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“块状共混”策略制备的可注射温敏水凝胶作为内镜黏膜下剥离术的生物材料

Injectable Thermogel Generated by the "Block Blend" Strategy as a Biomaterial for Endoscopic Submucosal Dissection.

机构信息

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200438, China.

Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Shanghai 200032, China.

出版信息

ACS Appl Mater Interfaces. 2021 May 5;13(17):19778-19792. doi: 10.1021/acsami.1c03849. Epub 2021 Apr 21.

Abstract

Endoscopic submucosal dissection is an established method for the removal of early cancers and large lesions from the gastrointestinal tract but is faced with the risk of perforation. To decrease this risk, a submucosal fluid cushion (SFC) is needed clinically by submucosal injection of saline and so on to lift and separate the lesion from the muscular layer. Some materials have been tried as the SFC so far with disadvantages. Here, we proposed a thermogel generated by the "block blend" strategy as an SFC. This system was composed of two amphiphilic block copolymers in water, so it was called a "block blend". We synthesized two non-thermogellable copolymers poly(d,l-lactide--glycolide)--poly(ethylene glycol)--poly(d,l-lactide--glycolide) and blended them in water to achieve a sol-gel transition upon heating in both pure water and physiological saline. We explored the internal structure of the resultant thermogel with transmission electron microscopy, three-dimensional light scattering, C NMR, fluorescence resonance energy transfer, and rheological measurements, which indicated a percolated micelle network. The biosafety of the synthesized copolymer was preliminarily confirmed . The main necessary functions as an SFC, namely, injectability of a sol and the maintained mucosal elevation as a gel after injection, were verified . This study has revealed the internal structure of the block blend thermogel and illustrated its potential application as a biomaterial. This work might be stimulating for investigations and applications of intelligent materials with both injectability and thermogellability of tunable phase-transition temperatures.

摘要

内镜黏膜下剥离术是一种成熟的方法,用于从胃肠道中切除早期癌症和大病变,但存在穿孔的风险。为了降低这种风险,临床上需要通过黏膜下注射生理盐水等方法来形成黏膜下液垫(SFC),以将病变从肌肉层抬起并分离。迄今为止,已经尝试了一些材料作为 SFC,但都存在缺点。在这里,我们提出了一种由“嵌段共混”策略产生的温敏凝胶作为 SFC。该系统由两种两亲性嵌段共聚物在水中组成,因此被称为“嵌段共混物”。我们合成了两种非温敏性共聚物聚(DL-丙交酯-乙交酯)-聚(乙二醇)-聚(DL-丙交酯-乙交酯),并将其在水中混合,在纯水中和生理盐水中加热时均可实现溶胶-凝胶转变。我们通过透射电子显微镜、三维光散射、C NMR、荧光共振能量转移和流变学测量研究了所得温敏凝胶的内部结构,表明存在贯通的胶束网络。合成共聚物的生物安全性得到了初步确认。验证了作为 SFC 的主要必要功能,即溶胶的可注射性以及注入后凝胶保持黏膜升高的能力。本研究揭示了嵌段共混温敏凝胶的内部结构,并说明了其作为生物材料的潜在应用。这项工作可能会激发对具有可注射性和温敏凝胶性以及可调相变温度的智能材料的研究和应用。

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