Injectable pullulan hydrogel for the prevention of postoperative tissue adhesion

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• 作者：Sumi Bang^a ; Eungjae Lee^a ; Young-Gwang Ko^a ; Won Il Kim^b ; Oh Hyeong Kwon^a ; ^{ohkwon@kumoh.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Hydrogel ; Pullulan ; Enzymatic reaction ; Anti-adhesion barrier
• 刊名：International Journal of Biological Macromolecules
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：87
• 期：Complete
• 页码：155-162
• 全文大小：1512 K

文摘

Methods for reducing and preventing postoperative abdominal adhesions have been researched for decades; however, despite these efforts, the formation of postoperative peritoneal adhesions is continuously reported. Adhesions cause serious complications such as postoperative pain, intestinal obstruction, and infertility. Tissue adhesion barriers have been developed as films, membranes, knits, sprays, and hydrogels. Hydrogels have several advantages when used as adhesion barriers, including flexibility, low tissue adhesiveness, biodegradability, and non-toxic degraded products. Furthermore, compared with preformed hydrogels, injectable hydrogels can fill and cover spaces of any shape and do not require a surgical procedure for implantation. In this study, pullulan was modified through reaction with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) to introduce carboxyl and phenyl groups as crosslinking sites. The grafting of tyramine on pullulan allows crosslinking branches on pullulan backbone. We successfully fabricated pullulan hydrogel with an enzymatic reaction using horseradish peroxidase (HRP) and hydrogen peroxide (H₂O₂). The chemical structure of modified pullulan was analyzed with ATR-FTIR and ¹H NMR spectroscopies. Rheological properties were tested by measuring storage modulus with varying H₂O₂, HRP, polymer solution concentrations and tyramine substitution rates. Cell viability and animal tests were performed. The modified pullulan hydrogel is an invaluable advance in anti-adhesion agents.