Dual-loaded BMSCs–Metformin microgels promote cartilage repair through combined anti-inflammatory, antioxidant, and regenerative effects

Li D, Wang Y, et al.

Biomaterials

Zhejiang University School of Medicine, Guangxi University of Chinese Medicine, Dalian Medical University, Central South University, Wenzhou Medical University

China

RESEARCH SUMMARY

This study developed a multifunctional injectable microgel system (BMSC-Met@MGs) combining bone marrow mesenchymal stem cells (BMSCs) and metformin within a GelMA/CSMA/PVA matrix fabricated via microfluidics. The microgels provide simultaneous anti-inflammatory, antioxidant, and regenerative functions for articular cartilage repair. In vitro, BMSC-Met@MGs suppressed MMP3/MMP13 expression, reduced ROS accumulation, restored mitochondrial potential, and promoted chondrogenic differentiation through COL2A1 and ACAN upregulation. In vivo rat models demonstrated hyaline cartilage regeneration and subchondral bone restoration comparable to native cartilage. The system integrates biochemical, pharmacologic, and mechanical cues to address the oxidative stress and inflammation microenvironment after injury, offering a comprehensive approach to osteochondral regeneration.

Mechanical compression testing of GelMA/CSMA/PVA microgels and Met@MGs was performed using a CellScale MicroTester G2 (Waterloo, Canada). Samples (n=4) were tested under uniaxial compression to measure stress–strain behavior and determine effective Young’s modulus. The addition of metformin slightly reduced stiffness (3.38 ± 0.41 kPa for MGs vs. 2.87 ± 0.51 kPa for Met@MGs), attributed to hydrogen bonding that lowered polymer crosslinking density. Testing in PBS simulated physiological conditions, confirming the microgels’ mechanical resilience and injectability through an 18-gauge needle. The MicroTester G2 data established the tunable mechanical properties essential for mimicking native cartilage elasticity and supporting BMSC proliferation.

AUTHORS

Danmei Li, Yixiang Wang, Guangxun Yuan, Feifei Zhou, Hongpu He, Xiangyu Du, Shuyu Liu, Wentao Gao, Xuxuan Fan, Zhiqin Liu, Binbin Ma, Zhenhan Deng, Shuai Li, Jian Xu.

PUBLICATION DETAILS

JOURNAL

Biomaterials

YEAR

2025

INSTITUTIONS

Zhejiang University School of Medicine, Guangxi University of Chinese Medicine, Dalian Medical University, Central South University, Wenzhou Medical University

COUNTRIES

China

INSTRUMENT USED

MicroTester

TESTING METHODS

Compression TestingHydrated and Temperature Controlled TestingMicro-Mechanical Testing

RESEARCH APPLICATIONS

Cartilage and Meniscus MechanicsCell Laden HydrogelsFibrosis & Tissue RemodelingHydrogel Mechanical TestingInjectable & Regenerative BiomaterialsStem Cell Mechanobiology

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