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原位气管置换小鼠模型中部分脱细胞气管支架的再生

Regeneration of partially decellularized tracheal scaffolds in a mouse model of orthotopic tracheal replacement.

作者信息

Liu Lumei, Dharmadhikari Sayali, Shontz Kimberly M, Tan Zheng Hong, Spector Barak M, Stephens Brooke, Bergman Maxwell, Manning Amy, Zhao Kai, Reynolds Susan D, Breuer Christopher K, Chiang Tendy

机构信息

Center for Regenerative Medicine, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH, USA.

Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH, USA.

出版信息

J Tissue Eng. 2021 Jun 6;12:20417314211017417. doi: 10.1177/20417314211017417. eCollection 2021 Jan-Dec.

Abstract

Decellularized tracheal scaffolds offer a potential solution for the repair of long-segment tracheal defects. However, complete decellularization of trachea is complicated by tracheal collapse. We created a partially decellularized tracheal scaffold (DTS) and characterized regeneration in a mouse model of tracheal transplantation. All cell populations except chondrocytes were eliminated from DTS. DTS maintained graft integrity as well as its predominant extracellular matrix (ECM) proteins. We then assessed the performance of DTS in vivo. Grafts formed a functional epithelium by study endpoint (28 days). While initial chondrocyte viability was low, this was found to improve . We then used atomic force microscopy to quantify micromechanical properties of DTS, demonstrating that orthotopic implantation and graft regeneration lead to the restoration of native tracheal rigidity. We conclude that DTS preserves the cartilage ECM, supports neo-epithelialization, endothelialization and chondrocyte viability, and can serve as a potential solution for long-segment tracheal defects.

摘要

去细胞气管支架为长段气管缺损的修复提供了一种潜在的解决方案。然而,气管的完全去细胞化因气管塌陷而变得复杂。我们创建了一种部分去细胞气管支架(DTS),并在气管移植小鼠模型中对其再生情况进行了表征。除软骨细胞外的所有细胞群都从DTS中被清除。DTS维持了移植物的完整性及其主要的细胞外基质(ECM)蛋白。然后我们评估了DTS在体内的性能。到研究终点(28天)时,移植物形成了功能性上皮。虽然最初软骨细胞的活力较低,但后来发现有所改善。然后我们使用原子力显微镜对DTS的微观力学性能进行量化,结果表明原位植入和移植物再生导致天然气管硬度的恢复。我们得出结论,DTS保留了软骨ECM,支持新上皮化、内皮化和软骨细胞活力,并且可以作为长段气管缺损的一种潜在解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d948/8188978/474679be6c57/10.1177_20417314211017417-fig1.jpg

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