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

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.