Publication: Kemik kanserine yönelik cisplatin ve kızılcık bitkisiyle güçlendirilmiş GelMA/ Hap içerikli doku iskelesi
Abstract
Bu tez çalışmasında, kemik kanseri tedavisinde biyomimetik doku iskelelerinin kullanımı üzerine bir araştırma gerçekleştirilmiştir. Çalışmanın temel amacı, kemik rejenerasyonunu destekleyen ve aynı zamanda kanser tedavisinde etkili olan bir hibrid doku iskelesi geliştirmektir. Bu bağlamda, metakrilatlanmış jelatin (GelMA) ve hidroksiapatit (Hap) temelli iskelelere, cisplatin ve kızılcık ekstraktı yüklenmiştir. İskelenin mekanik dayanımı, biyouyumluluğu, antikanser ve antioksidan özellikleri detaylı şekilde analiz edilmiştir. İlk olarak, GelMA/ Hap bazlı içeiğinde cisplatin ve kızılcık ekstraktı yüklü doku iskeleleri, Digital Light Processing (DLP) teknolojisi kullanılarak 3B baskı yöntemiyle üretilmiştir. İskelelerin kontrollü ilaç salım kapasitesi, ilaç salım kinetikleri ve biyobozunur yapıları in vitro deneylerle değerlendirilmiştir. Cisplatin ve kızılcık ekstraktının yarı maksimal inhibitör konsantrasyon (IC50) değerleri belirlenmiş ve bu ajanların hücre canlılığı üzerindeki etkileri hücre canlılık testi MethylthiazolyldiphenylTetrazolium (MTT) testi ile analiz edilmiştir. İskelenin karakterizasyonu; taramalı elektron mikroskobu (SEM), Fourier dönüşümlü kızılötesi spektroskopisi (FTIR) ve diferansiyel taramalı kalorimetri (DSC) yöntemleriyle gerçekleştirilmiştir. Ayrıca, mekanik testler ile iskelelerin kemik dokusuna uygun elastikiyet ve dayanım gösterdiği kanıtlanmıştır. Hücresel analizlerde insan fetal osteoblast (hFOB) hücreleri kullanılmış ve iskelenin osteoblast proliferasyonunu ve osteojenik farklılaşmayı teşvik ettiği gözlemlenmiştir. Sonuç olarak, geliştirilen GelMA/ Hap bazlı içeriğinde farklı miktarlarda cisplatin ilacı ve kızılcık ekstraktı bulunan doku iskelelerinin kemik kanseri tedavisinde umut vaat eden bir yöntem olduğu görülmüştür. Kontrollü ilaç salımı ve rejeneratif özellikler bir araya getirilerek hem kemoterapötik hem de osteojenik destek sağlayan bir sistem elde edilmiştir. Bu hibrid doku iskelesi hem kanser tedavisi hem de kemik dokusu yenilenmesi için klinik uygulamalar açısından önemli bir potansiyele sahiptir
In this thesis, a study was conducted on the use of biomimetic scaffolds in the treatment of bone cancer. The main purpose of the study was to develop a hybrid scaffold that supports bone regeneration and is also effective in cancer treatment. In this context, methacrylated gelatin (GelMA) and hydroxyapatite (Hap) based scaffolds were loaded with cisplatin and cranberry extract. The mechanical strength, biocompatibility, anticancer and antioxidant properties of the scaffold were analyzed in detail. First, GelMA/ Hap based scaffolds loaded with cisplatin and cranberry extract were produced by 3D printing using Digital Light Processing (DLP) technology. The controlled drug release capacity, drug release kinetics and biodegradable structures of the scaffolds were evaluated by in vitro experiments. The half-maximal inhibitory concentration (IC50) values of cisplatin and cranberry extract were determined and the effects of these agents on cell viability were analyzed by the cell viability test MethylthiazolyldiphenylTetrazolium (MTT) test. The characterization of the scaffold was carried out by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) methods. In addition, mechanical tests proved that the scaffolds showed elasticity and strength suitable for bone tissue. Human fetal osteoblast (hFOB) cells were used in cellular analyses and it was observed that the scaffold promoted osteoblast proliferation and osteogenic differentiation. As a result, it was seen that the developed GelMA/ Hap-based scaffolds containing different amounts of cisplatin drug and cranberry extract are a promising method in the treatment of bone cancer. By combining controlled drug release and regenerative properties, a system that provides both chemotherapeutic and osteogenic support was obtained. This hybrid scaffold has significant potential for clinical applications for both cancer treatment and bone tissue regeneration
In this thesis, a study was conducted on the use of biomimetic scaffolds in the treatment of bone cancer. The main purpose of the study was to develop a hybrid scaffold that supports bone regeneration and is also effective in cancer treatment. In this context, methacrylated gelatin (GelMA) and hydroxyapatite (Hap) based scaffolds were loaded with cisplatin and cranberry extract. The mechanical strength, biocompatibility, anticancer and antioxidant properties of the scaffold were analyzed in detail. First, GelMA/ Hap based scaffolds loaded with cisplatin and cranberry extract were produced by 3D printing using Digital Light Processing (DLP) technology. The controlled drug release capacity, drug release kinetics and biodegradable structures of the scaffolds were evaluated by in vitro experiments. The half-maximal inhibitory concentration (IC50) values of cisplatin and cranberry extract were determined and the effects of these agents on cell viability were analyzed by the cell viability test MethylthiazolyldiphenylTetrazolium (MTT) test. The characterization of the scaffold was carried out by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) methods. In addition, mechanical tests proved that the scaffolds showed elasticity and strength suitable for bone tissue. Human fetal osteoblast (hFOB) cells were used in cellular analyses and it was observed that the scaffold promoted osteoblast proliferation and osteogenic differentiation. As a result, it was seen that the developed GelMA/ Hap-based scaffolds containing different amounts of cisplatin drug and cranberry extract are a promising method in the treatment of bone cancer. By combining controlled drug release and regenerative properties, a system that provides both chemotherapeutic and osteogenic support was obtained. This hybrid scaffold has significant potential for clinical applications for both cancer treatment and bone tissue regeneration