Fabrication and characterization of a multi-functional GBR membrane of gelatin-chitosan for osteogenesis and angiogenesis.

Guided bone regeneration (GBR) membranes are widely used to treat bone defects. In this study, sequential electrospinning and electrospraying techniques were used to prepare a dual-layer GBR membrane composed of gelatin (Gel) and chitosan (CS) containing simvastatin (Sim)-loaded poly(lactic- co -glycolic acid) (PLGA) microspheres (Sim@PLGA/Gel-CS). As a GBR membrane, Sim@PLGA/Gel-CS could act as a barrier to prevent soft tissue from occupying regions of bone tissue. Furthermore, compared with traditional GBR membranes, Sim@PLGA/Gel-CS played an active role on stimulating osteogenesis and angiogenesis. Determination of the physical, chemical, and biological properties of Sim@PLGA/Gel-CS membranes revealed uniform sizes of the nanofibers and microspheres and appropriate morphologies. Fourier-transform infrared spectroscopy was used to characterize the interactions between Sim@PLGA/Gel-CS molecules and the increase in the number of amide groups in crosslinked membranes. The thermal stability and tensile strength of the membranes increased after N-(3-dimethylaminopropyl)-N9- ethylcarbodiimide/N-hydroxysuccinimide crosslinking. The increased fiber density of the barrier layer decreased fibroblast migration compared with that in the osteogenic layer. Osteogenic function was indicated by the increased alkaline phosphatase activity, calcium deposition, and neovascularization. In conclusion, the multifunctional effects of Sim@PLGA/Gel-CS on the barrier and bone microenvironment were achieved via its dual-layer structure and simvastatin coating. Sim@PLGA/Gel-CS has potential applications in bone tissue regeneration. Typical membranes were divided into osteogenic and barrier layers. The osteoblast layer promoted the adhesion and proliferation of MC3T3-E1 cells and HUVECs, whereas the barrier layer effectively inhibited the aggressive growth of L929 cells. [Display omitted] • Compared with traditional guided bone regeneration (GBR) membranes, the simvastatin in poly(lactic- co -glycolic acid) microspheres with gelatin and chitosan (Sim@PLGA/Gel-CS) proven with multiple functions in preventing occupy growth, and stimulating osteogenesis and angiogenesis that was hoped to obtain multi-functional GBR membranes. • PLGA microspheres among Gel-CS fibers used as a drug-release system enabled prolonged release of simvastatin, which maintained the local dose and avoided the side effects of systemic administration. • In addition to the Sim coating, Sim@PLGA/Gel-CS was prepared as two layers with different structures: an osteogenic layer with loose fibers containing Sim@PLGA microspheres and a barrier layer with compact fibers. This design is beneficial for preventing soft tissue damage and promoting bone tissue repair. [ABSTRACT FROM AUTHOR]