title: Improving Antiadhesion Effect of Thermosensitive Hydrogel with Sustained Release of Tissue-type Plasminogen Activator in a Rat Repeated-Injury Model.
abstract: Intraperitoneal adhesion occurs frequently after pelvic and abdominal surgery, which plays an enormous burden on patients. Various drugs and barrier agents were studied and used to prevent adhesions, but few of them were satisfactory. A thermosensitive hydrogel was developed in our previous work and was effective in preventing adhesions. But in our preliminary experiment, it showed limited activity in a more rigorous rat repeated-injury adhesion model, which was much closer to clinical. In this study, tissue-type plasminogen activator (tPA) loaded thermosensitive hydrogel (tPA-hydrogel) was prepared, which combined barrier functions with sustained release of antiadhesion drug. The obtained tPA-hydrogel was injectable and degraded in vivo gradually in four weeks. Both hematoxylin and eosin and Masson trichrome staining confirmed that the tPA-hydrogel exhibited excellent antiadhesion effects on repeated-injury adhesion. Scanning electron microscopy was used to observe the injured abdominal wall, and cecum remesothelialized after treated with tPA-hydrogel for 14 d. In addition, the PAI-1 and tPA levels were measured by enzyme-linked immunosorbent assay. Results showed the PAI-1 concentrations in peritoneal lavage fluids of tPA-hydrogel treated rats were lower than that of other groups, leading to decreased fibrin formation, while there were no significant differences observed in tPA blood levels at any point in time (P > 0.05). This study demonstrated that the effectiveness of thermosensitive hydrogel in preventing adhesions could be enhanced by delivering antiadhesion drugs, and the tPA-hydrogel might be a promising system for clinical application.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu 610041, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu 610041, P. R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu 610041, P. R. China.
authors.forename: Linjiang
authors.initials: L
authors.lastname: Song
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu 610041, P. R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu 610041, P. R. China.
authors.forename: Suleixin
authors.initials: S
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu 610041, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu 610041, P. R. China.
authors.forename: Qinjie
authors.initials: Q
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu 610041, P. R. China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, China National Cancer Center , Beijing 100021, P. R. China.
authors.forename: Yingtai
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu 610041, P. R. China.
authors.forename: Changyang
authors.initials: C
authors.lastname: Gong
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations; D020100:Hydrogels; D010537:Peritoneum; D051381:Rats; D000267:Tissue Adhesions; D010959:Tissue Plasminogen Activator / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D010959:Tissue Plasminogen Activator
keywords: biodegradable; hydrogel; peritoneal adhesion; repeated-injury; thermosensitive; tissue-type plasminogen activator