Gradient scaffolds are needed for interface tissue regeneration. In this study, a technique combining electrospinning and electrospraying was developed for preparing poly(L-lactide-co-glycolide) (PLGA) fiber-microsphere scaffolds for loading bioactive substances in gradient amounts. The gradient fiber-microsphere scaffolds contain two sheets of electrospun membranes and a sheet of microspheres loaded with bioactive substances in gradient amounts between the electrospun membranes. The morphologies of the gradient scaffolds were characterized and bovine serum albumin (BSA) was loaded as a model bioactive substance. The amount of BSA-loaded microspheres decreased gradually along the length of the gradient scaffold. The addition of poly (ethylene glycol) significantly improved the hydrophilicity of the gradient scaffold and the release behavior of BSA with respect to the gradient became apparent, with differences in the release amounts along the length of the gradient scaffold being observed. The biocompatibility of the gradient scaffold was verified using MC3T3-E1 pre-osteoblastic cells. The study demonstrated that the combination of electrospinning and electrospraying was a feasible method for the preparation of gradient scaffolds for potential applications in interface tissue engineering.
