Prospective transfrontal sheep model of skull-base reconstruction using vascularized mucosa

No high-fidelity animal model exists to examine prospective wound healing following vascularized reconstruction of the skull base. Such a model would require the ability to study the prospective behavior of vascularized mucosal repairs of large dural and arachnoid defects within the intranasal environment. The objective of this study was to therefore develop and validate a novel, in vivo, transfrontal sheep model of cranial base repair using vascularized sinonasal mucosa.

Twelve transfrontal craniotomy and 1.5-cm durotomy reconstructions were performed in 60-kg to 70-kg Dorset/Ovis Aries sheep using vascularized mucosa with or without an adjunctive Biodesign™ underlay graft (n = 6 per group). Histologic outcomes were graded (scale, 0 to 4) by a blinded veterinary histopathologist after 7, 14, and 28 days for a range of wound healing parameters.

All sheep tolerated the surgery, which required 148 ± 33 minutes. By day 7, the mucosa was fully adherent with complete partitioning of the sinus and intracranial compartments. Fibroblast infiltration and flap neovascularization scores significantly increased between day 7 (0.3 ± 0.5 and 0.0 ± 0.0) and day 28 (4.0 ± 0.0, p = 0.01 and 2.0 ± 0.8, p = 0.01; respectively), while hemorrhage scores significantly decreased from 2.5 ± 0.6 to 0.0 ± 0.0 (p = 0.01). The inflammatory scores were not significantly different between the heterologous graft and control sides.

The described sheep model accurately reflects prospective intranasal wound healing following vascularized mucosal reconstruction of dural defects. This model can be used in future studies to examine novel reconstructive materials, tissue glues, and transmucosal drug delivery to the central nervous system.