Laponite Network Controls FGF‐2 Release and Drives Functional Nerve Regeneration via 3D‐Printed Nerve Wrap Interfaces

ABSTRACT Peripheral nerve transection requires surgical treatment, although functional recovery remains incomplete. Here, we developed a biofunctional nanocomposite nerve interface combining an ion‐covalent gelatin methacryloyl (GelMA)/Laponite hydrogel with engineered thermostable fibroblast growth factor‐2 (FGF‐2) to recreate a regenerative microenvironment. Laponite incorporation (2%–2.5% w/v) precisely modulated the hydrogel network, providing shear‐thinning behavior, enhanced viscoelasticity, microporosity, a twofold increase in compressive modulus, controlled degradation, injectability, and three‐dimensional (3D) bioprintability. Functionalization with thermostable FGF‐2 enabled sustained release while preserving bioactivity, promoting Schwann cell viability, metabolic activity, cytoskeletal organization, and upregulation of nerve growth factor receptor (NGFR), glial cell line‐derived neurotrophic factor (GDNF), early growth response protein 2 (EGR2), octamer‐binding transcription factor 6 (OCT6), and SRY‐box transcription factor 9 (SOX9). Nerve interfaces consisting of a basal polycaprolactone (PCL) layer and a biofunctional GelMA (10%)/Laponite (2%) hydrogel containing FGF‐2 (1 µg mL − 1 ) were fabricated by 3D bioprinting followed by visible‐light crosslinking. In a rat neurotmesis model, FGF‐2‐functionalized wraps significantly improved motor function, electrophysiological recovery, Schwann cell activity (S100 calcium‐binding protein), neurofilament organization and myelination (FluoroMyelin), and muscle preservation. Collectively, this work introduces a 3D‐bioprinted, cell‐instructive nerve interface integrating mechanical neuroprotection with sustained neurotrophic signaling to enhance peripheral nerve regeneration.