An engineered graft to encourage preferential motor reinnervation following perip

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DESCRIPTION (provided by applicant): Biotechnology to enhance regeneration of significant lengths of peripheral nerve (PN) and subsequent functional recovery remains a critical need. Patients with uncorrectable nerve injuries face permanent loss of motor control and/or sensation. Although PNs are intrinsically capable of regeneration, they can only do so unaided across small gaps. Grafting of autologous nerve remains the best option, but donor morbidity and supply limitations remain problematic. Synthetic conduits have entered the market but have been ineffective for large gaps. This Bioengineering Partnership aims to combine the biological benefits of the inherent regeneration process through use of mimics of natural growth enhancers with the off-the-shelf convenience of a synthetic conduit with superior chemical and mechanical properties. Three laboratories at Rutgers University have established an interdisciplinary collaboration to jointly address major hurdles for a peripheral regeneration device for repair of large gaps. Dr. Melitta Schachner has identified several novel compounds that enhance not only the speed of PNR, but improve the quality of nerve regeneration by preferentially targeting regenerating motoneurons to muscle. Dr. David Shreiber has developed innovative methods to graft and pattern these enhancers to clinically relevant hydrogels used as conduit fillers, increasing the duration of activity and providing spatial guidance. Lastly, Dr. Joachim Kohn has combined novel co- polymer design with advanced manufacturing approaches to develop biodegradable polymer conduits with the flexibility necessary for large gaps that are additionally capable of eluting the bioactive compounds in a controlled fashion. The research team proposes to (i) develop a versatile platform of degradable conduits with tunable degradation and controlled release profiles; and optimize (ii) the spatial presentation of immobilized enhancers on a supporting scaffold within the conduits, (iii) the temporal presentation of soluble enhancers released from the conduits, and (iv) test the efficacy of the device in a large-gap animal model. By establishing a close research partnership, the applying laboratories will not only avoid the pitfall of creating components that are mutually exclusive or marginally compatible, but will realize an advanced time frame to develop the best possible combination of these three components to enhance the speed and quality of PN regeneration.