Gastrodin modified polyurethane conduit promotes nerve repair via optimizing Schwann cells function

Peripheral nerve regeneration and functional recovery remain a major clinical challenge.Nerve guidance conduit(NGC)that can regulate biological behavior of Schwann cells(SCs)and facilitate axonal regeneration through microenvironmental remodeling is beneficial for nerve regeneration and functional recovery.Gastrodin,a main constituent of a Chinese traditional herbal medicine,has been known to display several biological and pharmacological properties,especially antioxidative,anti-inflammatory and nerve regeneration.Herein,polyurethane(PU)NGCs modified by different weight ratio of Gastrodin(0,1 and 5 wt%)were designed for sequential and sustainable drug release,that created a favorable microenvironment for nerve regeneration.The scaffold showed suitable pore structure and biocompatibility in vitro,and evidently promoted morphological and functional recovery of regenerated sciatic nerves in vivo.Compared to the PU and 1% Gastrodin/PU scaffolds,the 5% Gastrodin/PU significantly enhanced the proliferation,migration and myelination of SCs and up-regulated expression of neurotrophic factors,as well as induction of the differentiation of PC12 cells.Interestingly,the obvious anti-inflammatory response was observed in 5% Gastrodin/PU by reduced expression of TNF-α and iNOS,which also evidenced by the few fibrous capsule formation in the subcutaneous implantation.Such a construct presented a similarity to autograft in vivo repairing a 10 mm sciatic nerve defects.It was able to not only boost the regenerated area of nerve and microvascular network,but also facilitate functional axons growth and remyelination,leading to highly improved functional restoration.These findings demonstrate that the 5% Gastrodin/PU NGC efficiently promotes nerve regeneration,indicating their potential for use in peripheral nerve regeneration applications.