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In this study, based on the collection process, three-dimensional aligned fiber scaffolds from gelatin and zein protein were manufactured using Forcespinning®. The homogeneous blending of gelatin:zein (1:4) showed improved tensile and good hydrophobic properties (water contact angle of 115 °C). Cell viability, adhesion, proliferation, and drug release were measured. The cell viability was studied with human fibroblasts and a low cytotoxic effect was observed. Berberine drug release was measured and sustained release rate was observed over 15 days. The morphologic features, prolonged drug release, and cytotoxicity results suggest that these fibers could be appropriate for drug delivery and tissue engineering applications.