Injectable thermosensitive hydrogel containing hyaluronic acid and chitosan as a barrier for prevention of postoperative peritoneal adhesion

Abstract

Peritoneal adhesion is one of the common complications after abdominal surgery. Injectable thermosensitive hydrogel could serve as an ideal barrier to prevent this postoperative tissue adhesion. In this study, poly(N-isopropylacrylamide) (PNIPAm) was grafted to chitosan (CS) and the polymer was further conjugated with hyaluronic acid (HA) to form thermosensitive HA-CS-PNIPAm hydrogel. Aqueous solutions of PNIPAm and HA-CS-PNIPAm at 10%(w/v) are both free-flowing and injectable at room temperature and exhibit sol-gel phase transition around 31°C; however, HA-CS-PNIPAm shows less volume shrinkage after gelation and higher complex modulus than PNIPAm. Cell culture studies indicate both injectable hydrogel show barrier effects to reduce fibroblasts penetration while induce little cytotoxicity in vitro. From a sidewall defect-bowel abrasion model in rats, significant reduction of postoperative peritoneal adhesion was found for peritoneal defects treated with HA-CS-PNIPAm compared with those treated with PNIPAm and untreated controls from gross and histological evaluation. Furthermore, HA-CS-PNIPAm did not interfere with normal peritoneal tissue healing and did not elicit acute toxicity from blood analysis and tissue biopsy examination. By taking advantage of the easy handling and placement properties of HA-CS-PNIPAm during application, this copolymer hydrogel would be a potentially ideal injectable anti-adhesion barrier after abdominal surgeries.