Dextran/PLGA Core/shell Structured Ultrafine Fibers And Their Applications In Controlled Release Of VEGF

With high specific surface area, high porosity and a physical structure similarity to the natural extracellular matrix, ultrafine fibrous membranes prepared via electrospinning has been considered as an ideal method to product tissue engineering scaffolds recently. Coaxial electrospinning is a new electrospun technique to fabricate continuous composite ultrafine fibers with a unique core/shell structure. By using the core/shell fibers, in which the core polymer encapsulates growth factors and the shell one controls their diffusion rate out of the fibers, steady controlled release behaviors could be obtained.In this paper, fibrous membranes of poly(lactic-co-ε-glycolic acid) (PLGA) and core/shell Dextran(DEX)/PLGA were produced by electrospinning and coaxial electrospinning, respectively. The morphology of ultrafine fibers was observed under scanning electron microscope and transmission electron microscope. The water uptake measurements showed that the DEX/PLGA membrane held the highest value up to 1073±93%, much higher than the value of the electrospun PLGA membrane, 88.7±22.0%, due to introduction of DEX component and the core/shell structure. The mechanical properties of electrospun membranes were evaluated by tensile tests, and the results indicated that the tensile strength and the elongation of DEX/PLGA membranes reduced to a certain extent, attributing to the core of DEX.Fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) were encapsulated in the DEX/PLGA membrane and observed by a laser confocal scanning microscope. It was found that the protein inside the core/shell fibers distributed continuously and uniformly. Three kinds of fibrous membranes containing BSA were produced by coaxial electrospinning at different inner/outer solution flow rates of 0.1/0.6 mL/h, 0.2/0.6 mL/h and 0.3/0.6 mL/h, respectively. The results showed that the release rate of BSA became faster with increasing the core flow rate, which was up to 73.8±1.0%, 77.0±0.44% and 81.5±0.73% after 28 d, respectively. Vascular endothelial growth factor (VEGF) was loaded in the DEX/PLGA fibrous membrane and its release could sustain for more than 28 days.In order to evaluate the bioactivity of released VEGF in vivo, the electrospun DEX/PLGA membranes with or without loading VEGF were subcutaneously implanted in C57Bl/6J mices, and retrieved from subcutaneous pockets after 2 weeks and 4 weeks, respectively. The resulting neovascularization response was monitored and compared with respect to each other. Results exhibited that the electrospun DEX/PLGA membrane with a combination of VEGF displayed the highest density of blood vessels.