Sustained release of 17β-estradiol stimulates osteogenic differentiation of adipose tissue-derived mesenchymal stem cells on chitosan-hydroxyapatite scaffolds.

The aim of this study was to develop a 17β-estradiol (E2)-releasing scaffold-nanoparticle system in order to promote osteogenic differentiation of rat adipose tissue-derived mesenchymal stem cells (AdMSCs) for bone tissue regeneration. E2-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles with a diameter of ∼240 nm were produced via an emulsion-diffusion-evaporation method. Because of its higher encapsulation efficiency (54%), PLGA, which has a 65:35 composition, was chosen for the preparation of nanoparticles. Chitosan-hydroxyapatite (HA) scaffolds in macroporous structures with interconnected pores were prepared by combining microwave irradiation and gas-foaming techniques. PLGA nanoparticles were loaded onto scaffolds in 2 ways: via embedding after scaffold fabrication and during fabrication. While 100% of the loaded E2 was released during 55 days from scaffolds loaded by embedding, a controlled release behavior of E2 was observed over 135 days in scaffolds loaded during manufacture. The results of cell culture studies indicated that the controlled delivery of E2 from PLGA nanoparticles loaded on chitosan-HA scaffolds had a significant effect on the osteogenic differentiation of AdMSCs.