No cure is available for the enduring deficits induced by traumatic brain because neurons within the central nervous system do not spontaneously regenerate. Implantation of artificial biosynthetic scaffolds provides a favorable microenvironment for residual neuron protection and regeneration. Artificial scaffolds mimicking the extracellular matrix can be modified to promote cell adhesion, signaling and growth for injured brain repair. Here, we propose a novel neural regeneration treatment by conjugation of neural mimics to self-assembling multi-domain peptide (MDP). MDP self-assemble into anti-parallel β-sheets in deionized water, which further entangle into fibrous meshes when crosslinked by multivalent ions such as phosphate in phosphate buffered saline (PBS). These highly hydrated meshes have been shown to generate nanofibrous hydrogels that shear thin and recover, and can therefore be easily syringe aspirated and injected in situ. The base sequence of MDP is termed SL (K2(SL)6K2). We have shown previously that MDP can be easily modified with functional peptide sequences and tuned to promote cell adhesion and proliferation. In this study, three different short peptide sequences will be conjugated to SL: peptide mimic 1, peptide mimic 2 and peptide mimic 3. Peptide mimic 1 is a laminin mimic for neural extracellular matrix promoting neural development and survival; peptide mimic 2 and 3 are Mimics for Neurotrophin (NT), a family of growth factors including nerve growth factor and brain-derived neurotrophic factor. NT induces the survival, development, and function of neurons. The peptides are being synthesized and hydrogel will be characterized for rheology and circular dichroism. The ability of these modified MDP hydrogel to promote neuron survival and regeneration by providing a sustained favorable microenvironment will be tested in vitro on SH-SY5Y cell line and in vivo through depositing on lesion at a traumatic brain injury model on rats. MTS, FACS and immunohistology will be employed for cell and implant samples.

Neuroprotective multi-domain peptide hydrogel in traumatic brain injury

251st National Meeting (2016)

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