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<p>This study aimed to develop a KeMA hydrogel encapsulating cartilage-affinity peptide (CAP)-modified extracellular vesicles (EVs) derived from MEF2C-overexpressing macrophages (KeMA@CAP-EVs-MEF2C) to modulate the MEF2C/P21/CDK2 axis, attenuating inflammation in cartilaginous endplate chondrocytes (CEPCs) and cellular senescence in nucleus pulposus cells (NPCs) to slow intervertebral disc degeneration (IVDD) progression. Single-cell RNA sequencing (scRNA-seq) identified MEF2C as a key regulator, upregulating p21 and suppressing CDK2 to reduce inflammation and cellular senescence. CAP-modified EVs within KeMA hydrogel demonstrated enhanced delivery and sustained-release properties. In vivo validation showed effective mitigation of cellular senescence and structural restoration in IVDD. This biomimetic system offers a promising strategy for IVDD treatment, emphasizing its targeting efficiency, biocompatibility, and sustained therapeutic benefits.</p> Graphical abstract <p></p>

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Biomimetic KeMA hydrogel encapsulating CAP-EVs-MEF2C for inhibiting inflammation and senescence in intervertebral disc degeneration

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月17日

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  • Jian-Bin Guan,
  • Kai-Yuan Lin,
  • Shan-Xi Wang,
  • Ying-Guang Wang,
  • Ling-Jiang Li,
  • Ren-Ji Wang,
  • Peng Zou,
  • Xiao-Fan Bai,
  • Si-Bo Wang,
  • Liang Yan,
  • Yuan-Ting Zhao,
  • Xiao-Jun Yu

摘要

This study aimed to develop a KeMA hydrogel encapsulating cartilage-affinity peptide (CAP)-modified extracellular vesicles (EVs) derived from MEF2C-overexpressing macrophages (KeMA@CAP-EVs-MEF2C) to modulate the MEF2C/P21/CDK2 axis, attenuating inflammation in cartilaginous endplate chondrocytes (CEPCs) and cellular senescence in nucleus pulposus cells (NPCs) to slow intervertebral disc degeneration (IVDD) progression. Single-cell RNA sequencing (scRNA-seq) identified MEF2C as a key regulator, upregulating p21 and suppressing CDK2 to reduce inflammation and cellular senescence. CAP-modified EVs within KeMA hydrogel demonstrated enhanced delivery and sustained-release properties. In vivo validation showed effective mitigation of cellular senescence and structural restoration in IVDD. This biomimetic system offers a promising strategy for IVDD treatment, emphasizing its targeting efficiency, biocompatibility, and sustained therapeutic benefits.

Graphical abstract