Extracellular matrix-inspired biomimetic construction by IKVAV-functionalized ovalbumin hydrogel for regulating Schwann cells and DRG growth in nerve regeneration.

Peripheral nerve injury repair remains a prominent clinical challenge owing to the limited self-regenerative capacity of neural tissues and the lack of ideal biomimetic microenvironmental scaffolds. Hydrogels can mimic the extracellular matrix but commonly lack specific bioactive signals to efficiently drive neural regeneration. To address this issue, we developed an IKVAV (Isoleucine-Lysine-Valine-Alanine-Valine) peptide-functionalized ovalbumin (OVA) hydrogel via chemical crosslinking and dopamine-mediated surface modification. Physicochemical characterizations demonstrated that the hydrogel possessed favorable gelation efficiency, tunable viscoelasticity, suitable mechanical strength, good hydrophilicity, and controllable swelling and degradation behaviors. Fourier transform infrared spectroscopy verified the successful immobilization of IKVAV peptides on the OVA hydrogel. In vitro cellular evaluations revealed that compared with pure OVA hydrogel, the IKVAV-functionalized hydrogel significantly improved the adhesion, proliferation, migration, and morphological elongation of Schwann cells (RSC96), and markedly promoted axonal growth and directional extension of dorsal root ganglion (DRG) neurons. Mechanistic studies using quantitative PCR and proteomic analysis confirmed that the functional scaffold significantly upregulated the expression of genes and proteins related to cell survival, axonal extension, myelination, and angiogenesis, possibly through activating the IKVAV-integrin-YAP (Yes-associated protein) signaling axis. These results indicate that the IKVAV-functionalized OVA hydrogel constructs a biomimetic neural regenerative microenvironment by integrating physical support and biological cues, thereby synergistically enhancing Schwann cell activity and axonal regeneration. This study provides a novel multifunctional hydrogel strategy for peripheral nerve tissue engineering and injury repair.