Encapsulation of growth factors in acellular nerve allografts for peripheral nerve regeneration
Bliley, Jacqueline M.
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Background: Nerve injuries can occur due to trauma, tumor removal, and accidental surgical resection. Standard care for a peripheral nerve transection involves excising a portion of a non-essential sensory nerve (i.e., an autograft), such as the sural nerve. This donor nerve is then transplanted into the defect. Although autografts are considered the clinical standard of peripheral nerve repair, they also pose significant disadvantages for patients. Nerve autografts contribute to loss of sensory function and the production of neuromas at the donor site. Surgeons are limited in the number and diameter of nerves that can be harvested. This can complicate trauma situations in which multiple peripheral nerve injuries are sustained. When an autograft is not available, nerve guides are often used to reconstruct defects less than 3 em. To date, there is no commercially available guide that is Food and Drug Administration (FDA)-approved to repair long gap peripheral nerve defects (i.e. gaps > 3 em). Our research has aimed to counteract this deficit in care by investigating nerve conduit therapies that are able to promote repair over long gaps. The combination of synthetic poly(caprolactone) with a native nerve guide structure and a neurotrophic factor delivery system should promote peripheral nerve repair over long gaps. Methods: Poly(caprolactone) nerve guides were fabricated with an internal drug delivery system in the form of double-walled microspheres. Double-walled microspheres were encapsulated with glial cell line-derived neurotrophic factor (GDNF), a prominent growth factor indicated in nerve repair. The poly(caprolactone) was embedded with double-walled microspheres and wrapped around a decellularized nerve allograft to form a novel nerve guide with synthetic and native components. A prototype of this novel guide was developed and scanning electron microscopy was used to further assess nerve guide structure. Results: Scanning electron microscopy revealed smooth and round microspheres with a double-walled morphology. Scanning electron microscopy also revealed the presence of intact endoneurial tubules within the acellular nerve allograft. Conclusion: A novel synthetic-native nerve guide with an internal neurotrophic factordelivery system was created to support repair of large peripheral nerve defects (i.e. defects greater than 3 centimeters).
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