Short Segments of Electrospun Nanofibers Loaded with Curcumin Can Protect the Cells in Spheroids against Oxidative Stress

Oxidative stress in damaged or inflamed tissues presents a major barrier to the efficacy of cell-based therapies by impairing cell viability, function, and engraftment. Herein, we demonstrate a nanofiber-integrated three-dimensional spheroid platform that delivers Curcumin (Cur), a natural antioxidant, for cellular protection. Cur can be encapsulated in electrospun polycaprolactone (PCL) fibers, which are processed into short segments and coassembled with human mesenchymal stem cells to form spheroids. The integrated fibers enable a two-phase release profile of Cur while preserving spheroid morphology and maintaining cell organization. Under H₂O₂-induced oxidative stress, Cur-PCL-integrated spheroids showed improved cell viability and reduced mitochondrial reactive oxygen species compared with untreated controls. Unlike conventional nanoparticle-based systems that often rely on inefficient cellular uptake and can suffer from limited penetration in 3D aggregates, this fiber-segment approach provides a physically retained intraspheroidal depot that enables localized cytoprotection while preserving spheroid integrity, offering a scalable and injectable strategy for engineering resilient cell constructs. The system holds promise for improving the therapeutic performance of stem cell therapies in oxidative microenvironments associated with tissue injury and regeneration.