Rational and Combinatorial Design of Biomaterials for Neural Engineering

Rensselaer Polytechnic Institute, Troy NY

Investigators

Abstract

1067208 Thompson Several 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).