In Situ Fabrication of Double-Layered Hydrogels via Spray Processes to Prevent Postoperative Peritoneal Adhesion

Abstract

Postoperative peritoneal adhesions could cause pelvic pain, infertility, and bowel obstruction. In addition, adhesiolysis makes second surgery difficult. For the first time, we fabricated double-layered hydrogels in situ on the trauma surface via sequential double spray processes to prevent peritoneal adhesions. The spray conditions were optimized for spray distance and gas flow rate to create homogeneous and seamless double-layered hydrogels. The top layer was composed of alginate (Alg)-carboxymethyl cellulose (CMC) and serves as the barrier between the wounded tissue and surrounding tissues. The bottom layer was composed of Alg-gelatin (Gela) and comes in direct contact with the wounded tissue to promote wound healing. In vitro experiments showed that the Alg-Gela hydrogel layer promoted wound healing by accelerating horizontal cell migration. In addition, the Alg-CMC layer prevented the vertical penetration of fibroblast cells. The prevention efficacy of the sprayable double-layered hydrogels was evaluated using a partial hepatectomy-induced adhesion model in rats. The double-layered hydrogels decreased the adhesion grade and extent of liver cut surface, whereas the two single-layered hydrogels, Alg-CMC and Alg-Gela, did not show any adhesion prevention efficacy.