Thermo-responsive shape memory biomaterials with structural and physical adaptivity for scarless personalized nerve repair

Nerve guidance conduits (NGCs) have emerged as promising alternatives to autologous nerve grafts for peripheral nerve repair, overcoming donor site morbidity while promoting axonal regeneration. However, size and structure mismatch in conventional NGCs impairs axon sprouting, remyelination and neural regeneration efficacy. Here, we engineered a thermo-responsive self-rolling multichannel NGC comprising shape-memory poly (lactide-co-trimethylene carbonate) (PLMC), silk fibroin (SF), and reduced graphene oxide (rGO) to enable scarless regeneration with personalized anatomical matching. The electrospun PLMC/SF-rGO conduit features axially aligned inner fibers providing topographical guidance cues for directional guidance and exhibits programmable shape recovery, enabling intraoperative customization and shape resistance throughout the nerve regeneration period. In vitro, 0.5 % rGO optimally enhanced Schwann cell migration, proliferation and neuronal proliferation. In vivo assessment in rat 10-mm sciatic defects over 12 weeks demonstrated that PLMC/SF-rGO NGCs significantly outperformed PLMC/SF controls in functional recovery, reduced muscle atrophy, and decreased fibrosis. Histology further confirmed superior axonal regeneration and marker expression (NF200/S100β), achieving outcomes comparable to autografts. This multichannel NGC synergizes structural and physical adaptability, electrical conductivity, and bioactive cues to accelerate nerve regeneration, offering a promising alternative to autografts for scarless personalized repair.