Viscosity and degradation controlled injectable hydrogel for esophageal endoscopic submucosal dissection

Abstract

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.

Biomimetic injectable hydrogel microspheres with enhanced lubrication and controllable drug release for the treatment of osteoarthritis

“…In recent years, injectable hydrogels have been developed with excellent biocompatibility and controlled drug delivery behaviors in tissue engineering [ [7] , [8] , [9] ]. For example, Xin et al .…”

Easily-injectable shear-thinning hydrogel provides long-lasting submucosal barrier for gastrointestinal endoscopic surgery

“…Early gastrointestinal tumor is defined as the lesion that only infiltrates within the submucosa and can be resected by endoscopic surgery [ 3 , 4 ]. Benefiting from the screening strategy toward gastrointestinal lesion, more and more early-stage tumors can be found and treated with endoscopic resection [ [5] , [6] , [7] , [8] , [9] , [10] ]. Endoscopic resection has been indicated to be a popular and effective method for the treatment of early-stage gastrointestinal tumors.…”

“…Due to the foldable and thin features of gastrointestinal tract, the resection of lesion during endoscopic surgery still faces huge challenges such as positive margin, perforation, and bleeding [ [11] , [12] , [13] ]. The application of submucosal injection material (SIM) to form submucosal barrier is a crucial method to satisfy the demand of endoscopic resection [ 5 , 6 ]. SIM is able to elevate lesion by producing a thick liquid cushion, which creates adequate operation spaces between the mucosa and muscularis propria, and shields the electrical and thermal damage generated during the endoscopic resection procedure [ 14 , 15 ].…”

“…Similarly, some hydrogels are found to provide moderate submucosal cushion height because of their high-water content and stiffness, but the inconvenient operation still restricts their applications [ 31 ]. For example, the hydrogels formed by two or more components are inconvenient to be simultaneously injected [ 5 , 32 , 33 ], and photocurable hydrogels require ultraviolet light sources, making the operation difficult under the endoscope [ [34] , [35] , [36] , [37] ]. What's worse, the temperature-sensitive hydrogels have the risk of clogging [ [38] , [39] , [40] , [41] , [42] ].…”

Injectable Thermogel Generated by the “Block Blend” Strategy as a Biomaterial for Endoscopic Submucosal Dissection

“…Therefore, a more durable SFC has been a research focus . Some materials have been proposed as SFCs, but they usually have significant deficiencies. − For example, the SFC of hyaluronic acid (HA) is a relatively long-lasting fluid cushion, and it can achieve en bloc resection and low perforation complication rates. , Nevertheless, HA is expensive and may induce tumor growth factors to promote the proliferation of tumor cells at the wound site . Another example is sodium alginate.…”