Metformin-Loaded PCL/PVA Fibrous Scaffold Preseeded with Human Endometrial Stem Cells for Effective Guided Bone Regeneration Membranes.

Many studies have been devoted to investigating the potential of guided bone regeneration (GBR) membranes for bone defect reconstruction. Regardless of approaches for treating damaged bone tissues, a beneficial therapeutic strategy has remained a challenge. In this study, a novel GBR membrane with polycaprolactone (PCL) and poly(vinyl alcohol) (PVA) containing different concentrations of metformin (Met) for improving osteogenic properties was developed. The membranes were evaluated for their hydrophilicity, degradation rate, swelling ratio, drug release, mechanical properties, and biological responses. The results showed a significant increase in hydrophilicity, swelling ratio, and degradation rate and no significant changes in mechanical properties of PCL/PVA membranes with Met concentration enhancement. A decrease in cell viability cultured on the surface of the PCL/PVA membrane was seen when the amount of Met was changed from 10 to 15 wt %. The results of the in vitro quantitative real-time polymerase chain reaction (qRT-PCR) also confirmed the higher secretion of osteogenic-related genes in a PCL/PVA/Cell/10 wt % Met scaffold than in the PCL/PVA/Cell sample. Therefore, further in vivo studies were conducted using the electrospun PCL/PVA membrane containing human endometrial stem cells (hEnSCs) and 10% Met. Histopathological and histomorphometric results confirmed that PCL/PVA/hEnSCs/10 wt % Met has excellent potential to differentiate hEnSCs into osteogenic lineages and bone regeneration in calvarial defects of rats. The results of this study confirm the high potential of the PCL/PVA/10 wt % Met fibrous membrane preseeded with hEnSCs in GBR applications.