Kıkırdak Doku Mühendisliği için Nanopartikül / Hidrojel Bazlı Kompozit Yapıların Geliştirilmesi
| dc.contributor.advisor | Duman, Memed | |
| dc.contributor.author | Aksoy Körpe, Didem | |
| dc.date.accessioned | 2021-10-13T06:49:42Z | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2020-12-24 | |
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| dc.identifier.uri | http://hdl.handle.net/11655/25450 | |
| dc.description.abstract | Bioactive structures with unique biophysical and chemical properties of nanoparticles give great hope for the future development of tissue engineering applications. The purpose of this study to develop gelatin methacrylate (GelMA) hydrogel scaffold, functionalized with alginate-chitosan core-shell nanoparticles to enhance chondrogenic differentiation. Firstly, core-shell nanoparticles were synthesized with chitosan and alginate biopolymers. Different preparation conditions were applied to achieve monodisperse alginate- chitosan core-shell nanoparticles at nanoscale. Monodisperse alginate-chitosan core-shell nanoparticles which were prepared by modified protocol were measured to be 60 ± 3 nm. Different preparation conditions were applied to obtain optimum loading efficiencies and release profiles of growth factors (transforming growth factor beta-1 (TGF β-1) and insulin like growth factor-1 (IGF-1)) in the formation of the dual nanoparticular release system. According to the chosen preparation condition, the loading efficiency of TGF -1 and IGF-1 was 93.34 ± 0.51 and 91.92 ± 0.22%, respectively. When the 21 days release profile results were evaluated, the amounts of TGF β-1 and IGF-1 were measured as 15.86 ± 0.30 and 28.71 ± 2.27 ng/mL, respectively. Then, GelMA hydrogels were synthesized by photopolymerization method. The prepared nanoparticles and adipose tissue derived mesenchymal stem cells were encapsulated into GelMA hydrogels and incubated in vitro for 3 weeks. The effects of hydrogel, loaded and unloaded core-shell nanoparticles encapsulated hydrogels were evaluated by biochemical and histological analysis on chondrogenesis of adipose tissue derived mesenchymal stem cells. In the presence of chemical cues (chondrogenic medium), the content of DNA in the group containing TGF -1 and IGF-1loaded nanoparticles in hydrogel increased by 1.71 and 5.98 times, respectively, compared to the groups with and without nanoparticles on day 21. On the other hand, it was determined that glycosaminoglycan (GAG) production (573.60 ± 1.60 µg/sample) was significantly induced in the group containing both chemical cues and nanoparticles. In addition to biochemical assays, histological analyzes such as GAG and Type-II collagen staining also showed that the application of chemical and biophysical cues were increased GAG and Type-II collagen depositions. In summary, hydrogel scaffold functionalized with nanoparticles successfully occurred suitable environment for cartilage formation and thus it is a promising construct for cartilage tissue engineering applications. | tr_TR |
| dc.language.iso | tur | tr_TR |
| dc.publisher | Fen Bilimleri Enstitüsü | tr_TR |
| dc.rights | info:eu-repo/semantics/openAccess | tr_TR |
| dc.rights | Attribution-NonCommercial-NoDerivs 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/us/ | * |
| dc.subject | Çekirdek-kabuk nanopartikül | tr_TR |
| dc.subject | Aljinat | tr_TR |
| dc.subject | Kitosan | tr_TR |
| dc.subject | Jelatin metakrilat hidrojel | tr_TR |
| dc.subject | Doku mühendisliği | tr_TR |
| dc.subject | Kondrogenezis | tr_TR |
| dc.subject.lcsh | Sağlık mühendisliği | tr_TR |
| dc.title | Kıkırdak Doku Mühendisliği için Nanopartikül / Hidrojel Bazlı Kompozit Yapıların Geliştirilmesi | tr_TR |
| dc.title.alternative | Development of Nanoparticle / Hydrogel Based Composite Structures for Cartilage Tissue Engineering | |
| dc.type | info:eu-repo/semantics/doctoralThesis | tr_TR |
| dc.description.ozet | Nanopartiküller benzersiz biyofiziksel ve kimyasal özelliklere sahip biyoaktif yapılardır ve doku mühendisliği uygulamalarının gelecekteki gelişimi için büyük umut vaad etmektedirler. Bu çalışmanın amacı, kondrojenik farklılaşmayı arttırmak için aljinat-kitosan çekirdek-kabuk nanopartikülleri ile fonksiyonlaştırılmış jelatin metakrilat (GelMA) hidrojel iskelesini geliştirmektir. İlk olarak, kitosan ve aljinat biyopolimerleriyle çekirdek-kabuk nanopartiküler sentezlenmiştir. Nano ölçekte monodispers aljinat-kitosan çekirdek-kabuk nanopartiküllerini elde etmek için farklı hazırlama koşulları uygulanmıştır. Modifiye edilmiş protokol ile hazırlanan monodispers aljinat-kitosan çekirdek-kabuk nanoparçacıklarının boyutları 60 ± 3 nm olarak ölçülmüştür. İkili nanopartiküler salım sisteminin oluşturulmasında büyüme faktörlerinin (transforme edici büyüme faktörü beta-1 (TGF β-1) ve insülin benzeri büyüme faktörü-1 (IGF-1)) optimum yükleme verimliliklerini ve salım profillerini elde etmek için farklı hazırlama koşulları uygulanmıştır. Seçilen hazırlama koşullarına göre, TGF β-1 ve IGF-1'in yükleme verimlilikleri sırasıyla % 93.34 ± 0.51 ve 91.92 ± 0.22'dir. 21 günlük salım profilleri sonuçları değerlendirildiğinde, TGF β-1 ve IGF-1 miktarları sırasıyla 15.86 ± 0.30 ve 28.71 ± 2.27 ng/mL ölçülmüştür. Daha sonra fotopolimerizasyon yöntemi ile GelMA hidrojelleri sentezlenmiştir. Hazırlanan nanopartiküller ve yağ dokusu kökenli mezenkimal kök hücreler GelMA hidrojellerine kapsüllenmiştir ve in vitro olarak 3 hafta inkübe edilmiştir. Hidrojelin ve yüklü ve yüksüz çekirdek-kabuk nanopartiküller enkapsüle edilmiş hidrojellerin yağ dokusu kökenli mezenkimal kök hücrelerin kondrogenezi üzerindeki etkileri biyokimyasal ve histolojik analizler ile değerlendirilmiştir. Kimyasal etmenler (kondrojenik ortam) varlığında, hidrojel içindeki TGF β-1 ve IGF-1 yüklü nanopartiküller içeren gruptaki DNA içeriği, 21. günde nanopartikül olan gruplarda olmayan gruplara kıyasla sırasıyla 1.71 ve 5.98 kat artmıştır. Öte yandan, kimyasal etmenler ve nanopartiküller içeren grupta glikozaminoglikan (GAG) üretiminin (573.60 ± 1.60 µg/numune) önemli ölçüde indüklendiği belirlenmiştir. Biyokimyasal analizlere ek olarak, GAG ve Tip-II kolajen boyama gibi histolojik analizler de kimyasal ve biyofiziksel etmenlerin uygulanmasının GAG ve Tip-II kolajen birikimlerini artırmış olduğunu göstermiştir. Özetle, nanopartiküllerle işlevselleştirilmiş hidrojel iskelesi, kıkırdak oluşumu için uygun bir ortam sağlamıştır ve böylece kıkırdak doku mühendisliği uygulamaları için umut verici bir yapı olmaktadır. | tr_TR |
| dc.contributor.department | Nanoteknoloji ve Nanotıp | tr_TR |
| dc.embargo.terms | Acik erisim | tr_TR |
| dc.embargo.lift | 2021-10-13T06:49:42Z | |
| dc.funding | Bilimsel Araştırma Projeleri KB | tr_TR |
| dc.subtype | project | tr_TR |
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