Degradable Temperature-Sensitive Hydrogel Loaded with Heparin Effectively Prevents Post-Operative Tissue Adhesions
Puxin Lang, Tiantian Liu, Shiqi Huang, Zhaojie Zhou, Mengxing Zhang, Yunzhu Lin, He Qin, Yuqin Yao, Zhenmi Liu, Ling Zhang
Abstract
Tissue adhesions could occur following surgeries, and severe tissue adhesions can lead to serious complications. Medical hydrogels could be applied at surgical sites as a physical barrier to prevent tissue adhesion. For practical reasons, spreadable, degradable, and self-healable gels are highly demanded. To meet these requirements, we applied carboxymethyl chitosan (CMCS) to poloxamer-based hydrogels to generate low Poloxamer 338 (P 338 ) content gels displaying low viscosity at refrigerator temperature and improved mechanical strength at body temperature. Heparin, an effective adhesion inhibitor, was also added to construct P 338 /CMCS-heparin composite hydrogel (PCHgel). PCHgel presents as a flowable liquid below 20 °C and could rapidly transform into gel when spread on the surface of damaged tissue due to temperature change. The introduction of CMCS enabled hydrogels to form a stable self-healable barrier at injured positions and slowly release heparin during the wound healing period before being degraded after ∼14 days. Ultimately, PCHgel significantly reduced tissue adhesion in model rats and displayed higher efficiency than P 338 /CMCS gel without heparin. Its adhesion suppression mechanism was verified, and it also displayed good biosafety. Therefore, PCHgel showed good clinical transformation potential with high efficacy, good safety, and ease of use.