Injectable Hybrid Hydrogels, with Cell-Responsive Degradation, for Tumor Resection

Abstract

Biocompatible soft materials have recently found applications in interventional endoscopy to facilitate resection of mucosal tumors. When neoplastic lesions are in organs that can be easily damaged by perforation, such as stomach, intestine, and esophagus, the formation of a submucosal fluid cushion (SFC) is needed to lift the tumor from the underlying muscle during the resection of neoplasias. Such procedure is called endoscopic submucosal dissection (ESD). We describe an injectable, biodegradable, hybrid hydrogel able to form a SFC and to facilitate ESD. The hydrogel, based on polyamidoamines, contains breakable silica nanocapsules covalently bound to its network and able to release biomolecules. To promote degradation, the hydrogel is composed of cleavable disulfide moieties that are reduced by the cells through secretion of glutathione. The same stimulus triggers the breaking of the silica nanocapsules; therefore, the entire hybrid material can be completely degraded and its decomposition depends entirely on the presence of cells. Interestingly, the hydrogel precursor solution showed rapid gelation when injected in vivo and afforded a long-lasting high mucosal elevation, keeping the cushion volume constant during the dissection. This novel material can provide a solution to ESD limitations and promote healing of tissues after surgery.