Tenogenic differentiation of human adipose derived mscs on a novel tendon scaffold by GDF-5 supplementation


Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Mühendislik Fakültesi, Mühendislik Bilimleri Bölümü, Türkiye

Tezin Onay Tarihi: 2018

Öğrenci: MUSTAFA BAHADIR GÜNER

Danışman: DİLEK KESKİN

Özet:

Tendon injuries are a significant part of musculoskeletal wounds. Even though tendon wound healing mechanisms provide regeneration after injuries, reduced function of the tendon usually occurs due to limitations of the native healing mechanism. Tendon tissue engineering (TTE) is proposed to repair the injured tendon by a scaffold integrated with biological factors. Therefore, aim of this thesis was to design 3D scaffold, by combining healthy and wounded extracellular matrix (ECM) structure of the tendon, together with stem cells and growth factor. 3D scaffolds were produced by Wet electrospun unaligned poly-ε-caprolactone (ESPCL) or PCL-Gelatin (ESPCL-Gel) fibers to mimic wounded ECM structure of tendon wrapped by aligned poly-ε-caprolactone fibers (FSPCL) produced by Rotary jet spinning to mimic healthy ECM structure of tendon. ESPCL or ESPCL-GeL fibers within FSPCL fibers not only improved the mechanical properties of 3D scaffolds but also provided better attachment and viability of fibroblasts. Furthermore, cell alignment was observed for all groups. Moreover, ESPCL-GeL in FSPCL scaffold showed higher fibroblast attachment and viability. Consequently, FSPCL/ESPCL-Gel scaffold was considered as the most suitable scaffold for TTE. Then, human adipose derived mesenchymal stem cells (HADMSCs) on FSPCL/ESPCL-Gel scaffold were induced with different concentration of growth differentiation factor 5 (GDF-5). The results revealed that HADMSCs with 100 ng/ mL of GDF-5 showed better proliferation, tenogenic differentiation, hydroxyproline production. As a conclusion, FSPCL/ESPCL-Gel 3D scaffold integrated with ADMSCs and GDF-5 showed promising results for TTE applications.