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Tacrolimus releasing nerve wraps accelerate peripheral nerve regeneration after axotomy
Joshua M. Barnett, Bo Xiao, Firuz Feturi, Yolandi van der Merwe, Xinzhu Gu, Evan Katzel. Raman Venkataramanan, Mario G. Solari, William Wagner, Daniel Simons, Michael B. Steketee, Kia M. Washington
University of Pittsburgh School of Medicine
2018-02-13
Presenter: Joshua M. Barnett
Affidavit:
This was a collaborative original work by all authors stated. Each author contributed to experimental design, data collection, or analyses and write-up.
Director Name: Kia M. Washington
Author Category: Medical Student
Presentation Category: Basic Science Research
Abstract Category: Hand
Introduction
Peripheral nerve injuries can lead to permanent functional disabilities. Systemic tacrolimus administration can improve recovery and functional outcomes after nerve injury repair. However, high systemic levels of tacrolimus can result in adverse side-effects. Localized administration of tacrolimus could provide the neuroregenerative benefits while avoiding off-target side-effects. This study investigates the utility of a novel tacrolimus-infused nerve wrap in treating peripheral nerve injuries in a rat infraorbital nerve transection and repair model.
Methods
Infraorbital nerve transection surgeries were performed on two groups (n=5) of Lewis rats. Transected nerves were repaired primarily with (treatment group) or without (no treatment group) the addition of a Poly(ester urethane) urea (PEUU) wrap infused with 20mg of tacrolimus. Trigeminal ganglion cell recordings, objective sensory testing, directional sensitivity, maximal response, and receptor compositions were analyzed at four and six weeks postoperatively. Blood and tissue samples were analyzed for tacrolimus concentration using LCMS spectrometry.
Results
Treatment group rats were found to have increased response magnitude at 4 weeks postoperatively in comparison to no treatment group (p<.013). Tacrolimus blood levels at 4 and 6 weeks were close to the limit of quantification (<2ng/ml), whereas concentration within the tissues of interest were much higher.
Conclusion
This study investigates the use of a tacrolimus-impregnated nerve wrap to improve functional recovery following peripheral nerve injury. The tacrolimus wraps appear to accelerate nerve recovery at 4 weeks, with minimal systemic drug exposure. The findings from this study may translate into novel treatment systems and protocols to treat nerve injuries.
