Unconventional Core–Shell Architecture of <scp>PCL</scp> –Soy Protein Nanofibers for Tunable Bioactive Scaffolds

ABSTRACT Electrospun polymeric scaffolds with core–shell architectures enable precise control over component distribution, release kinetics, and mechanical reinforcement, making them attractive for biomedical applications. However, plant‐protein based systems remain limited by poor aqueous stability and the need for toxic crosslinkers. This work introduces an inverted coaxial electrospun scaffold composed of a soy protein isolate (SPI)/poly(ethylene oxide) (PEO) shell and a poly(ε‐caprolactone) (PCL) core—an architecture not previously reported. The design exposes bioactive SPI at the fiber surface while maintaining integrity through the PCL core, achieving the rarely realized combination of surface bioactivity and structural stability. Oxidized sucrose, a natural and non‐toxic crosslinker, combined with thermal treatment, provides a green route to water‐stable, protein‐rich fibers without compromising morphology or biocompatibility. Scanning and transmission electron microscopy revealed uniform fiber diameters (~570 to 670 nm) and preserved interfaces after crosslinking. Surface analysis confirmed SPI/PEO predominance, while swelling and degradation in PBS showed intermediate behavior between PCL and SPI‐only meshes. Human dermal fibroblasts exhibited high viability, absence of cytotoxicity, and alignment‐dependent morphology. Overall, these SPI/PEO‐PCL scaffolds combine bioactivity, tunable fiber orientation and sustainable fabrication, highlighting their potential as temporary extracellular matrices for tissue engineering and regenerative medicine.