Curcumin-loaded mesoporous silica nanoparticles/nanofiber composites for supporting long-term proliferation and stemness preservation of adipose-derived stem cells

The present research aims to design and develop a sustained drug release system to support the long-term proliferation of human adipose-derived stem cells (hADSCs) without losing their stemness and entering the cellular senescence through providing typical cell culture conditions. For this purpose, Curcumin-loaded mesoporous silica nanoparticles (CUR@MSNs) incorporated into Poly-epsilon-Caprolactone/Gelatin (PCL/GEL) hybrid were prepared via blend electrospinning and their impact was evaluated on cell adhesion, viability, proliferation and also the expression of senescence markers and stemness genes after a long-term in vitro culturing. The in vitro release findings proved that the MSNs incorporated into the electrospun nanofibers (NFs) allowed a sustained release of CUR. According to MTT and PicoGreen assays, the significant metabolic activity and proliferation of hADSCs were detected on CUR@MSNs-NFs after 14 and 28 days of incubation. Furthermore, CUR@MSNs-NFs showed better adhesion and spreading of hADSCs compared to other types of NFs. The sustained and prolonged delivery of CUR inhibited the stem cell senescence through the down-regulation of p16(INK4A) and up-regulation of hTERT. It also led to an increased stemness potency in growing hADSCs on the fibers. These results confirmed that the nanofiber-based sustained drug delivery system might provide a promising approach in designing highly programmable culture platforms to generate sufficient numbers of biologically functional hADSCs for clinical translation.