Pediatric tri-tube valved conduits made from fibroblast-produced extracellular matrix evaluated over 52 weeks in growing lambs

Zeeshan H. Syedain, Bee Haynie, Sandra L. Johnson, Matthew Lahti, James Berry, John P. Carney, Jirong Li, Ryan C. Hill, Kirk C. Hansen, Greeshma Thrivikraman, Richard Bianco, Robert T. Tranquillo

Research output: Contribution to journalArticlepeer-review

Abstract

There is a need for replacement heart valves that can grow with children. We fabricated tubes of fibroblast-derived collagenous matrix that have been shown to regenerate and grow as a pulmonary artery replacement in lambs and implemented a design for a valved conduit consisting of three tubes sewn together. Seven lambs were implanted with tri-tube valved conduits in sequential cohorts and compared to bioprosthetic conduits. Valves implanted into the pulmonary artery of two lambs of the first cohort of four animals functioned with mild regurgitation and systolic pressure drops <10 mmHg up to 52 weeks after implantation, during which the valve diameter increased from 19 mm to a physiologically normal ~25 mm. In a second cohort, the valve design was modified to include an additional tube, creating a sleeve around the tri-tube valve to counteract faster root growth relative to the leaflets. Two valves exhibited trivial-to-mild regurgitation at 52 weeks with similar diameter increases to ~25 mm and systolic pressure drops of <5 mmHg, whereas the third valve showed similar findings until moderate regurgitation was observed at 52 weeks, correlating to hyperincrease in the valve diameter. In all explanted valves, the leaflets contained interstitial cells and an endothelium progressing from the base of the leaflets and remained thin and pliable with sparse, punctate microcalcifications. The tri-tube valves demonstrated reduced calcification and improved hemodynamic function compared to clinically used pediatric bioprosthetic valves tested in the same model. This tri-tube valved conduit has potential for long-term valve growth in children.

Original languageEnglish (US)
Article numbereabb7225
JournalScience Translational Medicine
Volume13
Issue number585
DOIs
StatePublished - Mar 17 2021

Bibliographical note

Funding Information:
NIH R01 HL107572 to R.T.T.

Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved.

PubMed: MeSH publication types

  • Journal Article

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