Injectable Thermosensitive Chitosan Solution with β-Glycerophosphate as an Optimal Submucosal Fluid Cushion for Endoscopic Submucosal Dissection

Abstract

Endoscopic submucosal dissection (ESD) is a surgical procedure to remove early neoplastic lesions in the gastrointestinal tract with the critical issue of perforation. A submucosal fluid cushion, such as normal saline, is used as a cushioning agent to prevent perforation; however, its cushioning maintenance is insufficient for surgery. In this study, we introduce an injectable thermosensitive chitosan solution (CS) with β-glycerophosphate (β-GP) as a submucosal injection agent for ESD. The CS/β-GP system with optimal β-GP concentration showed drastic viscosity change near body temperature while other commercial products did not. Additionally, the injectability of the solution was similar to or greater than other commercial products. The solution with low β-GP concentration showed low cytotoxicity similar to other products. An in vivo preclinical study illustrated maintenance of the high cushioning of the thermosensitive solutions. These results indicate that a CS/β-GP system with optimal β-GP concentration might be used as a submucosal injection agent in ESD, and further studies are needed to validate the effectiveness of the solutions in vivo.

Technical Advances in Endoscopic Resection Techniques for Lower GI Malignancies

“…A systematic review from 2016 [78] did not find significant benefits of alternative agents in terms of en bloc resection, curative resection, or adverse events.Another cheap and well-known add-on is the adjunction of epinephrine 0.001% to the saline solution. In a large Japanese retrospective case-matched study [79] with proper multivariate analysis, the adjunction of epinephrine solution was associated with a reduction in procedure duration and the occurrence of early bleeding but not of delayed bleeding or perforation.Several solutions have been developed by various manufacturers to address this issue [80‒82]. However, over the last few years, concerns and warnings have been raised about the safety of some of these solutions [83] because they can cause undesirable effects such as the occurrence of an inflammatory reaction and post-procedure pain, granulomas at the resection site [84], retractile scarring that prevents a second ESD in case of recurrence, among others.…”

Injectable Modified Sodium Alginate Microspheres for Enhanced Operative Efficiency and Safety in Endoscopic Submucosal Dissection

“…Normal saline solution (NS) has become the most widely used submucosal injection material due to its convenience and easy availability . However, NS tends to rapidly disperse within the submucosal layer, usually requiring multiple injections to maintain adequate elevation, resulting in an increased risk of bleeding and perforation . Alternative submucosal injection materials have been developed to address the limitations of NS, including hyaluronic acid, glycerol fructose, sodium alginate, hetastarch, and other polysaccharide solutions.…”

“…4 However, NS tends to rapidly disperse within the submucosal layer, usually requiring multiple injections to maintain adequate elevation, resulting in an increased risk of bleeding and perforation. 5 Alternative submucosal injection materials have been developed to address the limitations of NS, including hyaluronic acid, 6 glycerol fructose, 7 sodium alginate, 8 hetastarch, 9 and other polysaccharide solutions. Yamamoto demonstrated that a hyaluronic acid solution exhibits superior lifting effects and a longer maintenance duration compared to saline.…”

Versatile Injectable Carboxymethyl Chitosan Hydrogel for Immediate Hemostasis, Robust Tissue Adhesion Barrier, and Antibacterial Applications

“…Although these biomaterials have demonstrated excellent biocompatibility and biodegradability, their lack of inherent antibacterial properties poses a potential risk of wound infection, motivating the exploration of other antibacterial materials. For instance, antimicrobial polymers like chitosan, lactic acid, and polycaprolactone have been proposed for post-ESD ulcer repair. − However, their high viscosity results in increased injection pressure, adding complexity to the surgical procedure. , While numerous materials have been clinically tested for ulcer repair and bacterial growth inhibition, few have effectively combined wound repair enhancement with bacterial growth inhibition. Furthermore, the widespread clinical application of commercial products, such as collagen tablets and fibrin glue, is limited by their high cost.…”