Endoscopy Deliverable and Mushroom-Cap-Inspired Hyperboloid-Shaped Drug-Laden Bioadhesive Hydrogel for Stomach Perforation Repair

Abstract

Gastrointestinal tract perforation is a full-thickness injury that causes bleeding and fatal infection of the peritoneum. This condition worsens in an acidic gastric environment which interferes with the normal coagulation cascade. Current endoscopic clips to repair gastric perforations are ineffective, and metal or plastic occluders need secondary surgery to remove them. Herein, we report a self-expandable, endoscopy deliverable, adhesive hydrogel to block gastric perforation. We found the nanosilica coating significantly enhanced the adhesive strength even under a simulated strong acidic stomach environment. The developed device was disulfide cross-linked for the reducible degraded gel. By loading with vonoprazan fumarate (VF) and acidic fibroblast growth factor (AFGF), the hyperboloid-shaped device can have a sustained drug release to regulate intragastric pH and promote wound healing. The gel device can be compressed and then expanded like a mushroom when applied in an acute gastric perforation model in both rabbits and minipigs. By utilizing a stomach capsule robot for remotely monitoring the pH and by immunohistochemical analysis, we demonstrated that the compressible hyperboloid-shaped gel could stably block the perforation and promoted wound healing during the 28 days of observation. The real-time pH meter demonstrated that the gel could control intragastric pH above 4 for nearly 60 h to prevent bleeding.

Aligned nanofibrous collagen membranes from fish swim bladder as a tough and acid-resistant suture for pH-regulated stomach perforation and tendon rupture

“…Gastric perforation may cause severe peritonitis even death after stomach contents flow into the abdominal cavity [55,56]. Although novel preventive and therapeutic measures are being explored [57,58], the usual treatment is still stitching fistula, requiring better suture acid resistance to low pH in the stomach. Catgut, one of the commonly used sutures in the surgery, is verified rapid strength loss in simulated gastric acid (Fig.…”

Tissue adhesives for wound closure

“…A variety of technics, such as sutures and staples, are widely employed to sustain anastomotic conservation. However, anastomotic leakage can still happen in as high as 23% of cases, and low colorectal and coloanal anastomoses can lead to increased mortality 98 . In recent years, tissue adhesives have been developed to enhance the lines of sutures and staples for the prevention of leakage 27,99–101 .…”

“…However, anastomotic leakage can still happen in as high as 23% of cases, and low colorectal and coloanal anastomoses can lead to increased mortality. 98 In recent years, tissue adhesives have been developed to enhance the lines of sutures and staples for the prevention of leakage. 27,[99][100][101] Various materials are employed as GI tissue adhesives, such as fibrin, albumin-based, PEG-based, and gelatin-based adhesives.…”

Recent advances in hydrogels for preventing tumor recurrence

“…128 These hydrogels often showed strong mechanical properties and stability so that the matrix can be fixed to the surgical site to prevent the leaking of loaded drugs. 129 However, there is a tremendous need to remove these hydrogels by degradation approaches due to their non-degradability in the organism. 130 Besides, dispersed nanoparticles can be added to combine with hydrogels to endow hydrogels with enhanced mechanical capabilities.…”