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基于儿茶酚/硼酸修饰的狭鳕鱼明胶的可注射水凝胶用于内镜黏膜下剥离术的抬举和黏附性能

Elevation and adhesion properties of injectable hydrogels based on catechol/boronic acid-modified Alaska pollock gelatin for endoscopic submucosal dissection.

作者信息

Nagasaka Kazuhiro, Komatsu Hiyori, Ito Shima, Palai Debabrata, Nishiguchi Akihiro, Taguchi Tetsushi

机构信息

Graduate School of Science and Technology, Degree Programs in Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan; Biomaterials Field, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.

Biomaterials Field, Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.

出版信息

Colloids Surf B Biointerfaces. 2025 Jan;245:114307. doi: 10.1016/j.colsurfb.2024.114307. Epub 2024 Oct 9.

Abstract

Elevation of early-stage gastrointestinal cancer using submucosal injection materials (SIMs) and postoperative wound care with adhesive materials are crucial for preventing complications arising from endoscopic submucosal dissection (ESD). Several types of SIMs have been developed; however, they often provide insufficient tissue elevation and fail to adequately adhere to the defect following the removal of early-stage gastrointestinal cancer. In this study, we present the development of injectable Cat-PBA-ApGltn hydrogels, which are based on catechol group-modified Alaska pollock gelatin (Cat-ApGltn) and phenylboronic acid-modified Alaska pollock gelatin (PBA-ApGltn), serving as multifunctional SIMs. A Cat-ApGltn/PBA-ApGltn mixed solution formed a hydrogel within 3 seconds. The resulting Cat-PBA-ApGltn hydrogels were easily injected manually through a 23 G needle due to their shear-thinning properties. Additionally, 10 w/v% Cat-PBA-ApGltn hydrogels demonstrated a 2.3-fold increase in mucosal elevation (7.2 ± 0.4 mm) compared with a commercially available SIM (3.1 ± 0.7 mm). The 10 w/v% Cat-PBA-ApGltn hydrogel, when adhered to porcine gastric submucosa, exhibited a burst strength 7 times greater than the average human intragastric pressure. Furthermore, the Cat-PBA-ApGltn hydrogels demonstrated biodegradability without inducing severe inflammation upon implantation in rat subcutaneous tissue. These Cat-PBA-ApGltn hydrogels hold promise as multifunctional SIMs, boasting injectability, excellent elevation, adhesion capabilities, and biodegradability.

摘要

使用粘膜下注射材料(SIMs)提升早期胃肠道癌以及使用粘合材料进行术后伤口护理对于预防内镜粘膜下剥离术(ESD)引起的并发症至关重要。已经开发了几种类型的SIMs;然而,它们通常提供的组织提升不足,并且在早期胃肠道癌切除后不能充分粘附于缺损处。在本研究中,我们展示了基于儿茶酚基团修饰的狭鳕鱼明胶(Cat-ApGltn)和苯硼酸修饰的狭鳕鱼明胶(PBA-ApGltn)的可注射Cat-PBA-ApGltn水凝胶的开发,其作为多功能SIMs。Cat-ApGltn/PBA-ApGltn混合溶液在3秒内形成水凝胶。由于其剪切变稀特性,所得的Cat-PBA-ApGltn水凝胶很容易通过23G针头手动注射。此外,与市售SIM(3.1±0.7mm)相比,10w/v%的Cat-PBA-ApGltn水凝胶的粘膜提升增加了2.3倍(7.2±0.4mm)。10w/v%的Cat-PBA-ApGltn水凝胶粘附于猪胃粘膜时,其破裂强度比人胃内平均压力大7倍。此外,Cat-PBA-ApGltn水凝胶在植入大鼠皮下组织时表现出生物可降解性,且不会引起严重炎症。这些Cat-PBA-ApGltn水凝胶有望成为多功能SIMs,具有可注射性、出色的提升能力、粘附能力和生物可降解性。

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