conductive nanoparticles, and the amount in the composition has essential roles in the promotion of the neurites