Long-term proliferation and delayed senescence of bone marrow-derived human mesenchymal stem cells on metformin co-embedded HA/Gel electrospun composite nanofibers

The current work was going to assess the efficacy of hyaluronic acid/Gelatin (HA/GEL) encapsulated with metformin-loaded mesoporous silica nanoparticles (MET@MSNs) on the prolonged in vitro proliferation of bone marrow-derived human mesenchymal stem cells (BM-hMSCs) without prompting aging. For this purpose, composite scaffolds consisting of MET and MET@MSNs in combination with HA were manufactured by convenient and green electrospinning technique. The surface morphology and biochemical characteristics of manufactured scaffolds were evaluated using FE-SEM, TGA, and FTIR. The enhanced proliferation rate and metabolic activity of the BM-hMSCs seeded on MET@MSNs incorporated into HA/Gel scaffolds (MET@MSNs HA/Gel NFs) were confirmed via PicoGreen and MTT test assay, respectively, over 21 days of culture. Moreover, the mRNA expression levels of senescence and stemness marker after a long-term in vitro culturing by qPCR. According to the high proliferation rate and proper metabolic activity of the BM-hMSCs after 21 days of culture on the MET@MSNs HA/Gel NFs, the prepared NFs represented great capacity for both initial and controlled release of MET. The obtained data from MTT and PicoGreen examination also revealed improved metabolic activity and expansion rate for BM-hMSCs grown on the MET@MSNs-NFs compared to the other treated groups after 1, 14 and 21 days of incubation. On the other hand, the hTERT and telomerase expression was significantly increased in BM-hMSCs cultured on MET@MSNs HA/Gel NFs compared to the control group. These results confirmed the capability of MET@MSNs HA/Gel NFs for persistent and controlled discharge of MET in the designing of a novel platform for neutralizing cellular aging and attaining adequate quantities of fresh BM-hMSCs for tissue engineering applications.