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Enhancing Functional Recovery with Local FK506 Hydrogel Treatment in Peripheral Nerve Injury
Fuat Baris Bengur, MD; Chiaki Komatsu, MD; Jocelyn S. Baker, BS; Benjamin K. Schilling, MS; W. Vincent Nerone, BA; Firuz Feturi, PhD; Kacey G. Marra, PhD; Alexander M. Spiess, MD; Mario G. Solari, MD
University of Pittsburgh
2021-02-01
Presenter: Fuat Baris Bengur
Affidavit:
I certify that the material proposed for presentation in this abstract has not been published in any scientific journal or previously presented at a major meeting.
Director Name: Mario G. Solari
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Purpose:
Peripheral nerve injuries result in loss of function and can be associated with long durations of recovery. FK506 (tacrolimus) accelerates the rate of nerve regeneration, however, systemic effects limit its clinical applications. Drug delivery approaches hold promise for local FK506 delivery without systemic side effects. This study aims to assess functional recovery after systemic and local FK506 therapy.
Methods:
In 12 rats, a sciatic nerve transection and repair was performed in four groups: Negative control, systemic FK506, FK506 hydrogel, and empty hydrogel application. Gel was applied locally over the repair site (1.5cm). All groups were followed 7 weeks with weekly FK506 blood concentration and walking track/gait analysis. Electrophysiology was performed to assess gastrocnemius tetanic force.
Results:
Blood FK506 levels in the systemic group were within the therapeutic range throughout the experiment. Blood FK506 levels were not detectable in the local hydrogel-treated group. Both systemic and hydrogel treated groups had a higher functional index than their respective control groups, although statistically not significant. The hydrogel and systemic groups generated similar forces and the hydrogel group generated greater force than its respective control (p<0.001). All contralateral uninjured gastrocnemii showed higher force relative to injured limbs (p<0.0001).
Conclusions:
Local FK506 delivery has the potential to improve functional outcomes after nerve injury, while negating systemic effects. This hydrogel can be easily applied under direct visualization and could be injected under ultrasound guidance. Future studies on molecular mechanisms of nerve regeneration and local dosing can help identify the optimal treatment for different nerve injuries.
