Science advancesOct 14, 2026

A Hydrogel System for Spinal Disc Repair by Targeting Cell Energy Centers and Boosting Cell Cleanup

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 15, 2026

Abstract

The Progenitor Cell Ark significantly improved intervertebral disc structure and function in severe IVDD rat models.

A triple-layered hydrogel microsphere system was developed for targeted cell delivery and environmental support.
The outer layer contains nucleus pulposus progenitor cells to replenish lost cells in degenerated discs.
The inner layer features a nanozyme that targets mitochondria to reduce oxidative stress and enhance cellular health.
In vitro tests showed that the nanozyme protected progenitor cells from damage and improved mitochondrial function.
The treatment promoted neo-tissue formation and restored biomechanical function better than traditional therapies.

Simplified

Intervertebral disc degeneration (IVDD), driven by progenitor cell loss and oxidative stress, remains a major clinical challenge with limited effective regenerative therapies. Here, we present a "Progenitor Cell Ark," a triple-layered hydrogel microsphere system designed for synergistic cell delivery and microenvironment remediation. The Ark comprises an outer nucleus pulposus progenitor cell (NPPC) layer for cell replenishment, a middle GelMA/HAMA scaffold for support, and an inner SS31-modified ultrasmall Prussian blue nanozyme (SS31-UPN) layer that specifically targets mitochondria to scavenge ROS and promote mitophagy. In vitro, SS31-UPN effectively protected NPPCs from oxidative damage, restored mitochondrial function, and enhanced mitophagy. Critically, in severe IVDD rat models, the Progenitor Cell Ark significantly improved intervertebral disc structure, promoted neo-tissue formation, and restored biomechanical function, outperforming cell or bioscaffold therapy alone. Mechanistically, we demonstrate that SS31-UPN's mitochondrial targeting enhances mitophagy, drives ECM and energy metabolic remodeling, and preserves NPPC stemness, thereby creating a proregenerative milieu. This integrated "cell-in-a-box" strategy offers a robust platform for reversing IVDD and holds notable translational potential for regenerative medicine.

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A Hydrogel System for Spinal Disc Repair by Targeting Cell Energy Centers and Boosting Cell Cleanup

Abstract

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