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Peter Nguyen1 Patricia Iglesias-Montoro1 Biplab Sarkar1 Vivek Kumar1

1, New Jersey Institute of Technology, Newark, New Jersey, United States

Over 10 million people worldwide suffer from strokes each year. For the more than 42 million people around the world who have survived a stroke, their quality of life is often greatly diminished due to varying degrees of brain damage. Many of the survivors of stroke often suffer from some loss of sensory and motor function, including altered hearing and vision, abnormal gait, speech complications, and paralysis. Brain injury recovery primarily focuses on physical rehabilitation; there is currently no FDA approved neuroprotective and regenerative therapy to mute disability or to help improve original quality of life. Nerve growth factor (NGF) and brain-derived neurotropic factor (BDNF) have shown to be neuroprotective in a rat middle cerebral artery occlusion (MCAO) model. However, delivery of these growth factors to the target area requires the ability to cross the blood-brain barrier and substantial dosing to elicit any positive outcome. This issue can be overcome by an injectable delivery system that can provide a more sustained release profile. We describe a method for the development of an injectable peptide-based hydrogel delivery system that incorporates a neurogenic peptide. This drug delivery system is thixotropic (shear thinning) and biodegradable, allowing the biomaterial to flow to the target site and form a hydrogel in situ to provide sustained neurogenic peptide release. The prolonged release of the neurogenic peptide from the hydrogel can provide a neuroprotective effect following stroke and create a suitable environment for neuroregeneration. This technology platform is centered on the formation of antiparallel β-sheets, using noncovalent interactions, to allow the peptides to crosslink together to form hydrogels. Peptides can be incorporated with mimics of biological factors, presented at high epitope density during supramolecular assembly, overcoming drawbacks typical of standard growth factor delivery. The self-assembling peptide hydrogels were tested for their biocompatibility through in vitro cell culture and in vivo subcutaneous injection in mice, respectively. Their potential to provide neuroprotection and regeneration was also optimized in vitro with neurons before moving to an in vivo MCAO rat model. This proposed research aims to bridge the gap between disease management and post-stroke recovery in an attempt to restore bodily activities and improve the quality of life of stroke victims. The success of this drug delivery system may also prove efficacious for restoring perfusion and vitality to damaged brain tissue after traumatic injury.

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