Doku mühendisliği yaklaşımını kullanarak yapay retina yapımı.

Millions of people are affected by retinal diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP, night blindness). Retinal tissue engineering has potential to become a valid therapeutic approach to regenerate retina. The aim of this study was to construct a biomimetic retinal tissue substitute by using biocompatible and natural polymers and in vitro techniques. For this purpose, a retinal pigment epithelial (RPE) cell monolayer was formed on an electrospun silk fibroin mesh to mimic Bruch’s membrane. Results showed that RPE could proliferate and form a cell layer on the fibroin mesh. A HUVEC layer was constructed separately by microfabrication of a fractal tree design using photocrosslinkable methacrylated hyaluronic acid (HAMA) hydrogel to mimic the vasculature of choroid. To improve HUVEC adhesion in the design methacrylated collagen and methacrylated gelatin were immobilized in them using photolithography. It was seen that HUVEC could adhere only on the microchannels of the pattern and, form tubular structures at late culture periods. The co-culture studies in non-contact mode due to separation of the two cell types by the fibrous mat demonstrated that RPE cells on Bruch’s membrane could change the cell morphology, proliferation and thickness of vascular pattern that was formed by HUVECs in microchannels.M.S. - Master of Scienc

In vitro koşullarda kemik tümör modeli geliştirilmesi.

Osteosarcoma is one of the most common types of primary bone cancerous tumor. The structure of this tumor is solid, hard and irregular. Three dimensional (3D) models mimicking tumor tissue are needed for screening efficacy of the anticancer drugs for an effective personalized therapy. This study describes the design and production of a 3D bone tumor model (BTM) by using tissue engineering approach, and shows its capability to assess the efficacy of an anticancer drug. The model consists of two parts: (1) poly(lactic acid-co-glycolic acid) (PLGA)/beta-tricalcium phosphate (β-TCP) scaffold seeded with human fetal osteoblastic cells (hFOB) and human umbilical vein endothelial cells (HUVECs) (serve as the healthy microenvironment around the bone tumor tissue), and (2) collagen sponge seeded with human osteosarcoma cells (Saos-2) (mimic the tumor tissue). The second part is inserted in the central cavity of PLGA/β-TCP scaffold to form 3D BTM. Responsiveness of the developed model to anticancer drug, doxorubicin, was studied as an indicator of mimicking of bone tumor. Confocal micrographs on day 21 of incubation present migration of HUVEC cells to the tumor region. Increase in expression of angiogenic factors (VEGF, bFGF, and IL-8) in the tumor component also confirms cell migration. Doxorubicin demonstrated high efficacy when applied to the BTM model, and resulted in a 7-fold decrease in viability and apoptosis of Saos-2 cells (measured by caspase-3 enzyme activity). These show the suitability of the model in screening drug efficacies for personalized treatments.Ph.D. - Doctoral Progra

FEN BİLİMLERİ ENSTİTÜSÜ/LİSANSÜSTÜ TEZ PROJESİ

DOKU MÜHENDİSLİĞİ YAKLAŞIMINI KULLANARAK YAPAY RETİNA YAPIM

DOKU MÜHENDİSLİĞİ YAKLAŞIMINI KULLANARAK YAPAY RETİNA YAPIMI

DOKU MÜHENDİSLİĞİ YAKLAŞIMINI KULLANARAK YAPAY RETİNA YAPIM

Construction of a Retina Substitute by Using Tissue Engineering Approach

Construction of a Retina Substitute by Using Tissue Engineering Approac

RETİNA HASARLARININ TEDAVİSİNDE KULLANILMAK ÜZERE DOKU MÜHENDİSLİĞİ YÖNTEMİYLE YAPAY BRUK MEMBRANI KONSTRÜKSİYONU

Bu çalışmanın amacı, retina rejenerasyonunda önemli bir yere sahip olan ve retinal pigment endotellerinin fonksiyonlarını düzenleyen Bruk membranını aslına uygun biçimde doğal biyopolimerler ve in vitro teknikleri kullanarak oluşturmaktır. İpek fibroini matrisi içine Bruk membranının biyokimyasal kompozisyonuna benzetmek için karıştırılan kollajen, kondroitin sülfat ve laminin gibi hücre dışı matriks biyomolekülleri konulacaktır. Elektroeğirme tekniği ile nanofiber katman oluşturulucak, bunun üzerine retina pigment epitel hücreleri (RPE), retinanın görevi için çok önemli olan fotoreseptör hücrelerinin işlevini ve yaşamasını desteklemek için ekilecektir. RPE hücrelerine besin ve oksijen sağlamanın yanında biyokimyasal destek ve hücreler arası iletişim sağlanması için karyokapiler damar ağı yapısını taklit eden ve mikrofabrikasyonla oluşturulmuş hidrojel mikrokanalları içine kapiler endotelleri ekilecektir. Böylelikle altta hidrojel yapı içinde endotel hücreler ve bundan lifsi bir yapay Bruk membranıyla ayrılmış RPE hücreleri olacaktır. Endotel ve retina pigment epitel hücrelerinin birlikte yaşamasının sağlanması için ko-kültür yöntemi kullanılması planlanmaktadır. Yapay Bruk membranı, RPE ve karyokapiler katmanlar bir arada in vivo ortamda denenerek bu yapının retina bozukluğunun tedavisine uygunluğu incelenecektir

Hydrogels in Regenerative Medicine

Hydrogels are soft, jelly-like, polymeric networks with very high water retention capacity. They are made from natural materials or synthetic polymers. They are very important for the biomedical field because of the similarity between their mechanical and chemical properties and that of the extracellular medium, the microenvironment of a cell. They can be used in cell loaded form. High water content of the hydrogels is very suitable even without the cells in mimicking the hydrated tissues or viscous bodily fluids where they serve as a lubricant or a shape forming material. Actually cells do not like to adhere to very highly hydrophilic structures so they are very useful in applications where non-adherence is sought, like prevention of adhesion of tissues after a surgery. On the other hand, when we need the cells to attach to the hydrogels we make some chemical modifications on the material such as attaching cell adhesive arginine–glycine–aspartic acid (RGD) amino acid sequences. In this chapter the types, the sources of their starting materials, the methods of insolubilization, the network formation, the methods to use to control their properties, and their biomedical applications have been presented. Among the applications discussed are drug delivery systems, tissue engineering scaffolds, wound dressings, anti-adhesive membranes, and meshes