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Abstract
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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.
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