Designing a Novel Drug Delivering Nerve Guide: A Preliminary Study
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Peripheral nerve lesions caused by trauma often require the removal of the injured segment of nerve and subsequent surgical repair. Nerve injuries that produce large gaps require a “bridge” to guide axon growth. Autografts are currently the gold standard for bridging that gap but they have drawbacks including donor site morbidity and limited donor sites. Surgically implanting a nerve guidance conduit is an alternative solution to grafting. The conduits can provide guidance for the regenerating axons and allow for tension free bridging. We present a bioresorbable drug delivery conduit that relies on the mechanics of diffusion to locally deliver neurotrophins to the regeneration site. The drug delivery conduit was fabricated using solvent casting and tested for release kinetics using dextran and nerve growth factor. A drug diffusion model was also developed to test the reliability and predictability of our device, and finally the bioactivity of the released media was evaluated by measuring neurite extension in dorsal root ganglia (DRG). The results of the in vitro drug release tests showed that diffusion of drug through our conduits could be tuned by varying the hole size and reservoir size. Linear scaling can be achieved by modifying the initial concentration of drug loaded in the reservoir. The drug delivery nerve conduit was able to release bioactive NGF for 8 days and enhance DRG neurite extension. The drug delivery nerve conduit can release bioactive drugs predictably and has the potential to improve nerve regeneration following a peripheral nerve injury.
KeywordsPoly lactic-co-glycolic acid (PLGA) Nerve conduit Drug delivery Diffusion model
The authors thank their colleagues at the State of Utah Center of Excellence for Biomedical Microfluidics and the Department of Surgery Research Laboratory for their assistance in this work.
This work is funded by the DOD Award Number W81XWH1310363.
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