Viscosity and degradation controlled injectable hydrogel for esophageal endoscopic submucosal dissection

Endoscopic submucosal dissection(ESD)is a common procedure to treat early and precancerous gastrointestinal lesions.Via submucosal injection,a liquid cushion is created to lift and separate the lesion and malignant part from the muscular layer where the formed indispensable space is convenient for endoscopic incision.Saline is a most common submucosal injection liquid,but the formed liquid pad lasts only a short time,and thus repeated injections increase the potential risk of adverse events.Hydrogels with high osmotic pressure and high viscosity are used as an alternate;however,with some drawbacks such as tissue damage,excessive injection resistance,and high cost.Here,we reported a nature derived hydrogel of gelatin-oxidized alginate(G-OALG).Based on the rheological analysis and compare to commercial endoscopic mucosal resection(EMR)solution(0.25%hyaluronic acid,HA),a designed G-OALG hydrogel of desired concentration and composition showed higher performances in controllable gelation and injectability,higher viscosity and more stable structures.The G-OALG gel also showed lower propulsion resistance than 0.25%HA in the injection force assessment under standard endoscopic instruments,which eased the surgical operation.In addition,the G-OALG hydrogel showed good in vivo degradability biocompatibility.By comparing the results acquired via ESD to normal saline,the G-OALG shows great histocompatibility and excellent endoscopic injectability,and enables create a longer-lasting submucosal cushion.All the features have been confirmed in the living both pig and rat models.The G-OALG could be a promising submucosal injection agent for esophageal ESD.