Poly (l-lactic acid)-based modified nanofibrous membrane with dual drug release capability for GBR application

Electrospun multilayer nanofibers guided bone regeneration (GBR) with a new design were developed in this study. The synthesized multilayer GBR was composed of two distinct layers. Poly l-lactic acid (PLA) incorporated with simvastatin (SIM) was designed as PLA/SIM layer to contact with a bone defect. In addition, the hydrophilic gelatin (GT) containing thymol (THY) was fabricated as GT/THY layer to contact connective tissue, potentially for bacterial gathering. Due to the different chemical nature and weak cohesion of the hydrophilic and hydrophobic layers, hybrid fibers made of PLA/SIM and GT/THY were electrospun as cohesion promoters between these layers. The microstructure and characteristics of the synthesized multilayer substrate, named GT/PLA, were evaluated, and different fibrous monolayers were fabricated to determine the optimal concentrations of drugs. Scanning electron microscopy (SEM) images showed continuous, smooth, randomly aligned, and bead-free fibers. In addition, there were no drug particles on the fiber surfaces which displayed the good placement of those inside the fibers. The mats exhibited satisfactory tensile strength (4.60 ± 0.14 MPa) and favorable physicochemical properties, including proper porosity percentage (<50 %) and appropriate pore size. Suitable swelling behavior (293 ± 0.05 %) and adequate degradation rates were also approved by characterizing swelling and degradability in vitro. The GT/PLA membrane exhibited a prolonged and sustained SIM release and controlled THY release with high antibacterial efficiency. Cell viability, cell attachment assay, and nuclear staining using 4',6-diamidino-2-phenylindole (DAPI) showed that the designed GT/PLA substrate had good biocompatibility and cell attachment. Cell infiltration testing also showed that the cells were finely prevented by the outer layer (GT/THY). Overall, the obtained results in this study indicated the great potential of the prepared GT/PLA for use as a GBR which can develop osteogenic and antibacterial biomimetic periosteum optimizing the clinical application of GBR strategies.