Injectable Hyaluronic Acid-Based Hydrogels for Rapid Endoscopic Submucosal Dissection

Endoscopic submucosal dissection (ESD) is a widely used procedure for the treatment of early and precancerous gastrointestinal lesions and has become the standard treatment. In this procedure, the commonly used materials have a short retention time and a limited lifting capacity, which will prolong the duration of the ESD procedure. Furthermore, these liquids tend to diffuse after ESD surgery, failing to adequately protect the wound. Therefore, we designed and developed injectable hydrogels based on hyaluronic acid. A series of oxidized hyaluronic acid (OHA) and hydrazide hyaluronic acid (AHA) were synthesized, and 16 kinds of injectable hydrogels were fabricated to investigate the effects of molecular structures on the properties of the hydrogels. Among these, the O1A3 hydrogel exhibited a suitable injection performance, gelation time, and mechanical properties, along with good blood and cell compatibility <i>in vitro</i>. Subsequently, in a porcine model of the ESD procedure, the results demonstrated that the O1A3 hydrogel exhibited a good retention time and lifting performance while also significantly reducing the operation time from 1-2 h to ∼10 min. Furthermore, the adhesive property of the O1A3 hydrogel on small bleeding spots and wounds could be observed, which was beneficial in protecting the wound from the complex environment of the gastrointestinal tract. The present work of injectable hyaluronic acid-based hydrogels could be promising to improve the efficiency of ESD surgery.