Mastication-Induced Electrical Stimulation Activates Prg4+ Chondroprogenitors for Osteoarthritis Therapy

Shi-Yang Feng; Jing-Rong Cheng; Yu Qin; Jie Lei; Chen-Chen Gao; Hong-Ying Fu; Li-Ping Wu; Thanh D Nguyen; Xu-Liang Deng; Kai-Yuan Fu; Yang Liu

doi:10.1002/advs.75725

Mastication-Induced Electrical Stimulation Activates Prg4⁺ Chondroprogenitors for Osteoarthritis Therapy

Adv Sci (Weinh). 2026 May 19:e75725. doi: 10.1002/advs.75725. Online ahead of print.

Authors

Shi-Yang Feng^{1

2

3

4}, Jing-Rong Cheng^{2

3

4

5}, Yu Qin⁶, Jie Lei^{1

2

3

4}, Chen-Chen Gao^{1

2

3

4}, Hong-Ying Fu^{2

3

4

5}, Li-Ping Wu^{2

3

4

5}, Thanh D Nguyen^{7

8

9}, Xu-Liang Deng^{2

3

4

5}, Kai-Yuan Fu^{1

2

3

4}, Yang Liu^{2

3

4

5}

Affiliations

¹ Center For TMD and Orofacial Pain, Peking University School and Hospital of Stomatology, Beijing, China.
² NMPA Center for Innovation and Research in Regulatory Science and Beijing Key Laboratory of Digital Stomatology, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
³ National Center for Stomatology and National Clinical Research Center for Oral Diseases and NHC Research Center of Engineering and Technology for Computerized Dentistry, Beijing, China.
⁴ Beijing Key Laboratory of Biomaterials for Oral Disease, Peking University School and Hospital of Stomatology, Beijing, China.
⁵ Department of Dental Materials and Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, China.
⁶ Department of Orthopedics, Peking University Third Hospital, Beijing, China.
⁷ Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut, USA.
⁸ Institute of Materials Science, Polymer Program, University of Connecticut, Storrs, Connecticut, USA.
⁹ Department of Mechanical Engineering, University of Connecticut, Storrs, Connecticut, USA.

Abstract

Osteoarthritis (OA) is a whole-joint degenerative disease primarily driven by excessive mechanical overloading, yet current therapies fail to harness biomechanical cues to halt cartilage degeneration. Here, we developed mastication-driven magnesium-incorporated piezoelectric nanofibers (MagPie) that could convert joint loading into localized electrical stimulation while releasing Mg² ⁺ to neutralize the acidic microenvironment. Under mechanical stimulation, MagPie promoted chondrocyte anabolism and suppressed inflammation in vitro. In a rat temporomandibular joint OA model induced by overloading, MagPie, coupled with physiological mastication, restored the damaged osteochondral unit. Through single-cell transcriptomics, an electro-sensitive Prg4⁺ chondroprogenitor-like cell population was identified as a key mediator of cartilage regeneration. Mechanistically, MagPie-activated Prg4⁺ cells enhanced anabolic activity via the ECM-mediated FAK-PI3K-Akt axis and ameliorated the arthritic microenvironment by shifting macrophage polarization toward an anti-inflammatory phenotype. Genetic ablation of Prg4 attenuated the therapeutic efficacy of MagPie. Together, these findings uncover a mechanism of electrosensitive tissue repair and establish a 'trash-to-treasure' strategy that harnesses joint overloading to activate endogenous regenerative programs for OA therapy.

Keywords: cartilage regeneration; osteoarthritis; piezoelectrical stimulation; single‐cell RNA‐sequencing.

Abstract

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