Latent stem cell-stimulating therapy for regeneration of chronic tympanic membrane perforations using IGFBP2-releasing chitosan patch scaffolds

Abstract

Chronic tympanic membrane perforation is a tubotympanic disease caused by traumatic or inflammatory factors. To date, numerous therapeutic methods have been used to heal tympanic membrane perforations. However, stem cell-based therapies have been used only rarely for the regeneration of chronic tympanic membrane perforations, because tympanic membrane is always exposed to the external environment. Therefore, the use of latent stem cells to treat the tympanic membrane may be possible for the regeneration of chronic tympanic membrane perforations. In the present study, insulin-like growth factor-binding protein 2 (IGFBP2), a cytokine known for stimulating latent epidermal stem cells, was incorporated into chitosan patch scaffolds (CPSs). The IGFBP2-incorporated CPSs (IGFBP-CPSs) were applied to chronic tympanic membrane perforations as a novel therapeutic strategy and stem cell stimulation technique. The IGFBP-CPSs were successfully fabricated and their morphological and mechanical properties evaluated. We conducted an in vitro study to evaluate the release of IGFBP2, as well as analyses of cell viability and wound healing. In rats with chronic tympanic membrane perforations, we found that the IGFBP-CPSs group had a higher success rate (43.8%) than the spontaneous healing group (20.8%). Histological analysis showed that IGFBP-CPSs successfully regenerated tympanic membrane tissues. This stem cell-based method may therefore be a novel and useful therapy for the regeneration of chronic tympanic membrane perforations.