Oxidized fucoidan-based nanocomposite hydrogel for cryptotanshinone delivery and prevention of postoperative abdominal adhesions.

Postoperative abdominal adhesions (PAA) are common diseases following abdominal surgery and can cause various serious complications. The excessive inflammation and oxidative stress are the main causes of PAA formation. Herein, we developed a nanomicellar hydrogel, OFu/HF@CTS, composed of oxidized fucoidan (OFu) and cryptotanshinone (CTS)-loaded hydrazine-functionalized pluronic F127 nanomicelles (HF127@CTS) for the effective prevention of PAA. The hydrogels exhibited satisfactory viscoelasticity, rapid self-healing ability, and good tissue adhesion properties, and were able to slowly release CTS for one week, with a cumulative release rate of 80 % on the 7th day. Additionally, the hydrogels could effectively reduce fibroblast cells and protein adhesions due to the high negative charge of OFu and have good biocompatibility towards RAW 264.7 and L929 cells. Moreover, CTS released from OFu/HF@CTS could efficiently reduce oxidative stress in macrophages and promote M1 macrophages polarized to M2 phenotype to relieve inflammation. In vivo results showed that OFu/HF@CTS hydrogel had good biodegradability and biosafety, and could effectively reduce PAA formation in a rat cecum-abdominal wall abrasion model through the mechanism of alleviating oxidative stress and inflammation, regulating fibrinolysis, and inhibiting fibrosis. This work highlights the therapeutic potential of drug-loaded nanomicellar hydrogels as a preventive strategy for PAA in clinical applications.