ArticleScience advances2026
A "Progenitor Cell Ark" hydrogel system for intervertebral disc regeneration via mitochondrial targeting and mitophagy enhancement.
Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
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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