(53c) Enhanced In Vivo Neuronal Survival after Traumatic Brain Injury Facilitated By an Injectable Self-Assembled Peptide Hydrogel
AIChE Annual Meeting
2019
2019 AIChE Annual Meeting
Materials Engineering and Sciences Division
Biomaterials and Life Science Engineering: Faculty Candidates II
Monday, November 11, 2019 - 8:36am to 8:54am
The self-assembling peptide was designed with a central fibrillizing domain and a terminal neuroprotective domain. Upon solvation in an aqueous buffer containing multivalent counter-ions, the peptide strands self-assemble to form a nanofibrous hydrogel. The neuroprotective domain is immobilized in the peptide primary structure and thus can provide sustained in vivo efficacy without rapid diffusion. The non-covalent interactions involved in the self-assembly of the peptide are reversible, and thus the hydrogel can undergo shear-thinning during injection and regain its storage modulus post-implantation. The putative neuroprotective effects of SLen was examined both in vitro in primary cortical neuron culture after glutamate-mediated excitotoxicity and in vivo after lateral fluid percussion injury (FPI) in 8-week-old male Sprague Dawley rats. In the latter case, SLen hydrogel was injected right after FPI directly into the impacted site on the cortex, without surgery. Controls included sham and injury with saline injection. Neuronal survival was evaluated at day 7 post-TBI, by immunostaining of neuronal cell bodies and axonal projections.
SLen nanofibers are neuroprotective and promote neuronal survival growth after injury both in vitro and in vivo. The nanofibrous matrix offers a facile microenvironment for neuronal survival, arresting acute excitotoxic outcomes. Next, we will focus on the biodistribution of the peptides and fine-tuning of the material properties of the hydrogel to optimize neuronal support.