Adhesive Submucosal Injection Material Based on the Nonanal Group-Modified Poly(vinyl alcohol)/α-Cyclodextrin Inclusion Complex for Endoscopic Submucosal Dissection

Complete resection of early-stage cancer and subsequent wound care of the resection site are both important factors for successful endoscopic submucosal dissection (ESD). Although many submucosal injection materials (SIMs) have been developed to lift up lesions and completely remove cancers, a lack of materials with multiple functions, such as stable submucosal cushion formation, emergency perforation closure, and blood coagulation and wound sealing abilities, still exists. In this study, an adhesive submucosal injection material based on nonanal group-modified poly(vinyl alcohol) (C9-PVA) and alpha-cyclodextrin (alpha-CD) was developed to solve clinical problems associated with ESD. Focusing on the inclusion ability of alpha-CD for alkyl groups, a water-soluble alpha-CD/C9-PVA inclusion complex (IC) was prepared using water-insoluble C9-PVA in aqueous solutions. The IC of 2.5 mol % nonanal group-modified PVA (2.5C9-PVA), with 53 mM alpha-CD, showed good gel-sol reversibility and high injectability. Additionally, the alpha-CD/2.5C9-PVA IC performed well at submucosal cushion formation, with the increased height reaching 5.90 +/- 0.38 mm. The complex also adhered well to the submucosa, successfully sealing wounds for over 7 days even in an aqueous environment. Furthermore, following incubation in physiological saline (1.80 +/- 0.37 kPa), the burst strength of the alpha-CD/2.5C9-PVA IC was 1.5-fold higher compared with that of the commercial fibrin sealant, illustrating the possibility of emergency perforation closure. Finally, the complex promoted blood coagulation when mixed with fresh porcine whole blood. These results indicate that the multifunctional alpha-CD/2.5C9-PVA IC could be an ideal material for ESD.