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

TL;DR

A nanofiber-based platform delivers curcumin to protect cells in 3D spheroids from oxidative stress, improving cell survival and function.

Contribution

A novel fiber-segment approach provides localized cytoprotection in 3D cell spheroids without relying on nanoparticle uptake.

Findings

Curcumin-loaded electrospun fibers improve cell viability under oxidative stress.

The fiber segments maintain spheroid structure and enable two-phase curcumin release.

The system offers a scalable strategy for resilient cell therapies in oxidative environments.

Abstract

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.

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