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Enhanced Autologous Re-endothelialization of Decellularized and Extracellular Matrix Conditioned Allografts Implanted Into the Right Ventricular Outflow Tracts of Juvenile Sheep

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Abstract

Decellularized allografts are promising options for pediatric valve replacement due to reduced immunogenicity and the potential for in vivo autologous recellularization, extracellular matrix (ECM) remodeling and re-endothelialization, which may be enhanced with post-decellularization processing steps. This study investigated the performance and morphology of decellularized and ECM conditioned pulmonary valves implanted in the right ventricular outflow tracts (RVOT) of juvenile sheep. RVOT reconstructions in juvenile sheep using cryopreserved pulmonary allografts (Cryo; n = 2), porcine aortic root bioprostheses (Biopros; n = 2) or decellularized/ECM conditioned pulmonary allografts (Conditioned; n = 4) were performed. Valve performance and morphology were evaluated at 20 weeks after implant. Uniaxial tensile testing was performed on a subset of unimplanted valves from each group. At explant, Biopros had significantly higher peak/mean gradients vs. Conditioned and Cryo, which were similar. No cusp calcification occurred in any valve; arterial wall calcification was present only in Cryo (mild/moderate) and Biopros (severe). No autologous recellularization or inflammation occurred in Biopros; cellularity was decreased in Cryo. Autologous recellularization was present in Conditioned arterial walls and variably extending into the cusps, with consistent cusp re-endothelialization. Conditioned valves had reduced cusp extensibility, increased stiffness and similar tensile strength vs. Cryo. Although Conditioned valves were slightly stiffer and less extensible than Cryo valves, their hemodynamic performance was comparable, indicating they behave as functional heart valves immediately following implant. Because both autologous recellularization and re-endothelialization were seen, ECM conditioning shows promise for encouraging renewal of the cellularity of decellularized allograft valves without the need for pre-implant endothelial cell seeding.

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Acknowledgments

The authors wish to acknowledge the exemplary teamwork and professionalism of the Experimental Cardiac Surgery Team of The Ward Family Center for Congenital Heart Disease: Stacy L. Neighbors, RNFA; Julie Bustamante, RN, CNOR; Jason E. Fenton, RN, MS, CCP; Kellie Merrigan, MPS, CCP.

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Authors and Affiliations

  1. Cardiac Regenerative Surgery Research Laboratories of the Ward Center for Congenital Heart Disease of The Children’s Mercy Hospital, 2401 Gilham Rd., Kansas City, MO, 64108, USA

    Rachael W. Quinn, Stephen L. Hilbert, Gabriel L. Converse, Eric Buse, William B. Drake, Matt Armstrong, Sara J. Moriarty, Gary K. Lofland & Richard A. Hopkins

  2. Department of Surgery (Anesthesiology), The Warren Alpert School of Medicine, Brown University, Providence, RI, USA

    Arthur A. Bert

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  1. Rachael W. Quinn
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Correspondence to Rachael W. Quinn.

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Associate Editor Adrian Chester oversaw the review of this article.

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Quinn, R.W., Hilbert, S.L., Converse, G.L. et al. Enhanced Autologous Re-endothelialization of Decellularized and Extracellular Matrix Conditioned Allografts Implanted Into the Right Ventricular Outflow Tracts of Juvenile Sheep. Cardiovasc Eng Tech 3, 217–227 (2012). https://doi.org/10.1007/s13239-011-0078-y

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