Biological testing of chitosan-collagen-based porous scaffolds loaded with PLGA/Triamcinolone microspheres for ameliorating endoscopic dissection-related stenosis in oesophagus.

Biological testing of chitosan-collagen-based porous scaffolds loaded with PLGA/Triamcinolone microspheres for ameliorating endoscopic dissection-related stenosis in oesophagus.
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负载PLGA/曲安奈德微球的壳聚糖-胶原基多孔支架用于改善食管内窥镜解剖相关狭窄的生物学测试。

DOI:
10.1111/cpr.13004
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发表时间:
2021-03
期刊:
影响因子:
8.5
通讯作者:
Zhou P
Zhou P
中科院分区:
生物学1区
文献类型:
--
作者:
Ni W;Lin S;Bian S;Xiao M;Wang Y;Yang Y;Lu C;Zheng W;Zhou P

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内镜黏膜下剥离术(ESD)是治疗早期食管肿瘤的首选方法,但不可避免地会导致患者食管狭窄。临床应用糖皮质激素粘膜下注射有利于抑制损伤后食管狭窄,但也存在剂量损失和穿孔等局限性。因此,应开发糖皮质激素治疗的替代品。成功构建了一种新型多孔复合支架ChCo‐TAMS,该支架由壳聚糖、胶原蛋白I和曲安奈德(TA)负载到聚(乳酸-羟基乙酸)(PLGA)微球(TAMS)中组成,并进行了生物学测试,以改善食管ESD相关狭窄。合成的生物材料在抑制巨噬细胞活化、趋化因子介导的细胞募集和成纤维细胞纤维化方面显示出独特的特性。在大鼠皮肤缺损和猪食管ESD模型中的进一步应用表明,这些新型支架在抑制伤口挛缩和食管ESD狭窄方面发挥了强大的作用。开发的复合支架为预防术后食管狭窄提供了一种有前景的临床医疗器械。合成了含有壳聚糖、胶原蛋白和PLGA/曲安奈德微球的复合多孔支架ChCo-TAMS,并用京尼平交联。体外实验表明支架对巨噬细胞活化和肌成纤维细胞转分化具有抑制作用。通过在食管中进行环周ESD建立猪模型,并且通过应用ChCo‐TAMS支架有效地改善术后狭窄。
Endoscopic submucosal dissection (ESD), a preferential approach for early oesophageal neoplasms, inevitably results in oesophageal strictures in patients. Clinical use of glucocorticoids through submucosal injection is beneficial for inhibiting oesophageal stricture following injury; however, it also has limitations, such as dose loss and perforation. Hence, alternatives to glucocorticoid therapy should be developed. A novel porous composite scaffold, ChCo‐TAMS, composed of chitosan, collagen‐I and triamcinolone acetonide (TA) loaded into poly (lactic‐co‐glycolic) acid (PLGA) microspheres (TAMS), was successfully constructed and subjected to biological testing to ameliorate oesophageal ESD‐related stenosis. The synthesized biomaterials displayed unique properties in inhibiting the activation of macrophages, chemokine‐mediated cell recruitment and fibrogenesis of fibroblasts. Further application of the scaffolds in the rat dermal defect and porcine oesophageal ESD model showed that these novel scaffolds played a robust role in inhibiting wound contracture and oesophageal ESD strictures. The developed composite scaffolds provide a promising clinical medical device for the prevention of post‐operative oesophageal stricture. The composite porous scaffold ChCo‐TAMS containing chitosan, collagen and PLGA/Triamcinolone microspheres were synthesized and cross‐linked by genipin. In vitro assays demonstrated the inhibitory effects of the scaffolds upon macrophages activation and myofibroblasts transdifferentiation. The porcine model was established by performing circumferential ESD in oesophagus, and the post‐operative stricture was efficiently ameliorated by application of ChCo‐TAMS scaffolds.
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期刊: Oncotarget
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