Extracellular Vesicles Functional “Brick‐Cement” Bio‐Integrated System for Annulus Fibrosus Repair

Abstract Due to the deficiency of mechanical supporting after discectomy and weak proliferative capacity of annulus fibrosus (AF) cells, the AF defect repair remains a clinical challenge. Herein, a myofibroblasts derived extracellular vesicles (M‐EVs) functional “brick‐cement” bio‐integrated system (M‐EVs@PGBgel) is developed to repair AF defect. The modified Poly(glycerol‐sebacate) (PGBS), “bio‐brick” layer, exhibited excellent support features on account of its elastomeric mechanical properties. The loaded M‐EVs in the “bio‐cement” layer activated ITGA6/PI3K/AKT pathway, regulated M2 macrophage polarization, thus synergistically promoting AF cell proliferation and migration. The “bio‐cement” layer integrated PGBS and remnant tissue at the defect through the Schiff base reaction and aided M‐EVs’ sustained release. This study demonstrated that M‐EVs@PGBgel significantly improved the disc's biological and mechanical properties in the AF defect microenvironments and promoted AF regeneration in vivo. The M‐EVs@PGBgel shows promise as an effective strategy to simultaneously address the mechanical imbalance and biological disruptions resulting from AF defect.