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Quinn R.W.,Cardiac Regenerative Surgery Research Laboratories | Bert A.A.,Cardiac Regenerative Surgery Research Laboratories | Converse G.L.,Cardiac Regenerative Surgery Research Laboratories | Buse E.E.,Cardiac Regenerative Surgery Research Laboratories | And 3 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2016

Background 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. Methods 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. Results 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. Conclusions 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. © 2016 The American Association for Thoracic Surgery


Converse G.L.,Cardiac Regenerative Surgery Research Laboratories | Buse E.E.,Cardiac Regenerative Surgery Research Laboratories | Hopkins R.A.,Cardiac Regenerative Surgery Research Laboratories
Progress in Pediatric Cardiology | Year: 2013

Significant efforts have been made towards the development of a tissue engineered heart valve (TEHV) for the treatment of congenital valvular disorders. While progress has been made, widespread clinical translation of the TEHV has not yet been realized. Regulatory concerns have contributed to this, especially with U.S. markets. The review seeks to identify those challenges, many of which could be mitigated through the implementation of TEHV processing within the clinical environment. However, traditional approaches to heart valve tissue engineering are often not conducive to application in such a setting due to challenges inherent to the seeding strategies themselves, as well as deficiencies in the bioreactor systems used to implement those strategies. Here, we present an alternative strategy that utilizes a novel bioreactor system to circumvent many of the issues that have hindered the translation of the TEHV for the laboratory to bedside. © 2013 Elsevier Ireland Ltd.


PubMed | Cardiac Regenerative Surgery Research Laboratories
Type: Journal Article | Journal: The Journal of thoracic and cardiovascular surgery | Year: 2016

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, 19.61.4kg) were replaced with 7 bioengineered valves or 3 classically cryopreserved valves. After 6months, 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 withoutmatrix 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.

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