A novel biodegradable nerve conduit drug delivery device for peripheral nerverepair

Project Summary Nerve injury can occur due to traumachronic compression or disease processes such as diabetes or tumors and have a tremendous socioeconomic impact from loss of work and healthcare costsThere is still a clinical need to improve recovery from nerve injuriesand a new nerve conduit drug delivery device that addresses this clinical need is the focus of the present proposalOur group has developed a patented drug delivering conduit for use in peripheral nerve surgery that can release growth factors and or small molecules in a controlled manner to the regenerating nerve and can be used in a variety of peripheral nerve injury or repair applicationsBy taking advantage of the simple physical process of diffusion we have designed a hole based drug delivery system that demonstrates controlled releaseIn this proposal we plan to use our unique nerve conduit device to locally deliver a neurotrophic small moleculeFKThe overall objective is to demonstrate that our patented nerve conduitthat locally releases FKcan enhance functional recovery when used ito bridge a nerve gap and iiin conjunction with autologous nerve graft repair of a peripheral nerve injury in a rat sciatic nerve modelIn Aima we will utilize rapid prototyping to manufacture a device that can release FKfordays at a concentrationng mLthat has been shown to be neurotrophicWe will evaluate the FKrelease kinetics over the release period using a commercially available ELISAWe will then evaluateAimbthe efficacy of our nerve guide drug delivery device to improve functional outcomesas measured by sciatic functional index and muscle atrophyin two different rat sciatic nerve surgical repair strategiesto bridge a nerve gap andin conjunction with autologous nerve graft repairWe will evaluate the primary outcome variablessciatic functional index and muscle atrophyand secondary measures including nerve histomorphometryneuromuscular junction connectivityand electrophysiology atdays post surgeryWe expect to see greater improvements in functional recovery when the sciatic nerve injury is repaired with the combination of standard surgical repair AND local FKdelivery compared to standard repair aloneWe have set to two primarygono gomilestones to provide sufficient evidence for continuation of the commercialization plan and warrant Phase II fundingOur FKreleasing device will result in statistically greater improvements in functional recoverygait and muscle massthan an FDA approved device and equivalent to an autograft in bridging acm nerve gap andOur FKdevice combined with an autograft will have statistically better functional outcomes than treatment of acm gap injury with autograft aloneThis approach of locally releasing FKfrom our novel drug delivering conduit could potentially transform current nerve repair strategies and dramatically improve the functional outcomes following peripheral nerve repair Project Narrative Peripheral nerve injuries such as those that occur with traumafracturesor nerve plexus injuries are particularly devastating and often have few treatment optionsmost of which result in long term disabilitiesOur approach of locally releasing neurotrophic drugs from a novel drug delivering conduit could potentially transform current nerve repair strategies and dramatically improve the functional outcomes following peripheral nerve repair