Biomimetic Multilayered Gas‐Foaming Scaffold with Sustained bFGF Delivery for Annulus Fibrosus Regeneration

Abstract Current clinical treatments for intervertebral disc (IVD) herniation (e.g., discectomy) often lead to re‐herniation, and tissue engineering scaffolds for annulus fibrosus (AF) regeneration remain scarce, particularly those capable of mimicking the multilayered structure of native AF. This study combines electrospinning with gas‐foaming technology to fabricate a 3D nanofiber scaffold (3DS) with a hierarchical multilayered structure. Subsequently, fibronectin is employed as a “bridge” to immobilize basic fibroblast growth factor (bFGF) onto 3DS through its inherent gelatin and heparin binding domains, ultimately constructing a 3D bioactive AF scaffold (3DFF). In vitro experiments demonstrate that the 3DFF mimicks the multilayered structure of native AF. Through sustained bFGF release, it enhances extracellular signal‐regulated kinase (ERK) phosphorylation and activates the Wnt/β‐catenin pathway, thereby promoting cell proliferation, migration, and matrix secretion. In vivo experiments using a rat tail AF defect model show that 3DFF mitigates IVD degeneration and facilitates AF regeneration. In summary, this study develops a bioactive biomimetic multilayered annulus fibrosus scaffold, offering a promising strategy for annulus fibrosus repair following discectomy.