Developing A Long-term Survival Swine Hemi-facial Vascularized Composite Allotransplantation Model To Study Facial Nerve Regeneration

 

PURPOSE: We present a survival large animal model for preclinical facial transplant research to evaluate facial nerve regeneration. 

 

METHODS: 19 survival surgeries (16 auto-transplant, 3 allotransplant) were performed to develop and validate a hemi-facial composite flap to evaluate nerve regeneration (Fig 1). Assessment of nerve regeneration using serial compound muscle action potentials (CMAP), electroneurograms (ENG) and histology in a 3-4 month survival model was established. Immunosuppression in allotransplanted pigs started on POD-3 and maintained with weight-based Cyclosporin (CSA) (target levels of 200-300), mycophenolic acid and prednisone. Postoperative course and complications were documented. 

 

RESULTS: The buccal facial nerve branch was selected the most optimal to assess nerve regeneration using nerve conduction studies. In our allotransplant and auto-transplant models minor wound breakdown and sialoceles were managed conservatively or superficial debridement in the first 4-6 weeks. There were no flap losses. No systemic infections were experienced in the allotransplanted pigs(n=3); one pig developed an abscess requiring debridements, extended antibiotics usage, but complete resolution at 8 weeks. At 3 months nerve regeneration reached 75% distance to target muscle with comparable ENG to normal side in auto-transplanted Sinclair mini-pig group (n=5), but a slower rate of regeneration in the allotransplanted group (n=3). 

 

CONCLUSION: This study demonstrates proof of concept for an allotransplant large experimental animal model for research to inform post-surgical care to improve facial nerve regeneration and functional outcomes.