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

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.