Tissue engineered vascular grafts transform into autologous neovessels capable of native function and growth.

Autor: Blum KM; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA.; Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210 USA., Zbinden JC; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA.; Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210 USA., Ramachandra AB; Department of Biomedical Engineering, Yale University, New Haven, CT 06520 USA., Lindsey SE; Department of Pediatrics (Cardiology), Stanford University, Stanford, CA 94305 USA.; Institute for Computational and Mathematical Engineering (ICME), Stanford University, Stanford, CA 94305 USA., Szafron JM; Department of Biomedical Engineering, Yale University, New Haven, CT 06520 USA., Reinhardt JW; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA., Heitkemper M; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA., Best CA; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA.; The Ohio State University College of Medicine, Columbus, OH 43210 USA., Mirhaidari GJM; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA., Chang YC; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA., Ulziibayar A; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA., Kelly J; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA.; The Heart Center, Nationwide Children's Hospital, Columbus, OH 43205 USA., Shah KV; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA., Drews JD; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA.; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA., Zakko J; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA.; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA., Miyamoto S; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA.; Department of Cardiovascular Surgery at Tokyo Women's Medical University, Tokyo, Japan., Matsuzaki Y; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA., Iwaki R; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA., Ahmad H; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA.; Department of Pediatric Colorectal and Pelvic Reconstructive Surgery, Nationwide Children's Hospital, Columbus, OH 43205 USA., Daulton R; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA.; University of Cincinnati College of Medicine 3230 Eden Ave, Cincinnati, OH 45267 USA., Musgrave D; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA., Wiet MG; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA.; The Ohio State University College of Medicine, Columbus, OH 43210 USA., Heuer E; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA., Lawson E; The Ohio State University College of Medicine, Columbus, OH 43210 USA., Schwarz E; Department of Bioengineering, Stanford University, Stanford, CA 94304 USA., McDermott MR; Center for Cardiovascular Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA., Krishnamurthy R; Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio 43205 USA., Krishnamurthy R; Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio 43205 USA., Hor K; The Heart Center, Nationwide Children's Hospital, Columbus, OH 43205 USA., Armstrong AK; The Heart Center, Nationwide Children's Hospital, Columbus, OH 43205 USA., Boe BA; The Heart Center, Nationwide Children's Hospital, Columbus, OH 43205 USA., Berman DP; The Heart Center, Nationwide Children's Hospital, Columbus, OH 43205 USA., Trask AJ; Center for Cardiovascular Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA.; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210 USA., Humphrey JD; Department of Biomedical Engineering, Yale University, New Haven, CT 06520 USA., Marsden AL; Institute for Computational and Mathematical Engineering (ICME), Stanford University, Stanford, CA 94305 USA.; Department of Bioengineering, Stanford University, Stanford, CA 94304 USA., Shinoka T; The Heart Center, Nationwide Children's Hospital, Columbus, OH 43205 USA.; Department of Cardiothoracic Surgery, The Ohio State University College of Medicine, Columbus, OH 43205 USA., Breuer CK; Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 USA.
Jazyk: angličtina
Zdroj: Communications medicine [Commun Med (Lond)] 2022 Jan 10; Vol. 2, pp. 3. Date of Electronic Publication: 2022 Jan 10 (Print Publication: 2022).
DOI: 10.1038/s43856-021-00063-7
Abstrakt: 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.
Competing Interests: Competing interestsGunze Limited, the manufacturer of the scaffold, provided further support for this project to C.K.B. The remaining authors declare no competing interests.
(© The Author(s) 2022.)
Databáze: MEDLINE
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