设计和验证用于内镜黏膜下剥离术的性能导向型可注射壳聚糖温敏水凝胶。
Design and validation of performance-oriented injectable chitosan thermosensitive hydrogels for endoscopic submucosal dissection.
机构信息
School of Medicine, Southwest Jiaotong University, Chengdu, Sichuan 610064, China; Department of Gastroenterology, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu 610014, Sichuan, China.
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610064, China; Sichuan Testing Centre for Biomaterials and Medical Devices, Chengdu, Sichuan 610064, China.
出版信息
Biomater Adv. 2023 Mar;146:213286. doi: 10.1016/j.bioadv.2023.213286. Epub 2023 Jan 13.
Endoscopic submucosal dissection (ESD) is a challenging procedure. The use of biomaterials to improve the operator's convenience (operating affinity) has received little attention. We prepared two thermosensitive hydrogels, lactobionic acid-modified chitosan/chitosan/β-glycerophosphate thermosensitive hydrogel (hydrogel 1) and its lyophilized powders (hydrogel 2), characterized their physicochemical properties and evaluated their performance in ESD experiments on large animals, by comparing with the commonly used normal saline (NS) and glycerin fructose (GF). These hydrogels showed good low-temperature fluidity; their viscosities at 4 °C were 92.2 mPa.s and 26.9 mPa.s, respectively. The hydrogels provided significantly better viscoelastic properties than NS and GF. The relaxation moduli of hydrogels were higher than those of NS and GF when the strains were 1 %, 5 %, and 10 %. The hydrogels can be maintained for seven days, even at pH 1, after which they degrade entirely. In pig model experiments, we performed submucosal injection and ESD procedures in the stomach and esophagus. The cushion height produced by the hydrogels was higher than those of NS and GF 30 min after injection. The ESD operation time for hydrogels was significantly shorter. Postoperative wound observation and histological analysis showed that the hydrogels promoted wound healing. The two hydrogels differed in fluidity, viscoelasticity, and other properties, which makes it possible to select the hydrogels according to the size and location of the lesion during ESD operation, and hydrogel 2 may be more suitable for use in lengthier procedures. In general, the hydrogels showed good performance, facilitated the intraoperative operation of ESD, shorten the operation time and promoted wound healing, which is of great significance for reducing the complications and reducing the threshold of ESD operation and further promoting the popularity of ESD.
内镜黏膜下剥离术（ESD）是一项具有挑战性的操作。使用生物材料来提高操作者的便利性（操作亲和力）的方法尚未得到广泛关注。我们制备了两种温敏水凝胶，即乳酰化壳聚糖/壳聚糖/β-甘油磷酸温敏水凝胶（水凝胶 1）及其冻干粉末（水凝胶 2），并对其理化性质进行了表征，通过与常用的生理盐水（NS）和甘油果糖（GF）进行比较，评估了它们在大型动物 ESD 实验中的性能。这些水凝胶表现出良好的低温流动性；其在 4°C 时的粘度分别为 92.2 mPa.s 和 26.9 mPa.s。水凝胶提供了比 NS 和 GF 更好的黏弹性。当应变分别为 1%、5%和 10%时，水凝胶的松弛模量高于 NS 和 GF。即使在 pH 为 1 时，水凝胶也能维持七天的时间，之后完全降解。在猪模型实验中，我们在胃和食管中进行了黏膜下注射和 ESD 操作。注射后 30 分钟，水凝胶产生的垫高度高于 NS 和 GF。水凝胶的 ESD 操作时间明显缩短。术后伤口观察和组织学分析表明，水凝胶促进了伤口愈合。两种水凝胶在流动性、黏弹性和其他性能上存在差异，这使得在 ESD 操作过程中，可以根据病变的大小和位置选择水凝胶，而水凝胶 2 可能更适合用于操作时间较长的手术。总的来说，这些水凝胶表现出良好的性能，有助于 ESD 术中操作，缩短手术时间，促进伤口愈合，这对于减少并发症、降低 ESD 操作门槛和进一步促进 ESD 的普及具有重要意义。
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