Biodegradable And Thermosensitive Monomethoxy Poly(ethylene Glycol)–poly(lactic Acid) Hydrogel As A Barrier For Prevention Of Post-operative Abdominal Adhesion

Objective: Post-operative intestinal adhesion generally occurs in the majority of patients who have undergone abdominal or pelvic surgery. It is a common and serious complication of clinic surgery, and occurs in approximate 80% of abdominal surgical cases. A serious adhesion can lead to discomfort or pain and pathophysiological complications such as infertility, chronic abdominal pain or bowel obstruction, which seriously endangered the health of patients. Therefore, it has important clinical significance for the prevention of postoperative abdominal adhesion. In this study, a novel nano-hydrogel system based on a monomethoxy poly(ethylene glycol)–poly(lactic acid)(MPEG–PLA) di-block copolymer was studied for its ability to prevent abdominal adhesion in rats.Methods:(1) The physicochemical properties and characterization of MPEG-PLA copolymer was carried out by multiple techniques, including Gel permeation chromatography(GPC) and electron scanning microscopy(SEM).(2) The ability of the hydrogel to inhibit adhesion of post-operative tissues in vivo was evaluated by utilizing a rat model of abdominal sidewall-cecum abrasion.(3) The anti-adhesion process ofMPEG-PLA hydrogel was analysed and evaluated using immunohistochemistry and other methods.Results:(1) The MPEG-PLA hydrogels with molecular weight of 9000 and 10000 Da had significant thermal response and its internal structure was a three-dimensional porous structure.(2) The MPEG-PLA hydrogels with a molecular weight of 9000 Da showed a similar effect with commercial gel on preventing postoperative adhesion of abdominal cavity. Ten days after the operation, all the rats in control group appeared adhesion and with separation by excision only. The rats treated with commercial anti-adhesion material in the positive control group and with MPEG-PLA hydrogel, whose abdominal walls and cecums were healed completely, and the wound has no obvious adhesion on the interface. Compared with the negative control group, the postoperative adhesion scores in positive control group and treatment group of MPEG-PLA hydrogel were significantly better than the control group(P < 0.05). However, between the positive control group and MPEG-PLA hydrogel treatment group, there were not statistical significance on postoperative adhesion scoredifference(P > 0.05). After 10 days of operation, the HE staining of adhesion sites showed that the abdominal wall muscle intergrated with the muscle layer of cecal in negative control group, while a new organization layer composed of mesothelial cells was formed in the positive control group and MPEG-PLA group.Conclusions:(1) MPEG-PLA polymer and hydrogel system wassuccessfully synthesized. The physicochemical analysis showed that MPEG-PLA hydrogel had good temperature response and its internal structure was a three-dimensional porous structure;(2) These results in vivo experiments confirmed that MPEG-PLA hydrogel has good prevention of peritoneal adhesions in rats, with similar effect a commercial gel;(3) the study confirmed that MPEG-PLA hydrogel acted as a barrier between the injured tissue interface, whicn aimed to prevent the adhesion effect through the regeneration of mesothelial cell layer. This study showed that MPEG-PLA hydrogel was a kind of effective polymeric biomedical materials, non-toxic, easy degradation, and can be used for the prevention of abdominal adhesion.