Multi-functional Polymer Structures for Promoting Neurite Extension and Myelination

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Non-Technical: Each year in the U.S., several million people suffer from peripheral nerve injuries that occur with accidental trauma or during the course of surgery. Failure to restore damaged nerves leads to the loss of muscle function, impaired sensation, and painful neuropathies. Autologous nerve graft, the "gold standard" in surgery, has disadvantages such as limited source, additional surgery, and mismatch between injured nerve and donor nerve. Synthetic nerve conduits are thus needed for bridging the long gap between injured peripheral nerve stumps. Polymers used for fabricating suitable nerve conduits should have capability of resisting tear, suturability, and ease of incorporation with support cells and nerve growth factor (NGF). There only exist a few crosslinkable and biodegradable ones for microfabrication of nerve conduits and it is largely unknown how to achieve optimal material environment to maximize neuronal and glial cell functions and axonal growth. The PI proposes an innovative and unique solution to manufacture biodegradable polymer nerve conduits with complex multi-component structures and multiple functionalities. By performing comprehensive, systematic studies using a wide range of physicochemical and structural characteristics of polymers, the PI will achieve both fundamental understanding and practically useful medical devices for fostering the synergistic transfer of know-how among research communities of materials, biomedical engineering, and medicine.Technical: The PI proposes to integrate photo-reactive, biodegradable polymers synthesized from poly(ethylene glycol), poly(epsilon-caprolactone), and poly(L-lysine), and bioactive reagents (e.g., NGF and cell-adhesive peptides), via solvent-free processes into multi-component, multi-functional structures with a wide range of physicochemical properties and structural features for promoting peripheral nerve repair. Using these polymer structures, the PI proposes to achieve fundamental understanding how polymer physicochemical properties regulate the behaviors and functions of both neuronal (e.g., dorsal root ganglion neurons) and glial cells (e.g., conditionally immortalized Schwann cell precursor line cells), and then optimized to maximize neurite extension and myelination. As well as the materials and processing parameters, the optimized polymer structures will guide more precise micro-fabrication of nerve conduits, and their in vivo animal implantation and histological analysis. The proposed fabrication method and drug delivery systems can also be applied to other tissue engineering applications. The PI proposes to provide an open access of scaffolding and cell regulation; curriculum on Biomaterials Fabrication and Processing; summer research experience for undergraduates, minorities, and underrepresented groups; disseminate discoveries to K-12 students through outreach programs; and develop lab/course modules for public high-school teachers and students through Pre-collegiate Research Scholars Program and distance education.