Engineered M2 macrophage-derived extracellular vesicles reprogram mitochondrial metabolism to alleviate temporomandibular joint cartilage degeneration

Sep 30, 2026

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Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disorder marked by progressive cartilage matrix degradation, and current clinical treatments provide mainly symptomatic relief. Disease progression is linked to mitochondrial dysfunction that triggers chondrocyte inflammation and extracellular matrix breakdown. Curcumin-loaded M2 macrophage-derived extracellular vesicles (Cur@M2-EVs) were engineered by ultrasonic encapsulation to scavenge ROS, restore mitochondrial membrane potential, and shift metabolism toward oxidative phosphorylation. Transcriptomics indicated that Cur@M2-EVs primarily reduce inflammation by suppressing Thbs1 expression, and Cur@M2-EVs were further embedded in PEGDA hydrogel microspheres to enable sustained release and improved lubrication. In an MIA-induced rat model, intra-articular Cur@M2-EVs@PEGDA significantly alleviated cartilage destruction and improved joint lubrication.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

TMJ anatomy and TMJOA pathology

Current clinical interventions and limitations

Macrophage polarization and M2-derived extracellular vesicles

Rationale for mitochondrial regulation and sustained delivery

Materials Today Bio 36 (2026) 102674 Contents lists available at ScienceDirect Materials Today Bio journal [homepage:](homepage: www.journals.elsevier.com/materials-today-bio)[ www.journals.elsevier.com/materials-today-bio](homepage: www.journals.elsevier.com/materials-today-bio) | Engineered M2 macrophage-derived extracellular vesicles reprogram mitochondrial metabolism to alleviate temporomandibular joint cartilage degeneration
Weiwen Gea,* , Lei Qib,*, Yun Wang c,*, Jing Wang b, Xin Fangb, Shixue Leid, Dan Lind,*, Lei Zhang b,**, Shanyong Zhang a,***
a Department of Oral Surgery, Shanghai Ninth People’s Hospital, College ofStomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory ofStomatology & Shanghai Research Institute ofStomatology, Shanghai, 200011, PR China
b Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute ofStomatology, Shanghai, 200011, PR China
c Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China d Intelligent Inspection and Diagnostics Health Service Platform, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, PR China | | | | --- | --- | --- | | A R T I C L E I N F O | | A B S T R A C T | | Keywords:
Engineered extracellular vesicles Mitochondria metabolism
ECM degradation
TMJOA
Temporomandibular joint osteoarthritis Hydrogel microspheres | | Temporomandibular joint osteoarthritis (TMJOA) is a degenerative joint disease characterized by progressive degradation of the cartilage matrix. Current clinical interventions mainly offer symptomatic relief but fail to halt disease progression. The pathogenesis of TMJOA is driven by mitochondrial dysfunction, which promotes both chondrocyte inflammation and extracellular matrix breakdown. To address these issues, an integrated therapeutic system was developed by encapsulating curcumin into M2 macrophage-derived extracellular vesicles (Cur@M2-EVs) through ultrasonic processing. In vitro studies demonstrated that Cur@M2-EVs effectively attenuated inflammatory responses and cartilage matrix degradation by scavenging reactive oxygen species (ROS), restoring mitochondrial membrane potential, and shifting cellular metabolism from glycolysis back to oxidative phosphorylation. Furthermore, transcriptomic analysis and experimental validation revealed that Cur@M2-EVs alleviate chondrocyte inflammation primarily by suppressing Thbs1 expression. To enable sustained drug release and enhance joint lubrication, Cur@M2-EVs were further encapsulated within poly (ethylene glycol) diacrylate (PEGDA) hydrogel microspheres, forming the Cur@M2-EVs@PEGDA system. In a monosodium iodoacetate (MIA)-induced rat model ofTMJOA, intra-articular injection of Cur@M2-EVs@PEGDA microspheres significantly alleviated cartilage destruction and improved joint lubrication. This study proposes a novel diseasemodifying strategy for TMJOA treatment by integrating mitochondrial regulation, immunomodulation, and sustained lubricating release within a single platform, offering a promising therapeutic approach for this challenging condition. | 1. Introduction The temporomandibular joint (TMJ) is the only bilateral linkage joint in the human body, exhibiting complex movement patterns that combine sliding and rotation, and plays an indispensable role in mandibular function [1]. Temporomandibular joint osteoarthritis (TMJOA) represents a critical subtype of TMJ disorders, pathologically characterized by synovial inflammation, cartilage degeneration, and * Corresponding author. ** Corresponding author.Department of Oral and Cranio-maxillofacial Surgery, Shangha

FAQs

Why do current treatments for TMJOA fail to stop disease progression?

Because they mainly provide symptomatic relief rather than targeting the underlying pathological mechanisms driving TMJOA progression.

How does Cur@M2-EVs affect mitochondrial-related processes in TMJOA?

Cur@M2-EVs attenuate inflammation and cartilage matrix degradation by scavenging reactive oxygen species, restoring mitochondrial membrane potential, and shifting cellular metabolism from glycolysis back to oxidative phosphorylation.

How are Cur@M2-EVs formulated for sustained release and improved joint lubrication?

They are further encapsulated within PEGDA hydrogel microspheres, forming the Cur@M2-EVs@PEGDA system for sustained drug release and enhanced lubrication.

Sep 30, 2026

Uploaded by Đào