Effect of in Vivo Oxidized Cellulose on in Vitro Growth of Human Respiratory Mucosa and Sub-mucosa During Endoscopic Skull Base Approaches

Introduction: Despite major progress in closure techniques for endoscopic endonasal skull base approaches, cerebrospinal fluid (CSF) leakage remains a common complication after these procedures. Because it simultaneously aids hemostasis and adheres the mucosal flap to the skull base, regenerated oxidized cellulose (ROC) (Surgicel™¸ Ethicon, USA) sheets have gained popularity as an adjunct to a vascularized nasoseptal flap for closure of large dural defects. However, evidence supporting the positive impact of ROC on the healing process is uncertain. Methods: In 6 patients, a 1 cm2 piece of ROC gauze was placed on the surface of the middle turbinate and sphenoid mucosa before they were resected as part of a standard endoscopic endonasal approach (EEA). After removal, mucosa treated with ROC was separated from untreated mucosa (control), and the two groups were compared. A histological examination of structural changes, cell viability, and growth capacity was performed. All experiments compared control samples to samples exposed to ROC. Tissue structure was analyzed by common histological techniques. A cell culture derived from the nasal mucosa and sub-mucosa was performed. Cells were characterized by common staining techniques and immunohistochemistry for cytokeratin and vimentin as markers for epithelial and mesenchymal cells, respectively. To evaluate for cell viability, a mixed solution containing acridine orange and ethidium bromide was added to the surface of the sphenoid mucosa and the middle turbinate immediately after they were harvested. Results: Compared with the unexposed controls, exposed tissues exhibited extensive necrosis, including destruction of the endothelial lining of blood vessels and the respiratory epithelium. Treatment with ROC induced cellular death in both samples and in every specimen. In the viability assays, the number of viable (green) nuclei were substantially diminished and replaced by non-viable (red) ones. Finally, control specimens could be grown in cell cultures. Two different kinds of cells could be seen. One cell type had long fusiform cytoplasm and grew in a typical fusiform pattern and the other cell type exhibited a polygonal shape with a chaotic intercellular arrangement corresponding to mesenchymal and epithelial origins, respectively. Mixed positivity for cytokeratin and vimentin was observed, confirming the presence of both epithelial and mesenchymal cells in the culture. In sharp contrast, specimens that were tre