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Evaluation of Bilayer Silk Fibroin Grafts for Tubular Esophagoplasty in a Porcine Defect Model.
Tissue Engineering, Part A ( IF 3.5 ) Pub Date : 2021-01-18 , DOI: 10.1089/ten.tea.2020.0061
Gokhan Gundogdu 1 , Duncan Morhardt 2, 3 , Vivian Cristofaro 3, 4, 5 , Khalid Algarrahi 2, 3 , Xuehui Yang 2, 3 , Kyle Costa 2, 3 , Cinthia Galvez Alegria 2, 3 , Maryrose P Sullivan 3, 4, 5 , Joshua R Mauney 1
Affiliation  

Surgical reconstruction of tubular esophageal defects with autologous gastrointestinal segments is the gold standard treatment to replace damaged or diseased esophageal tissues. Unfortunately, this approach is associated with adverse complications, including dysphagia, donor-site morbidity, and in some cases patient death. Bilayer silk fibroin (BLSF) scaffolds were investigated as alternative, acellular grafts for tubular esophagoplasty in a porcine defect model for 3 months of implantation. Adult Yucatan mini-swine (n = 5) were subjected to esophageal reconstruction with tubular BLSF grafts (2 cm in length) in combination with transient esophageal stenting for 2 months followed by a 1-month period, where the graft site was unstented. All animals receiving BLSF grafts survived and were capable of solid food consumption, however strictures were noted at graft regions in 60% of the experimental cohort between 2 and 3 months postop and required balloon dilation. In addition, fluoroscopic analysis showed peristaltic function in only 1/5 neotissues. Following swine harvest at 3 months, ex vivo tissue bath evaluations revealed that neoconduits exhibited contractile responses to carbachol, electric field stimulation, and KCl, whereas sodium nitroprusside and isoproterenol induced relaxation effects. Histological (Masson's Trichrome) and immunohistochemical analyses of regenerated tissue conduits showed a stratified, squamous epithelium expressing pan-cytokeratins buttressed by a vascularized lamina propria containing a smooth muscle-rich muscularis mucosa surrounded by a muscularis externa. Neuronal density, characterized by the presence of synaptophysin-positive boutons, was significantly lower in neotissues in comparison to nonsurgical controls. BLSF scaffolds represent a promising platform for the repair of tubular esophageal defects, however improvements in scaffold design are needed to reduce the rate of complications and improve the extent of constructive tissue remodeling.

中文翻译:

猪缺损模型中管状食管成形术的双层丝素蛋白移植物的评价。

用自体胃肠段手术重建管状食管缺损是替代受损或患病食管组织的金标准治疗方法。不幸的是,这种方法与不良并发症有关,包括吞咽困难、供体部位发病,在某些情况下甚至导致患者死亡。研究了双层丝素蛋白 (BLSF) 支架作为替代的无细胞移植物,用于猪缺损模型中管状食管成形术的植入期 3 个月。成年尤卡坦小型猪(n  = 5)接受管状 BLSF 移植物(长 2 厘米)结合暂时性食管支架置入术的食道重建,为期 2 个月,然后是 1 个月,移植部位不放置支架。所有接受 BLSF 移植的动物均存活并能够食用固体食物,但在术后 2 至 3 个月内,60% 的实验组动物在移植区域出现狭窄,需要进行球囊扩张。此外,荧光镜分析显示仅 1/5 的新组织具有蠕动功能。3个月收获猪后,体组织浴评估显示,新导管对卡巴胆碱、电场刺激和氯化钾表现出收缩反应,而硝普钠和异丙肾上腺素则诱导松弛作用。再生组织导管的组织学(马森三色)和免疫组织化学分析显示,表达泛细胞角蛋白的分层鳞状上皮由血管化的固有层支撑,固有层包含被外肌层包围的富含平滑肌的肌层粘膜。与非手术对照相比,新组织中的神经元密度(以突触素阳性布顿的存在为特征)显着较低。BLSF 支架代表了修复管状食管缺损的一个有前途的平台,但是需要改进支架设计以降低并发症发生率并提高建设性组织重塑的程度。
更新日期:2021-01-19
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