Yu Lin, Xu Wei, Shen Wenjia, Cao Luping, Liu Yan, Li Zhaoshen, Ding Jiandong
State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, People's Republic of China.
Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
Acta Biomater. 2014 Mar;10(3):1251-8. doi: 10.1016/j.actbio.2013.12.007. Epub 2013 Dec 15.
Endoscopic submucosal dissection (ESD) is a clinical therapy for early stage neoplastic lesions in the gastrointestinal tract. It is, however, faced with a crucial problem: the high occurrence of perforation. The formation of a submucosal fluid cushion (SFC) via a fluid injection is the best way to avoid perforation, and thus an appropriate biomaterial is vital for this minimally invasive endoscopic technique. In this study, we introduced an injectable thermogel as a novel submucosal injection substance in ESD. The hydrogel synthesized by us was composed of poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers. The polymer/water system was a low-viscosity fluid at room temperature and thus easily injected, and turned into a non-flowing gel at body temperature after injection. The submucosal injection of the thermogel to create SFCs was performed in both resected porcine stomachs and living minipigs. High mucosal elevation with a clear margin was maintained for a long duration. Accurate en bloc resection was achieved with the assistance of the thermogel. The mean procedure time was strikingly reduced. Meanwhile, no obvious bleeding, perforation and tissue damage were observed. The application of the thermogel not only facilitated the ESD procedure, but also increased the efficacy and safety of ESD. Therefore, the PLGA-PEG-PLGA thermogel provides an excellent submucosal injection system, and has great potential to improve the ESD technique significantly.
内镜黏膜下剥离术(ESD)是一种用于治疗胃肠道早期肿瘤性病变的临床疗法。然而,它面临着一个关键问题:穿孔发生率高。通过液体注射形成黏膜下液垫(SFC)是避免穿孔的最佳方法,因此合适的生物材料对于这种微创内镜技术至关重要。在本研究中,我们引入了一种可注射热凝胶作为ESD中一种新型的黏膜下注射物质。我们合成的水凝胶由聚(乳酸-共-乙醇酸)-聚(乙二醇)-聚(乳酸-共-乙醇酸)(PLGA-PEG-PLGA)三嵌段共聚物组成。聚合物/水体系在室温下是低粘度流体,因此易于注射,注射后在体温下变成非流动凝胶。在切除的猪胃和活体小型猪中均进行了热凝胶的黏膜下注射以形成SFC。高黏膜隆起且边缘清晰,可长时间维持。在热凝胶的辅助下实现了精确的整块切除。平均手术时间显著缩短。同时,未观察到明显出血、穿孔和组织损伤。热凝胶的应用不仅促进了ESD手术,还提高了ESD的疗效和安全性。因此,PLGA-PEG-PLGA热凝胶提供了一种出色的黏膜下注射系统,具有显著改善ESD技术的巨大潜力。