Research ArticleTissue Engineering

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

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Science Translational Medicine  17 Mar 2021:
Vol. 13, Issue 585, eabb7225
DOI: 10.1126/scitranslmed.abb7225

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Evaluating engineered valves

Particularly for pediatric patients, replacement heart valves that can grow with the patient would substantially reduce surgical burden. Syedain et al. designed acellular conduits for pulmonary valve replacement by suturing together three tubes of cell-derived extracellular matrix. The valves maintained their function for 52 weeks when implanted in the pulmonary arteries of lambs, and adding an additional tubular sleeve around the tri-tube valve improved the valve design and reduced regurgitation at explantation. Valves became recellularized and increased in diameter over time while showing reduced calcification compared to clinically used bioprosthetic valves, supporting the potential utility of these conduits in pediatric populations.

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.

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