Tissue engineered vascular grafts transform into autologous neovessels capable of native function and growth
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Published:2022-01-10
Issue:1
Volume:2
Page:
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ISSN:2730-664X
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Container-title:Communications Medicine
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language:en
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Short-container-title:Commun Med
Author:
Blum Kevin M., Zbinden Jacob C., Ramachandra Abhay B., Lindsey Stephanie E.ORCID, Szafron Jason M., Reinhardt James W., Heitkemper Megan, Best Cameron A., Mirhaidari Gabriel J. M.ORCID, Chang Yu-Chun, Ulziibayar Anudari, Kelly JohnORCID, Shah Kejal V., Drews Joseph D., Zakko Jason, Miyamoto Shinka, Matsuzaki Yuichi, Iwaki Ryuma, Ahmad HiraORCID, Daulton RobbieORCID, Musgrave Drew, Wiet Matthew G.ORCID, Heuer Eric, Lawson Emily, Schwarz Erica, McDermott Michael R., Krishnamurthy RajeshORCID, Krishnamurthy RamkumarORCID, Hor Kan, Armstrong Aimee K.ORCID, Boe Brian A.ORCID, Berman Darren P., Trask Aaron J., Humphrey Jay D.ORCID, Marsden Alison L., Shinoka ToshiharuORCID, Breuer Christopher K.
Abstract
Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Funder
U.S. Department of Defense U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
Publisher
Springer Science and Business Media LLC
Reference81 articles.
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