Kontrollü ve Sıralı Büyüme Faktörü Salımı için Manyetik Silika/Aljinat Mikroküreler Kullanılarak Manyetik Duyarlı Kemik Doku İskelelerinin Geliştirilmesi

Abstract

This thesis aims to develop magnetically responsive composite tissue scaffolds that allow controlled and sequential release of growth factors in the field of bone tissue engineering. The developed system is composed of magnetic silica nanoparticles (MMSNs) and alginate (ALG) microspheres combined with a collagen/hydroxyapatite (COL/HA) matrix. Thus, synchronized release of osteogenic (BMP-2) and angiogenic (VEGF) growth factors with physiological timing was targeted. Firstly, silica nanoparticles were synthesized with an expanded pore structure, surface modified with amino groups and modified with citric acid coated Fe₃O₄ nanoparticles to obtain MMSN structures. Then, protein delivery and release profile of MMSNs loaded with bovine serum albumin as a model protein were investigated. In parallel, alginate microspheres synthesized by ionic cross-linking were designed for the prolonged release of growth factors. These carriers were combined with COL/HA matrix to form three dimensional porous tissue scaffolds. Characterization studies were performed by FT-IR, BET, DLS, VSM, XRD, TGA and SEM analysis. Release studies with magnetic field application revealed that MMSNs provide triggerable and controlled protein release, while ALG microspheres offer an early onset and sustained release profile. Biocompatibility analyses by MTT assay revealed that the scaffolds support cell viability. Furthermore, RT-qPCR analyses showed that the developed system promoted osteogenic differentiation by increasing the expression of RUNX2, COL1A1, ALP and OCN genes. The data revealed that magnetic field-triggered systems are effective in precisely controlling the timing of growth factor release and that a sequential release strategy can physiologically promote osteogenic differentiation. In this respect, the developed platform offers a promising strategy for the repair of critical bone defects. In conclusion, this thesis study has demonstrated the bone regeneration-promoting effects of magnetic field-sensitive composite systems based on controlled and sequential growth factor release and contributed to the development of new generation smart tissue scaffolds.