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

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.