The feasibility of a novel injectable hydrogel for protecting artificial gastrointestinal ulcers after endoscopic resection: an animal pilot study

Abstract

Recently, covering materials for protecting post-endoscopic ulcers are being developed using hydrogels. Existing hydrogels are not ideal coating materials because it is difficult to control their physical properties. Therefore, we conducted an animal pilot study to investigate the protective effect of a novel ulcer coating material, whose physical properties can be easily controlled and designed. We applied the novel injectable hydrogel to artificial ulcers induced on the gastric mucosa of rats. Rats were assigned to the hydrogel or the control group. To measure the protective effect of hydrogel on ulcers, the perforation rate, ulcer diameter, and ulcer area were evaluated 48 h after gel application. As secondary endpoints, we assessed the residual rate of the hydrogel at the bottom of the ulcer, performed histological analysis, and analyzed adverse events associated with hydrogel. The perforation rate was significantly lower (16% vs. 75%) and the mean diameter of ulcers was significantly smaller (5.4 ± 1.8 mm vs. 7.8 ± 2.8 mm) in the hydrogel group. Histopathological findings revealed the inflammatory cell count was significantly higher in the control group. Our novel hydrogel showed a protective effect on artificial gastric ulcers in a rat model.

Effectiveness and safety of a newly designed self-assembling gel in the treatment of endoscopic submucosal dissection-induced gastric ulcer: A multicenter randomized controlled trial

“…Several studies showed the hemostatic utility of SAPs following endoscopic mucosal resection or ESD for diverse gastrointestinal lesions ( Yoshida et al, 2014 ; Pioche et al, 2016 ; Subramaniam et al, 2019 ). Hydrogels are also being developed and show promising results ( Miura et al, 2021 ). In addition to having a hemostatic function, SAPs were reported to facilitate ulcer healing within the first week and increase the scarring rate at 4 and 8 weeks after ESD ( Uraoka et al, 2016 ).…”

Advances in Hydrogel Adhesives for Gastrointestinal Wound Closure and Repair

“…PEG-based hydrogels containing crosslinked symmetrical tetra-arm macromonomers, of the same size, form homogenous structures with substantial mechanical strength comparable to natural cartilage [ 35 ]. Therefore, many studies report the use of multi-arm PEG as the base material due to its biocompatibility, ease of manufacturing, and high mechanical strength ( Figure 3 A) [ 27 , 36 , 37 , 38 , 39 ]. For example, a tetra-arm PEG-amine (NH 2 ) gels with a NHS functionalized PEG (NHS-PEG-NHS) in 100 s [ 27 ]; a tetra-arm PEG with end-capped thiols (SH) gels with a tetra-arm PEG-maleimide through a thiol-ene reaction in 4 min [ 36 ]; a tetra-arm PEG-NH 2 and a tetra-arm PEG-aldehyde (CHO) gel through Schiff base reactions in 25 s [ 37 ].…”

“…Therefore, many studies report the use of multi-arm PEG as the base material due to its biocompatibility, ease of manufacturing, and high mechanical strength ( Figure 3 A) [ 27 , 36 , 37 , 38 , 39 ]. For example, a tetra-arm PEG-amine (NH 2 ) gels with a NHS functionalized PEG (NHS-PEG-NHS) in 100 s [ 27 ]; a tetra-arm PEG with end-capped thiols (SH) gels with a tetra-arm PEG-maleimide through a thiol-ene reaction in 4 min [ 36 ]; a tetra-arm PEG-NH 2 and a tetra-arm PEG-aldehyde (CHO) gel through Schiff base reactions in 25 s [ 37 ]. All three hydrogel formulations exhibit high storage moduli of over 5 kPa, good adhesive strengths of around 10 kPa, comparable to commercially available adhesives, and short in situ gelation time within 5 min, enabling rapid hemostasis [ 40 ].…”

Brownian simulations for tetra-gel-type phantom networks composed of prepolymers with bidisperse arm length

“…9,10 The network uniformity is a distinguishable feature of tetra gels from the other network polymers, and the studies based on the uniformity have been made both toward fundamental and application directions. 11–15…”

“…9,10 The network uniformity is a distinguishable feature of tetra gels from the other network polymers, and the studies based on the uniformity have been made both toward fundamental and application directions. [11][12][13][14][15] An interesting approach is to utilize tetra gels as reference materials for studying the effects of defects. Sakai et al 16 have conducted such an attempt using tetra gels made of prepolymers with the arm length contrast.…”