Design and efficacy of a single-use bioreactor for heart valve tissue engineering

Heart valve tissue engineering offers the promise of improved treatments for congenital heart disorders; however, widespread clinical availability of a tissue engineered heart valve (TEHV) has been hindered by scientific and regulatory concerns, including the lack of a disposable, bioreactor system...

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Bibliographic Details
Published in:Journal of biomedical materials research. Part B, Applied biomaterials Applied biomaterials, 2017-02, Vol.105 (2), p.249-259
Main Authors: Converse, Gabriel L, Buse, Eric E, Neill, Kari R, McFall, Christopher R, Lewis, Holley N, VeDepo, Mitchell C, Quinn, Rachael W, Hopkins, Richard A
Format: Article
Language:English
Subjects:
Animals
Aortic Valve
Biomedical materials
Bioprosthesis
Bioreactors
Heart Valve Prosthesis
Humans
Materials research
Materials science
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - metabolism
Sheep
Tissue Engineering - instrumentation
Tissue Engineering - methods
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Summary:Heart valve tissue engineering offers the promise of improved treatments for congenital heart disorders; however, widespread clinical availability of a tissue engineered heart valve (TEHV) has been hindered by scientific and regulatory concerns, including the lack of a disposable, bioreactor system for nondestructive valve seeding and mechanical conditioning. Here we report the design for manufacture and the production of full scale, functional prototypes of such a system. To evaluate the efficacy of this bioreactor as a tool for seeding, ovine aortic valves were decellularized and subjected to seeding with human mesenchymal stem cells (hMSC). The effects of pulsatile conditioning using cyclic waveforms tuned to various negative and positive chamber pressures were evaluated, with respect to the seeding of cells on the decellularized leaflet and the infiltration of seeded cells into the interstitium of the leaflet. Infiltration of hMSCs into the aortic valve leaflet was observed following 72 h of conditioning under negative chamber pressure. Additional conditioning under positive pressure improved cellular infiltration, while retaining gene expression within the MSC-valve interstitial cell phenotype lineage. This protocol resulted in a subsurface pilot population of cells, not full tissue recellularization. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 249-259, 2017.
ISSN:1552-4973
1552-4981
DOI:10.1002/jbm.b.33552