PDF(Pubmed)
Abstract：
OBJECTIVE: Severe subglottic stenosis develops as a response to intubation in 1% of the >200,000 neonatal intensive care unit infants per year and may require laryngotracheal reconstruction (LTR) with autologous hyaline cartilage. Although effective, LTR is limited by comorbidities, severity of stenosis, and graft integration. In children, there is a significant incidence of restenosis requiring revision surgery. Tissue engineering has been proposed to develop alterative grafting options to improve outcomes and eliminate donor-site morbidity. Our objective is to engineer a decellularized, channel-laden xenogeneic cartilage graft, that we deployed in a proof-of-concept, neonatal porcine LTR model.
METHODS: Meniscal porcine cartilage was freeze-thawed and washed with pepsin/elastase to decellularize and create microchannels. A 6 × 10-mm decellularized cartilage graft was then implanted in 4 infant pigs in an anterior cricoid split. Airway patency and host response were monitored endoscopically until sacrifice at 12 weeks, when the construct phenotype, cricoid expansion, mechanics, and histomorphometry were evaluated.
RESULTS: The selective digestion of meniscal components yielded decellularized cartilage with cell-size channels. After LTR with decellularized meniscus, neonatal pigs were monitored via periodic endoscopy observing re-epithelization, integration, and neocartilage formation. At 12 weeks, the graft appeared integrated and exhibited airway expansion of 4 mm in micro-CT and endoscopy. Micro-CT revealed a larger lumen compared with age-matched controls. Finally, histology showed significant neocartilage formation.
CONCLUSIONS: Our neonatal porcine LTR model with a decellularized cartilage graft is a novel approach to tissue engineered pediatric LTR. This pilot study sets the stage for \"off-the-shelf\" graft procurement and future optimization of MEND for LTR.
METHODS: NA Laryngoscope, 134:807-814, 2024.
METHODS: Meniscal porcine cartilage was freeze-thawed and washed with pepsin/elastase to decellularize and create microchannels. A 6 × 10-mm decellularized cartilage graft was then implanted in 4 infant pigs in an anterior cricoid split. Airway patency and host response were monitored endoscopically until sacrifice at 12 weeks, when the construct phenotype, cricoid expansion, mechanics, and histomorphometry were evaluated.
RESULTS: The selective digestion of meniscal components yielded decellularized cartilage with cell-size channels. After LTR with decellularized meniscus, neonatal pigs were monitored via periodic endoscopy observing re-epithelization, integration, and neocartilage formation. At 12 weeks, the graft appeared integrated and exhibited airway expansion of 4 mm in micro-CT and endoscopy. Micro-CT revealed a larger lumen compared with age-matched controls. Finally, histology showed significant neocartilage formation.
CONCLUSIONS: Our neonatal porcine LTR model with a decellularized cartilage graft is a novel approach to tissue engineered pediatric LTR. This pilot study sets the stage for \"off-the-shelf\" graft procurement and future optimization of MEND for LTR.
METHODS: NA Laryngoscope, 134:807-814, 2024.
摘要：
目的：在每年超过200,000例新生儿重症监护病房的婴儿中，有1%的人发生严重的声门下狭窄是对插管的反应，可能需要用自体透明软骨重建喉气管（LTR）。虽然有效,LTR受到合并症的限制，狭窄的严重程度，和嫁接整合。在儿童中，需要进行翻修手术的再狭窄发生率很高。已提出组织工程来开发替代移植选项，以改善结果并消除供体部位的发病率。我们的目标是设计一个去细胞的,充满通道的异种软骨移植物，我们部署在概念验证中，新生儿猪LTR模型。
方法:将半月板猪软骨冻融并用胃蛋白酶/弹性蛋白酶洗涤以脱细胞并产生微通道。然后将6×10-mm的脱细胞软骨移植物植入4只幼猪的前环状软骨分裂中。通过内窥镜监测气道通畅性和宿主反应，直到12周时处死。当构建体表型，环状突扩张,力学,和组织形态计量学进行了评估。
结果：半月板成分的选择性消化产生了具有细胞大小通道的脱细胞软骨。用去细胞化半月板LTR后，通过定期内窥镜观察新生猪的再上皮化，一体化,和新软骨形成。12周时,在显微CT和内窥镜检查中，移植物出现整合并表现出4mm的气道扩张。与年龄匹配的对照组相比，Micro-CT显示更大的管腔。最后,组织学显示明显的新软骨形成。
结论：我们的带有脱细胞软骨移植物的新生猪LTR模型是一种组织工程儿科LTR的新方法。这项试点研究为“现成的”嫁接采购和未来LTRMEND的优化奠定了基础。
方法：NA喉镜，2023年。
方法:将半月板猪软骨冻融并用胃蛋白酶/弹性蛋白酶洗涤以脱细胞并产生微通道。然后将6×10-mm的脱细胞软骨移植物植入4只幼猪的前环状软骨分裂中。通过内窥镜监测气道通畅性和宿主反应，直到12周时处死。当构建体表型，环状突扩张,力学,和组织形态计量学进行了评估。
结果：半月板成分的选择性消化产生了具有细胞大小通道的脱细胞软骨。用去细胞化半月板LTR后，通过定期内窥镜观察新生猪的再上皮化，一体化,和新软骨形成。12周时,在显微CT和内窥镜检查中，移植物出现整合并表现出4mm的气道扩张。与年龄匹配的对照组相比，Micro-CT显示更大的管腔。最后,组织学显示明显的新软骨形成。
结论：我们的带有脱细胞软骨移植物的新生猪LTR模型是一种组织工程儿科LTR的新方法。这项试点研究为“现成的”嫁接采购和未来LTRMEND的优化奠定了基础。
方法：NA喉镜，2023年。
