Underwater-adhesive microparticle dressing composed of hydrophobically-modified Alaska pollock gelatin for gastrointestinal tract wound healing
Underwater-adhesive microparticle dressing composed of hydrophobically-modified Alaska pollock gelatin for gastrointestinal tract wound healing
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DOI：
10.1016/j.actbio.2019.08.040
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发表时间：
2019-11-01
影响因子：
9.7
通讯作者：
Taguchi, Tetsushi
中科院分区：
文献类型：
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作者：
Nishiguchi, Akihiro;Kurihara, Yukari;Taguchi, Tetsushi
尽管微创内镜黏膜下剥离术（ESD）成功治疗了早期胃肠道癌，但ESD后仍存在其他症状，包括挛缩、穿孔、出血和食管狭窄。传统的伤口敷料在防止狭窄方面是无效的，因为水下粘合剂在活组织上的稳定性差。在这里，我们提出了一种具有水下粘合稳定性的微粒伤口敷料，用于治疗ESD后的胃肠道伤口愈合。采用明胶在水-乙醇混合溶剂中自组装和热交联的方法制备了疏水改性狭鳕明胶单分散微粒。用脂肪醛对明胶进行疏水改性，通过与活组织的疏水相互作用和内聚力增加明胶对胃和食管粘膜下组织的粘附强度。与未改性的明胶相比，最佳的疏水改性大大提高了微粒的水下稳定性，并在组织上形成了厚的、完整的水凝胶层。对大鼠皮肤创伤愈合模型的组织学观察表明，疏水改性明胶微粒降低了真皮层中α-平滑肌肌动蛋白的表达水平，并且可以抑制ESD后的纤维化和炎症。具有高水下粘附稳定性的微粒伤口敷料具有巨大的治疗潜力，以促进胃肠道伤口愈合，并防止ESD后的其他症状。Statement of Significance本研究的目的是开发具有强组织粘附性的伤口敷料，以促进ESD治疗后的伤口愈合。采用明胶在水-乙醇混合溶剂中自组装和热交联的方法制备了疏水改性狭鳕明胶单分散微粒。用脂肪醛对明胶进行疏水改性，通过与活组织的疏水相互作用和内聚力增强明胶对胃和食管粘膜下组织的粘附强度。最佳的疏水改性大大提高了微粒的水下稳定性。进行了体内研究，以评价这种胶体伤口敷料抑制纤维化的能力。这种新的生物材料具有促进ESD后伤口愈合的巨大潜力。(C)2019 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Despite the success of minimally-invasive endoscopic submucosal dissection (ESD) for the treatment of early gastrointestinal cancer, additional symptoms after ESD, including contracture, perforation, bleeding, and esophageal stricture remain. Conventional wound dressings were ineffective in preventing stricture because of poor stability of underwater-adhesives on living tissues. Here, we present a microparticle-based wound dressing with underwater adhesive stability for the treatment of gastrointestinal tract wound healing after ESD. Monodisperse microparticles composed of hydrophobically-modified Alaska pollock gelatin were prepared by self-assembly of gelatin in water-ethanol mixed solvents and thermal crosslinking. Hydrophobic modification of gelatin with aliphatic aldehydes increased adhesion strength to gastric and esophageal submucosal tissues through hydrophobic interaction with living tissues and cohesion force. Optimal hydrophobic modification drastically improved underwater stability of microparticles compared to that of non-modified gelatin and formed a thick, integrated hydrogel layer on tissues. Histological observation of rat skin wound healing models showed that hydrophobically-modified gelatin microparticles decreased the expression levels of a-smooth muscle actin in the dermis layer and could suppress fibrosis and inflammation after ESD. The microparticle wound dressing with high underwater-adhesive stability has enormous therapeutic potential to promote wound healing in the gastrointestinal tract and prevent additional symptoms after ESD.Statement of SignificanceThe goal of this study was to develop wound dressing with strong tissue-adhesive property to living tissues for promoting wound healing after ESD treatment. Monodisperse microparticles composed of hydrophobically-modified Alaska pollock gelatin were prepared by self-assembly of gelatin in water-ethanol mixed solvents and thermal crosslinking. Hydrophobic modification of gelatin with aliphatic aldehydes enhanced adhesion strength to gastric and esophageal submucosal tissues through hydrophobic interaction with living tissues and cohesion force. Optimal hydrophobic modification drastically improved underwater stability of microparticles. The in vivo studies were performed to evaluate the ability of this colloidal wound dressing to suppress fibrosis. This new biomaterial has enormous potential to promote wound healing after ESD. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.