02263nas a2200421   4500000000100000000000100001008004100002260001500043653001700058653001600075653002600091653002800117653002300145100001800168700001400186700001900200700001400219700002300233700001400256700002300270700002900293700002100322700002200343700001800365700001400383700001700397700001500414700002700429700001700456700001500473700001900488700002000507245005500527856005500582300000900637520118100646022001401827       2026                            d  c2026-02-1110abiomaterials10aBiomimetics10aRegenerative Medicine10aStem-cell biotechnology10aTissue engineering1 aNozomu Takata1 aZhiwei Li1 aAnna Metlushko1 aFeng Chen1 aNicholas A. Sather1 aXinyi Lin1 aMatthew J. Schipma1 aOscar A. Carballo-Molina1 aCassandre Jamroz1 aMadison E. Strong1 aCara S. Smith1 aYang Yang1 aChing M. Wai1 aNeha Joshi1 aJack Kolberg-Edelbrock1 aKyle J. Gray1 aSuitu Wang1 aLiam C. Palmer1 aSamuel I. Stupp00aInjury and therapy in a human spinal cord organoid  uhttps://www.nature.com/articles/s41551-025-01606-2  a1-143 aDamage to the spinal cord can lead to irreversible paralysis and loss of sensory function, but translation of preclinical therapies remains elusive. We recently showed that bioactive supramolecular assemblies of peptide amphiphiles can reverse paralysis in an acute mouse model following severe spinal cord injury (SCI). Here we report the development of two human spinal cord organoid injury models to simulate SCI in vitro, a laceration of the organoid with a scalpel and a compressive contusion commonly used in preclinical models, both resulting in immediate neuronal death and the formation of glial scar-like tissue. Treatment of the injured organoids with the preclinical therapy suppressed the scar-like tissue and promoted significant axonal regeneration, as observed previously in vivo. With the inclusion of microglia into the spinal cord organoids, we demonstrate that the supramolecular nanomaterial reduced pro-inflammatory factors commonly associated with injury. The human spinal cord organoid models developed here could accelerate the discovery of therapies to treat SCI and possibly damage of other central nervous system tissues owing to trauma or disease.  a2157-846X