Evaluation of Bilayer Silk Fibroin Grafts for Tubular Esophagoplasty in a Porcine Defect Model
Evaluation of Bilayer Silk Fibroin Grafts for Tubular Esophagoplasty in a Porcine Defect Model
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DOI：
10.1089/ten.tea.2020.0061
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发表时间：
2020-06-26
影响因子：
4.1
通讯作者：
Mauney，Joshua R.
中科院分区：
文献类型：
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作者：
Gundogdu，Gokhan;Morhardt，Duncan;Mauney，Joshua R.
以自体胃肠道段重建管状食管状缺损是替代受损或病变食道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、供体部位发病率，在某些情况下还会导致患者死亡。研究了双层丝素蛋白(BLSF)支架作为可替代的无细胞移植物在猪的管状食道成形术中的应用3个月。成年尤卡坦小型猪( )5只，采用管状移植物(长2 cm)与暂时性支架联合重建2个月后1个月，移植物未放置支架。所有接受BLSF移植的动物都存活下来，能够吃固体食物，但60%的实验队列在停药后2-3个月观察到移植物区域狭窄，需要球囊扩张。此外，透视分析显示仅1/5的肿瘤组织有蠕动功能。猪收获3个月后，活体组织浴评估显示，新生导管对卡巴胆碱、电场刺激和KCl有收缩反应，而硝普钠和异丙肾上腺素则有松弛作用。再生组织管道的组织学(Masson‘s trichrome)和免疫组织化学分析显示，表达泛细胞角蛋白的复层鳞状上皮由血管化的固有层支撑，固有层包含富含平滑肌肉的粘膜，周围有外肌。以突触素阳性为特征的神经元密度在肿瘤组织中显著低于非手术对照组。BLSF支架是一种很有前途的修复管状食管状缺损的平台，但支架设计需要改进以减少并发症的发生率和提高建设性组织重建的程度。影响声明寻找一种更好的能够修复管状食道缺损并克服传统自体胃肠段局限性的“现成”支架仍然难以实现。本研究的目的是研究一种脱细胞双层丝素蛋白移植物(BLSF)在猪的管状食道成形术中的性能。我们的结果表明，BLSF支架支持具有神经的、血管化的上皮和肌肉成分的管状肿瘤组织的形成，这些成分能够收缩和松弛反应。BLSF支架是一种很有前途的食道组织工程平台。
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 vivotissue 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.Impact statementThe search for a superior “off-the-shelf” scaffold capable of repairing tubularesophageal defects as well as overcoming limitations associated with conventional autologous gastrointestinal segments remains elusive. The purpose of this study was to investigate the performance of an acellular, bilayer silk fibroin graft (BLSF) for tubular esophagoplasty in a porcine model. Our results demonstrated that BLSF scaffolds supported the formation of tubular neotissues with innervated, vascularized epithelial and muscular components capable of contractile and relaxation responses. BLSF scaffolds represent a promising platform for esophageal tissue engineering.