Rational and Combinatorial Design of Biomaterials for Neural Engineering

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1067208ThompsonSeveral factors such as formation of scar tissue, inadequate removal of inhibitory myelin, cell death and lack of a permissive substrate or growth factors limit the ability of neurons to regenerate after an injury. The guiding rationale is that a tissue-specific biomaterial designed for both resident neural (sensory and motor neurons) and resident non-neural cells (Schwann cells and endothelial cells) of the peripheral nervous system combined with the appropriate soluble factors can serve as the foundation for a superior nerve guidance channel to address these challenges. Rational and combinatorial design strategies for the discovery of synergistic extracellular matrix proteins and soluble factors combinations generating a tissue-specific biomaterial for regenerating axons and support cells will be applied in a physiologically-relevant 3-dimensional environment. The objective is to systematically screen a large subset of matrix proteins, base scaffolds and soluble factors combinations to rationally design composite biomaterials for the peripheral nervous system. The long-term goal is to engineer a biomaterial for treatment of large-gap peripheral nerve injuries. Novel high throughput screening platforms, such as those proposed in this study, will accelerate the discovery of therapeutically relevant biomaterials for large-gap injuries of the peripheral nerve. This flexible platform can be further extended to screen for materials optimal for spinal cord injury, traumatic brain injury, and cell-based therapies for neurodegenerative diseases.Intellectual Merit: If successful, the proposed research will (1) develop a new framework to examine a prohibitively large experimental space for possible combinations of proteins, scaffolds and soluble factors that by conventional methods due to the time, effort and cost (2) identify cell-specific, novel biomaterial that will serve as a basis of a guidance channel to both promote neuronal growth and/or the migration/re-population of non-neuronal cells relevant to peripheral nerve injury, (3) translation of biomaterials relevant to large-gap peripheral nerve injury to injuries in the brain or spinal cord and (4) apply this high-throughput screening platform rationally generate biomaterial candidates for other target tissues of interest. Broader Impact: If successful, (1) the proposed research will develop a biomaterial to support nerve repair. (2) The research will include the participation of both high school students and undergraduate researchers. (3) Research findings will be broadly disseminated at national/regional meetings, manuscripts in peer-reviewed journals, and invited lectures. (4) Both Principal Investigators and graduate students funded by this project will volunteer by presenting short workshops broadly based on neural engineering to encourage K-12 interest in the Science, Technology, Engineering and Medicine (STEM fields).