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Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury.


ABSTRACT: The signaling of cells by scaffolds of synthetic molecules that mimic proteins is known to be effective in the regeneration of tissues. Here, we describe peptide amphiphile supramolecular polymers containing two distinct signals and test them in a mouse model of severe spinal cord injury. One signal activates the transmembrane receptor β1-integrin and a second one activates the basic fibroblast growth factor 2 receptor. By mutating the peptide sequence of the amphiphilic monomers in nonbioactive domains, we intensified the motions of molecules within scaffold fibrils. This resulted in notable differences in vascular growth, axonal regeneration, myelination, survival of motor neurons, reduced gliosis, and functional recovery. We hypothesize that the signaling of cells by ensembles of molecules could be optimized by tuning their internal motions.

SUBMITTER: Alvarez Z 

PROVIDER: S-EPMC8723833 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury.

Álvarez Z Z   Kolberg-Edelbrock A N AN   Sasselli I R IR   Ortega J A JA   Qiu R R   Syrgiannis Z Z   Mirau P A PA   Chen F F   Chin S M SM   Weigand S S   Kiskinis E E   Stupp S I SI  

Science (New York, N.Y.) 20211111 6569


The signaling of cells by scaffolds of synthetic molecules that mimic proteins is known to be effective in the regeneration of tissues. Here, we describe peptide amphiphile supramolecular polymers containing two distinct signals and test them in a mouse model of severe spinal cord injury. One signal activates the transmembrane receptor β1-integrin and a second one activates the basic fibroblast growth factor 2 receptor. By mutating the peptide sequence of the amphiphilic monomers in nonbioactive  ...[more]

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