Topography and surface morphology of micrometer and nanometer scaled fibrous biomaterials are crucial for bioactive component encapsulation, release, promoting cell proliferation and interaction within biological environment. Specifically, for drug delivery and tissue repair applications, surface engineering provides control on both aspects in tandem. In this study, the bioactive component (ganoderma lucidum spore polysaccharide (GLSP)) was loaded into zein prolamine (ZP) fiber matrices via coaxial electrospinning (CES) technique. During the CES process, various outer layer enveloping fluids were used to modulate fiber topography in-situ (from 2D to 3D). SEM and water contact angle tests indicate enveloping media impact electrospun fiber diameter (ranging from 400 nm to 3.0 mu m) and morphologies (from flat ribbon-like to solid cylindrical structures), with the latter impacting GLSP release profile. Furthermore, CCK-8 assay assessment indicates fibroblast cell proliferation (L929 cell line), while cell extension was also observed for modified ZP fibers. The results demonstrate potential applications of modified fiber morphologies, which are tailored in-situ without impacting chemical stability and encapsulation.