title: Performance of allogeneic bioengineered replacement pulmonary valves in rapidly growing young lambs.
abstract: Cardiac allometric organ growth after pediatric valve replacement can lead to patient-prosthesis size mismatch and valve re-replacement, which could be mitigated with allogeneic decellularized pulmonary valves treated with collagen conditioning solutions to enhance biological and mechanical performance, termed "bioengineered valves." In this study, we evaluated functional, dimensional, and biological responses of these bioengineered valves compared with traditional cryopreserved valves implanted in lambs during rapid somatic growth.
  
  
  
  From a consanguineous flock of 13 lambs, the pulmonary valves of 10 lambs (mean weight, 19.6 ± 1.4 kg) were replaced with 7 bioengineered valves or 3 classically cryopreserved valves. After 6 months, the 10 lambs with implanted valves and 3 untreated flock mates were compared by echocardiography, cardiac catheterization, and explant pathology.
  
  
  
  Increases in body mass, valve geometric dimensions, and effective orifice areas were similar in the 2 groups of lambs. The bioengineered valves had higher median cusp-to-cusp coaptation areas (34.6%; interquartile range, 21.00%-35.13%) and were more similar to native valves (43.4%; interquartile range, 42.59%-44.01%) compared with cryopreserved valves (13.2%; interquartile range, 7.07%-13.91%) (P = .043). Cryopreserved valves cusps, but not bioengineered valve cusps, were thicker than native valve cusps (P = .01). Histologically, cryopreserved valves demonstrated less than native cellularity, whereas bioengineered valves that were acellular at the time of surgery gained surface endothelium and subsurface myofibroblast interstitial cells in pulmonary artery, sinus wall, and cusp base regions.
  
  
  
  Biological valve conduits can enlarge via passive dilatation without matrix synthesis, but this would result in decreased cusp coaptational areas. Bioengineered valves demonstrated similar annulus enlargement as cryopreserved valves but usually retained larger areas of cuspal coaptation. Heat-shock protein 47-positive (collagen-synthesizing) cells were present in previously acellular bioengineered sinus walls and cusp bases, but rarely in more distal cusp matrices.
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories, Ward Family Heart Center/Cardiothoracic Surgery, Children's Mercy Kansas City, Kansas City, Mo.
authors.forename: Rachael W
authors.initials: RW
authors.lastname: Quinn
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories, Ward Family Heart Center/Cardiothoracic Surgery, Children's Mercy Kansas City, Kansas City, Mo.
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Bert
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories, Ward Family Heart Center/Cardiothoracic Surgery, Children's Mercy Kansas City, Kansas City, Mo.
authors.forename: Gabriel L
authors.initials: GL
authors.lastname: Converse
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories, Ward Family Heart Center/Cardiothoracic Surgery, Children's Mercy Kansas City, Kansas City, Mo.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Buse
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories, Ward Family Heart Center/Cardiothoracic Surgery, Children's Mercy Kansas City, Kansas City, Mo.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hilbert
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories, Ward Family Heart Center/Cardiothoracic Surgery, Children's Mercy Kansas City, Kansas City, Mo.
authors.forename: William B
authors.initials: WB
authors.lastname: Drake
authors.affiliation: Cardiac Regenerative Surgery Research Laboratories, Ward Family Heart Center/Cardiothoracic Surgery, Children's Mercy Kansas City, Kansas City, Mo. Electronic address: rahopkins@cmh.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hopkins
mesh_terms: D064591:Allografts; D000818:Animals; D001021:Aortic Valve; D001705:Bioprosthesis; D002648:Child; D006350:Heart Valve Prosthesis; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D011664:Pulmonary Valve; D012756:Sheep
keywords: allografts; bioengineering; cardiac valve prosthesis; cardiac valves; pulmonary valve; tissue engineering