Cartilage tissue regeneration using kartogenin loaded hybrid scaffold for the chondrogenic of adipose mesenchymal stem cells

Abstract

In this paper, novel composite scaffold is developed based on the combination of a hydrogel and a controlled release drug delivery system for the regeneration of cartilage tissue. To fabricate the composite scaffold (PVA-PU-NP), polyvinyl alcohol was cross-linked by pre-polyurethane, which was used for the scaffold matrix. The PLGA nanoparticles (NPs) containing kartogenin was loaded inside the scaffold for chondrogenic induction. SEM and DLS results showed the particle size is about 250–300 nm with the zeta potential of −3.43 mV in a spherical morphology. The composite scaffold was characterized by several characterization techniques, including SEM, FT-IR, contact angle, degradation ratio and tensile strength evaluation. FT-IR spectroscopy validated the scaffold's effective synthesis and SEM data confirmed the porous structure of the scaffold with open pores of 120–160 μm. The release profile of kartogenin loaded onto the nanoparticles in PBS (pH = 7.4) was evaluated in 30 days and confirmed the controlled release of the drug. NPs and PVA-PU-NP scaffold are confirmed to be non-toxic, while increasing the concentration of kartogenin leads to an increase in the cytotoxicity of the studied NP-Scaffold. Chondrogenic differentiation of adipose-derived stem cells cultured on the scaffold were analyzed. RT-PCR studies showed that the expression of collagen type II and aggrecan were upregulated and the higher expression of collagen II, in comparison with collagen I and aggrecan was observed in the presence of scaffold/NP compared to the scaffold. Besides, H&E and immunostaining studies proved a homogeneous cartilage tissue formation with a normal histological structure was observed on the kartogenin loaded NP-Scaffold with the successful differentiation of mesenchymal stem cells to chondrocytes. In general, the results confirmed the successful and efficient differentiation of the mesenchymal stem cells to the chondrocytes on the PVA-PU-NP scaffold by the controlled release of kartogenin from hybrid scaffold.