末梢神経再生のためのNDP-MSH負荷自己組織化ペプチドヒドロゲルで機能化された生分解性ポリウレタン神経導管

Autologous nerve grafting remains the clinical gold standard for segmental peripheral nerve repair, but it is limited by donor-site morbidity and graft availability. Nerve guidance conduits (NGCs) offer a promising alternative for peripheral nerve repair. In this work, we engineered a fully biodegradable waterborne polyurethane (BWPU) NGC functionalized with a pH-responsive self-assembling peptide (SAP) loaded with [Nle4, D-Phe7]-α-melanocyte-stimulating hormone (NDP-MSH)-an α-MSH analogue that activates melanocortin receptors and has been reported to attenuate oxidative stress, apoptosis, and neuroinflammation. BWPU (17 mol% PEG) was fabricated into porous conduits and integrated with NDP-MSH-loaded SAP to provide mechanical support for peripheral nerve repair while enabling controlled peptide release, thereby coupling structural support with antioxidant/pro-survival signaling. In vitro, NDP-MSH at appropriate concentrations attenuated oxidative damage in RSC96 Schwann cells by reducing intracellular reactive oxygen species (ROS) and LDH release. In vivo, 10-mm rat sciatic nerve defects were bridged with BWPU, SAP@BWPU, NDP-MSH@SAP@BWPU conduits, or Autograft. Early post-implantation, NDP-MSH@SAP@BWPU reduced apoptosis and promoted an M2-enriched immune microenvironment. At 60 days post-repair, the NDP-MSH@SAP@BWPU group achieved structural, functional, and electrophysiological outcomes comparable to the Autograft group. These findings demonstrate that NDP-MSH delivery via a BWPU-SAP depot-enabled conduit is an effective strategy to biofunctionalize biodegradable NGCs and may offer a viable alternative to autografts for peripheral nerve repair.