Nobuhiro Hakuba1, Yasuhiko Tabata, Naohito Hato, Takashi Fujiwara, Kiyofumi Gyo. 1. *Department of Otolaryngology-Head and Neck Surgery, Ehime University School of Medicine, Ehime; and †Department of Biomaterials, Field of Tissue Engineering, Kyoto University School of Medicine, Kyoto, Japan.
Abstract
HYPOTHESIS: In this developmental research study that aimed to develop tympanic membrane regeneration therapy, we devised a method of sustained bFGF formulation release using gelatin hydrogel in a guinea pig eardrum perforation model. BACKGROUND: Basic fibroblast growth factor (bFGF) can promote perforation closure. In addition, several studies of bFGF formulations have used gelatin hydrogel-bFGF coupled electrostatically to a gelatin polymer. BFGF is released gradually as a result of degradation of the gelatin polymer, and studies have shown that the long-term pharmacologic effects of bFGF can be maintained. METHODS: Using a CO(2) laser, total tympanic membrane perforations were created in 24 guinea pig ears and divided into 3 groups: the bFGF-gelatin hydrogel group(n = 8), the saline-gelatin hydrogel group (n = 8), and the control group (n = 8). Either a bFGF formulation or saline was impregnated into gelatin hydrogen and implanted into the perforated tympanic membrane. RESULTS: All ear drums of the control group showed large perforations at even the 30th postoperative day. The perforation persisted in 3 of 8 ears in the saline-gelatin hydrogel group, and the tympanic membranes that had achieved closure were thinned, whereas all ears in the bFGF-gelatin hydrogel group achieved closure of the perforation. In the ears in which a normal tympanic membrane had regenerated, histologic observation with hematoxylin and eosin staining revealed that, although mucosal and epithelial layer regeneration had occurred in the saline-gelatin hydrogel group, the bFGF-gelatin hydrogel group showed regeneration of the fibrous layer in addition to the other 2 layers. CONCLUSION: These data suggest that hydrogel impregnated with bFGF induces regeneration of the tympanic membrane and can conservatively treat tympanic membrane perforation.
HYPOTHESIS: In this developmental research study that aimed to develop tympanic membrane regeneration therapy, we devised a method of sustained bFGF formulation release using gelatin hydrogel in a guinea pig eardrum perforation model. BACKGROUND:Basic fibroblast growth factor (bFGF) can promote perforation closure. In addition, several studies of bFGF formulations have used gelatin hydrogel-bFGF coupled electrostatically to a gelatin polymer. BFGF is released gradually as a result of degradation of the gelatin polymer, and studies have shown that the long-term pharmacologic effects of bFGF can be maintained. METHODS: Using a CO(2) laser, total tympanic membrane perforations were created in 24 guinea pig ears and divided into 3 groups: the bFGF-gelatin hydrogel group(n = 8), the saline-gelatin hydrogel group (n = 8), and the control group (n = 8). Either a bFGF formulation or saline was impregnated into gelatin hydrogen and implanted into the perforated tympanic membrane. RESULTS: All ear drums of the control group showed large perforations at even the 30th postoperative day. The perforation persisted in 3 of 8 ears in the saline-gelatin hydrogel group, and the tympanic membranes that had achieved closure were thinned, whereas all ears in the bFGF-gelatin hydrogel group achieved closure of the perforation. In the ears in which a normal tympanic membrane had regenerated, histologic observation with hematoxylin and eosin staining revealed that, although mucosal and epithelial layer regeneration had occurred in the saline-gelatin hydrogel group, the bFGF-gelatin hydrogel group showed regeneration of the fibrous layer in addition to the other 2 layers. CONCLUSION: These data suggest that hydrogel impregnated with bFGF induces regeneration of the tympanic membrane and can conservatively treat tympanic membrane perforation.