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Ultrasound-Responsive Piezo-Fenton-Like Microspheres for Modulating Mitochondrial Membrane Potential to Alleviate
Xiaohu Li1,2, Fan Wang2, Qianyi Li3
1Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China.
Advanced Materials (Deerfield Beach, Fla.)
|July 31, 2026
Summary
This study introduces an ultrasound-activated microsphere system to repair degenerated intervertebral discs by restoring mitochondrial membrane potential. The novel approach effectively modulated mitochondrial function and preserved disc height in vivo.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Mitochondrial Biology
Background:
- Degenerated intervertebral disc repair is hindered by the inability of current treatments to precisely control mitochondrial membrane potential (MMP).
- Aberrant MMP is a key factor in the pathophysiology of degenerative disc disease.
Purpose of the Study:
- To develop an ultrasound-activated system for precise recalibration of MMP in degenerated intervertebral disc tissue.
- To investigate a novel piezo-driven Fenton-like system for targeted mitochondrial modulation.
Main Methods:
- Development of ultrasound-activated piezo-driven Fenton-like microspheres (PF@MS) using Fe-BTO.
- Utilizing ultrasound to trigger piezopotential for iron valence modulation and proton consumption.
- Employing a boronate ester-based delivery strategy for cellular association via clathrin-mediated endocytosis.
Main Results:
- The PF@MS system successfully upregulated MMP from pathological to physiological levels.
- The system demonstrated self-limiting reactivity, preventing hyperpolarization through pH feedback.
- In vivo studies showed rescued autophagic flux (8% to 35%) and preserved 89% of intervertebral disc height.
Conclusions:
- Mechanically modulated metabolic reprogramming via ultrasound-responsive biomaterials offers a promising therapeutic strategy for degenerative diseases.
- The developed piezo-Fenton-like system effectively targets mitochondrial dysfunction in intervertebral disc degeneration.
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