The trauma caused by brain injury can lead to a pathologic cascade resulting in local inflammation and neuronal death. Current tissue engineering approaches have focused on developing implantable biomaterials that can stem the pathologic sequelae and aid in tissue regeneration in vivo. However, intricate surgical procedures involved in the implantation limit the potential of the therapeutic route. We report an injectable peptide-based hydrogel that can be injected intracranially in a non-invasive fashion into the injury site and demonstrate marked improvement in neuronal survival. The self-assembly of the peptide into nanofibers is mediated by non-covalent interactions among the peptide strands (hydrogen bonds, hydrophobic interaction, van der Waals interaction), and the nanofibers are ionically cross-linked into the bulk hydrogel. These underlying non-covalent bonds render the hydrogel sensitive to shear-thinning, however they can regain their elasticity almost immediately after a shearing event. Thus, the therapeutic hydrogel can be easily syringe-aspirated and injected directly into the brain injury site. The peptide nanofibers were functionalized with a neuroprotective domain (ependymin mimic sequence) and have shown efficacy in an in vitro cortical neuron model. We used a fluid percussion injury (FPI) model in rodents and injected our beta-sheet-based nanofibrous hydrogels in situ, after the injury. We demonstrated therapeutic efficacy of the injected hydrogel through immunohistochemistry (VWF, alpha-SMA, NeuN, and myelin basic protein). Injectable peptide-based biomaterials may prove to be excellent tools to arrest and even reverse some of the pathological sequences after a traumatic brain injury.

Injectable neuroprotective peptide hydrogels

2019 Fall National Meeting

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