Tissue engineered vascular grafts transform into autologous neovessels capable of native function and growth.
Tissue engineered vascular grafts transform into autologous neovessels capable of native function and growth.
复制标题
DOI：
10.1038/s43856-021-00063-7
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Breuer, Christopher K
中科院分区：
文献类型：
--
作者：
Blum, Kevin M;Zbinden, Jacob C;Ramachandra, Abhay B;Lindsey, Stephanie E;Szafron, Jason M;Reinhardt, James W;Heitkemper, Megan;Best, Cameron A;Mirhaidari, Gabriel J M;Chang, Yu-Chun;Ulziibayar, Anudari;Kelly, John;Shah, Kejal V;Drews, Joseph D;Zakko, Jason;Miyamoto, Shinka;Matsuzaki, Yuichi;Iwaki, Ryuma;Ahmad, Hira;Daulton, Robbie;Musgrave, Drew;Wiet, Matthew G;Heuer, Eric;Lawson, Emily;Schwarz, Erica;McDermott, Michael R;Krishnamurthy, Rajesh;Krishnamurthy, Ramkumar;Hor, Kan;Armstrong, Aimee K;Boe, Brian A;Berman, Darren P;Trask, Aaron J;Humphrey, Jay D;Marsden, Alison L;Shinoka, Toshiharu;Breuer, Christopher K
组织工程血管移植物（TEVG）有可能通过创建具有生长能力的功能性血管管道来推进需要先天性心脏病手术的婴儿和儿童的手术管理。在本文中，我们使用了一种综合的计算-实验方法来阐明大型动物临床前模型中新血管形成的自然史;将体外加速降解研究与机械测试、大型动物植入研究与体内成像和组织学以及数据知情的计算生长和重塑模型相结合。我们的研究结果表明，聚合物支架的结构完整性在体内前26周内丢失，而聚合物片段持续长达52周。我们的模型预测，早期新组织积累主要是由炎症过程驱动的，以响应植入的聚合物支架，但随着支架降解，周转变得逐渐机械介导。使用羔羊模型，我们证实，早期新组织形成的结果主要是由支架诱导的异物反应，导致在一个短暂的TEVG狭窄的动态重塑的特点是早期。随着支架降解，机械介导的新组织重塑在26周左右成为主导。在支架完全降解后，所产生的新血管经历生长和重塑，其模仿天然血管行为，包括生物生长能力，进一步得到流体-结构相互作用模拟的支持，提供详细的血液动力学和壁应力信息。这些发现为TEVG重塑提供了见解，并对TEVG在先天性心脏病儿童中的临床应用和未来发展具有重要意义。Blum等人结合联合收割机计算和实验方法，在羔羊模型中研究组织工程血管移植物的长期发展。作者证明，移植物经历生长和重塑，进化以模仿天然血管的特征和功能。外科手术来纠正出生时存在的心脏缺陷，有时需要使用称为血管移植物的人造血管。组织工程血管移植物（TEVG）是一种植入细胞的支架，随着时间的推移，这些细胞可以发育成功能性血管。我们进行了一系列实验室和基于计算机的实验，以研究TEVG如何发育成功能性血管，并证明了植入后TEVG的两个变化阶段：由炎症驱动的早期阶段和由组织的机械特性驱动的后期阶段。在以后的时间点，所产生的血管表现出以与身体自身血管相似的方式生长和响应血流的能力。这些结果提供了对TEVG成为功能性血管的过程的深入了解，并对该技术的未来临床应用产生了影响。
Tissue-engineered vascular grafts (TEVGs) have the potential to advance the surgical management of infants and children requiring congenital heart surgery by creating functional vascular conduits with growth capacity. Herein, we used an integrative computational-experimental approach to elucidate the natural history of neovessel formation in a large animal preclinical model; combining an in vitro accelerated degradation study with mechanical testing, large animal implantation studies with in vivo imaging and histology, and data-informed computational growth and remodeling models. Our findings demonstrate that the structural integrity of the polymeric scaffold is lost over the first 26 weeks in vivo, while polymeric fragments persist for up to 52 weeks. Our models predict that early neotissue accumulation is driven primarily by inflammatory processes in response to the implanted polymeric scaffold, but that turnover becomes progressively mechano-mediated as the scaffold degrades. Using a lamb model, we confirm that early neotissue formation results primarily from the foreign body reaction induced by the scaffold, resulting in an early period of dynamic remodeling characterized by transient TEVG narrowing. As the scaffold degrades, mechano-mediated neotissue remodeling becomes dominant around 26 weeks. After the scaffold degrades completely, the resulting neovessel undergoes growth and remodeling that mimicks native vessel behavior, including biological growth capacity, further supported by fluid–structure interaction simulations providing detailed hemodynamic and wall stress information. These findings provide insights into TEVG remodeling, and have important implications for clinical use and future development of TEVGs for children with congenital heart disease. Blum et al. combine computational and experimental methods to study the long-term development of tissue engineered vascular grafts in a lamb model. The authors demonstrate that the grafts undergo growth and remodeling, evolving to mimic the characteristics and function of a native blood vessel. Surgery to correct defects in the heart that are present at birth sometimes requires the use of artificial blood vessels called vascular grafts. Tissue-engineered vascular grafts (TEVGs) are scaffolds seeded with cells that can develop into functional blood vessels over time. We conducted a series of laboratory and computer-based experiments to investigate how TEVGs develop into functional blood vessels, and demonstrated two phases of changes to the TEVG after implantation: an early phase driven by inflammation, and a later phase driven by the mechanical properties of the tissue. At later time points, the resulting blood vessels demonstrated the ability to grow and respond to blood flow in similar ways to the body’s own blood vessels. These results provide insight into the processes by which TEVGs become functional blood vessels, with implications for future clinical use of this technology.