Biomimetic design of peripheral nerve guides

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This award by the Biomaterials program in the Division of Materials Research to University of Pittsburgh is to combine engineering innovations (interfacial processes driven by thermodynamic intermolecular forces), breakthroughs in protein transport, and recent insights on neurovascular cross talks to create nerve guides that can induce co-regeneration of neurovascular systems. This award is cofounded by the Interfacial Processes and Thermodynamics program in the Division of Chemical, Bioengineering, Environmental, and Transport Systems. Peripheral nerve system regeneration is still a significant challenge because majority of these patients have limited functional recovery. The presently used autografts cause donor site morbidity. Rationally-designed biomaterial nerve guides with aligned microchannels proposed in this project would avoid donor site morbidity and may offer functional recovery. Vascular transport is critical to sustain regenerating axons, and yet this aspect is at present overlooked in nerve regeneration treatments. The innovation of this research is in the unique presentation of contact guidance and transport of growth factors to the cells. The proposed guide will have a completely open porous structure that enhances mass transfer while providing directed cell growth along the guidance channels. The proposed guide will use biomimetic transport of growth factors to induce co-regeneration of the neurovascular systems. The intellectual merit of this research is in: 1) the preparation of electrospun nerve 3D guides with parallel microchannels and microfibers prepared from polycaprolactone and gelatin at different ratios. This versatile platform will incorporate contact guidance and biochemical cues using innovative designs; and 2) the proposed innovative design of the nerve guide that will enhance the regeneration of central nerve system because many central nerve tracks have long parallel axon bundles within the track. The described research would generate a versatile platform for a new approach to nerve guides. The innovative nerve guide design will also impact research for the guided regeneration of other tissues such as cardiovascular regeneration, where nerve control of engineered cardiovascular tissues is largely unexplored at present. This project will be integrated into this researcher's educational activities of students. The graduate and undergraduate students will benefit from rigorous interdisciplinary training in this cutting edge research at the interface of materials science, biochemistry, and neurobiology. Furthermore, the research team will disseminate this research to the scientific community through high impact journals. Additionally, the investigator plans to inform the general public about the research activities by news releases, social media and internet.Peripheral nerve injury is a very stressful and physically debilitating injury, and presents a significant societal and economic burden. The current clinical approach is by harvesting a donor nerve from one site of the body and transplanting it to the injury site. This presents a multitude of problems including losing nerve functions at the donor site, and size mismatch of the graft and the injured nerve. The goal of this research is to create man-made nerve guides that promote peripheral regeneration of nerve. The nerve-guide design is based on thorough examinations of how healthy nerve functions and how injured nerve degenerate after injury. Students working on this research will be trained in a cross-disciplinary environment exploring the frontiers of regenerative medicine. This will prepare them to become leaders of the next generation researchers in neural studies. More broadly, the highly translational nature of this project means that when successfully completed, patients suffering from peripheral nerve injuries will benefit from improved functional recovery without loss of nerve function at the donor site. The investigator is very active in outreach activities such as recruiting minority students into research programs, and mentoring and hosting high school research teams. The research activities will be disseminated to broadest possible audience through biweekly blogs through internet and social media.