BiomaterialsJan 15, 2026

Iron oxide nanoparticles may help renew mitochondria and restore aging bone marrow environment

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 19, 2026

Abstract

KGM-PEG-SPIONs enhance donor mitochondrial quality and improve compatibility in senescent bone marrow cells.

Mitochondrial transfer from macrophages to bone marrow stem cells may improve treatment for age-related osteoporosis.
Chronic inflammation and metabolic dysfunction in aging bone marrow environments limit the efficacy of mitochondrial transfer.
KGM-PEG-SPIONs activate autophagy and promote the formation of essential mitochondrial components, improving donor mitochondria.
Functionalized mitochondria are transferred through gap junctions, leading to increased ATP production and enhanced cell function.
In aged osteoporotic models, these scaffolds may remodel immune environments and enhance bone formation.

Simplified

With the aging population, treating age-related osteoporosis remains challenging due to the dysfunctional bone marrow microenvironment characterized by chronic inflammation, metabolic dysregulation, and impaired mitochondrial function in senescent cells. While mitochondrial transfer from macrophages to bone marrow mesenchymal stem cells (BMSCs) offers a promising therapeutic avenue, its efficacy is limited in aged niches where donor mitochondria exhibit functional deficits and poor recipient compatibility. We engineered KGM-PEG-SPIONs, functionalized FeOnanoparticles that enhance donor mitochondrial quality via autophagy activation and Fe-S cluster biogenesis, promote M2 macrophage polarization, and improve compatibility with the oxidative and inflammatory environment of senescent BMSCs. These M2-like mitochondria are transferred through connexin 43 gap junctions, restoring membrane potential, ATP production, calcium homeostasis, and osteogenic differentiation in recipient cells. In aged osteoporotic models, KGM-PEG-SPION-functionalized scaffolds remodel immune niches and promote bone formation. By integrating organelle quality control with environment-adapted mitochondrial transfer, this strategy surpasses approaches focusing solely on transfer quantity or polarization, establishing a programmable nanoplatform for organelle-based regeneration. 3 4

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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

Iron oxide nanoparticles may help renew mitochondria and restore aging bone marrow environment

Abstract

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Funding

Competing interests

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