Peripheral nerve injury is a major clinical challenge that often results in incomplete functional recovery. Although nerve growth factor is a promising therapeutic molecule for nerve repair, its clinical application is limited by the high cost of recombinant protein production and the burst release associated with conventional post-loading delivery strategies. In this study, we developed an integrated design strategy termed source functionalization. Transgenic silkworms were generated to express recombinant human nerve growth factor in the silk gland under the control of the fibroin heavy chain promoter. This enabled the co-production of recombinant human nerve growth factor with endogenous silk fibroin and its physical entrapment within the fibroin matrix, allowing sustained release. Direct processing of these glands yielded an intrinsically functionalized injectable hydrogel, avoiding complex purification and reconstitution steps. In vitro , the hydrogel promoted neuronal proliferation and differentiation. In a rat sciatic nerve crush model, it significantly improved functional recovery and enhanced axonal regeneration and remyelination. These results demonstrate a cost-effective and scalable one-step strategy for preparing bioactive silk-based materials for peripheral nerve repair.
Wu et al. (Tue,) studied this question.