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Biomimetic KeMA hydrogel encapsulating CAP-EVs-MEF2C for inhibiting inflammation and senescence in intervertebral
Jian-Bin Guan1,2, Kai-Yuan Lin1,2, Shan-Xi Wang1,2
1Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Shaanxi Key Laboratory of Spine Bionic Treatment, No.555 Youyi East Road, South Gate, Beilin District, Shaanxi, 710054, Xi'an, China.
Abstract:
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.
