Adhesive Hemostatic Hydrogel with Ultrafast Gelation Arrests Acute Upper Gastrointestinal Hemorrhage in Pigs

Abstract

Upper gastrointestinal (GI) hemorrhage is a common clinical emergency worldwide. Endoscopic hemostasis is the current first line treatment. Nevertheless, for patients with severe active bleeding and challenging anatomy, endoscopic management can be still difficult and usually requires a higher level of surgical expertise. A simple and effective method of endoscopic hemostasis is therefore in acute clinical demand. Herein a hemostatic hybrid hydrogel comprised of hyaluronic acid and polyethylene glycol stabilized by thiourea-catechol coupling and disulfide bonds is reported. The hybrid hydrogels exhibit enhanced mechanical properties, short gelation time, and good blood clotting ability compared with fibrin gels. The in vivo hemostatic efficacy is confirmed in a rat model of arterial bleeding, in which the rapid gelation of hybrid hydrogels after topical application effectively arrests blood loss with no rebleeding occurring during resuscitation when blood pressure approximately recovers to normal. A large animal study further demonstrates the efficacy of hybrid hydrogels to achieve endoscopic hemostasis against upper GI hemorrhage in pigs. Follow-up observations show that the hybrid hydrogels can remain adherent at the bleeding wound for 48 h, indicating the sustained hemostatic function in vivo. Collectively, this work demonstrates a promising hemostatic hydrogel for endoscopic hemostasis in upper GI hemorrhage.

Engineered Hemostatic Biomaterials for Sealing Wounds

“…Injectable hydrogels are based on in situ cross-linking of prepolymer solutions upon application to the wound site, which enable filling complex-shaped voids, full coverage of wounds, and integration with minimally invasive surgeries . Hydrogel beads also have shown the capacity for injectability and demonstrated the potential for hemostatic applications. ,, Fast gelation of injectable hydrogels is of great importance to seal the bleeding area physically. − Wound dressings can be designed in the form of wet hydrogels, dry patches, and particles. , Hemostasis in wet hydrogels is mostly based on chemical interactions with blood plasma, whereas dry patches, in the form of membranes, microneedle arrays, , electrospun mats, textiles, sponges, and cryogels, as well as aerogels, can promote hemostasis through both plasma absorption and interactions with blood plasma components similar to hemostatic particles. Solutions of hemostatic particles can be sprayed for easier application on the wound site .…”

“…Wound dressings have also accelerated subsequent stages of wound healing (i.e., inflammation, proliferation, and remodeling) due to their intrinsic wound healing promoting effects and capacity to load various drugs . Hemostatic materials and smart hemostatic devices are rapidly being developed to address various clinical needs such as cardiac, arterial, and gastrointestinal hemorrhage. , Blood coagulation during implantation of indwelling needles and bleeding after their withdrawal are the main problems with the current needles. A smart indwelling with switchable hemostasis was developed wherein the hemostatic properties could be controlled using a magnetic field .…”

Hemostatic biomaterials to halt non-compressible hemorrhage

“…7f). 123 Such adhesive hydrogels achieve endoscopic hemostasis against upper gastrointestinal (GI) hemorrhage in pigs and remain adherent at the bleeding wound for 48 hours, indicating sustained hemostatic function in vivo .…”

In situ forming injectable γ-poly(glutamic acid)/PEG adhesive hydrogels for hemorrhage control

“…Besides, the obtained adhesive strength of the PGA-PEG hydrogels (13-15 kPa) was comparable to those of the recently developed adhesive hydrogels and sufficient to be used for hemostasis. 50,51…”