Sung-Hee Park

Mastoidectomy is a surgical procedure for the treatment of chronic otitis media. This study investigated the ability of rat stromal vascular fraction cells (rSVF) in combination with polycaprolactone (PCL) scaffolds and osteogenic differentiation-enhancing blood products to promote the regeneration of mastoid bone defect. Twenty male Sprague Dawley rats were randomly divided according to obliteration materials: (1) control, (2) PCL scaffold only, (3) rSVFs + PCL, (4) rSVFs + PCL + platelet-rich plasma, and (5) rSVFs + PCL + whole plasma (WP). At 7 months after transplantation, the rSVFs + PCL + WP group showed remarkable new bone formation in the mastoid. These results indicate that SVFs, PCL scaffolds, and blood products accelerate bone regeneration for mastoid reconstruction. Autologous SVF cells with PCL scaffolds and autologous blood products are promising composites for mastoid reconstruction which can be easily harvested after mastoidectomy. With this approach, the reconstruction of mastoid bone defects can be performed right after mastoidectomy as a one-step procedure which can offer efficiency in the clinical field.

Cisplatin-induced early-onset ototoxicity is linked to hearing loss. The mechanism by which cisplatin causes ototoxicity remains unclear. The purpose of this study was to identify the involvement of receptor-interacting protein kinase (RIP)3-dependent necroptosis in cisplatin-induced ototoxicity in vitro and in vivo. Sprague–Dawley rats (SD, 8 week) were treated via intraperitoneal (i.p.) injection with cisplatin (16 mg/kg for 1 day), and their hearing thresholds were measured by the auditory brainstem response (ABR) method. Hematoxylin and eosin (H & E) staining, immunohistochemistry, and western blots were performed to determine the effect of cisplatin-induced ototoxicity on cochlear morphology. Inhibitor experiments with necrostatin 1 (Nec-1) and Z-VAD were also performed in HEI-OC1 cell line. H&E stains revealed that the necroptotic changes were increased in the organ of Corti (OC) and spiral ganglion neurons (SGNs). Moreover, immunohistochemistry and western blot analysis showed that cisplatin treatment increased the protein levels of RIP3 in both OCs and SGNs. The treatment of Nec-1, a selective RIP1 inhibitor, resulted in markedly suppression of cisplatin-induced cell death in HEI-OC1 cells, whereas Z-VAD treatment did not change the cisplatin-induced cell death. Our results suggest that RIP3-dependent necroptosis was substantial in cisplatin-induced ototoxicity; inner cochlear regions, the OCs, and SGNs were especially sensitive to necroptosis.