Rapid 3D-printing of Multi-functional Adaptive Nerve Conduits

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Rapid 3D-printing of Multi-functional Adaptive Nerve Conduits The PIs propose to develop an innovative platform for the fabrication of 3-dimensional (3D) nerve conduits with precise spatial and temporal distribution of biological factors (growth factors, neuron stem cells and extracellular matrix (ECM)). This rapid 3D printing platform employs a dynamic mask for photopolymerization of an entire layer simultaneously without scanning and create 3D conduits continuously, resulting in 1,000 times faster in printing speed and 100 times better in printing resolution compared to traditional nozzle-based 3D printers. Hyaluronic acid (HA), an ECM component, will be modified for 3D printing. HA is a long-chain sugar-like molecule shown to be compatible with wound healing and nerve regeneration. Because it is naturally occurring in the body and has negligible inter-species variation, HA is an excellent candidate biomaterial to use for nerve conduits. Neuron stem cells and growth factors will be printed in the conduits to aid nerve repair. In the R21 phase, the PIs will develop the rapid 3D printing system, synthesize the HA materials and characterize the 3D printed HA conduits. The team will then implement these nerve conduits into mice to demonstrate growth of the nerve fibers along the bore of the conduit from proximal to distal end and also demonstrate reduction in time to functional recovery due to conduit-assisted growth and regeneration of the nerve fiber. Upon successful completion of these tasks and milestones in the R21 phase, subsequent work in the R33 phase will further develop the rapid 3D printing process to create "designer" nerve conduits with precise spatio-temporal control of physical, chemical, and biological properties and use such designer conduits for in vivo animal studies. The concepts and techniques developed herein would allow us to create precise, pre-designed distributions of growth factors and neuron stem cells with microscale resolution and enable us to investigate their effects on nerve cell guidance inside a conduit with complex architectures. The project will be carried out by a team of collaborative talents, including Dr. Chen who is a leading expert in 3D printing and a pioneer in bioprinting, and Dr. Nguyen who is a is board certified in both Head and Neck Surgery and Neurotology/Skull Base Surgery and is the Director of the Facial Nerve Clinic at UC San Diego. Dr. Nguyen has a clinical practice specializing in facial nerve paralysis and brings both clinical expertise as well as basic science research experience to this project.