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Non-physiologic Bioreactor Processing Conditions for Heart Valve Tissue Engineering

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Abstract

Purpose

Conventional methods of seeding decellularized heart valves for heart valve tissue engineering have led to inconsistent results in interstitial cellular repopulation, particularly of the distal valve leaflet, and notably distinct from documented re-endothelialization. The use of bioreactor conditioning mimicking physiologic parameters has been well explored but cellular infiltration remains challenging. Non-characteristic, non-physiologic conditioning parameters within a bioreactor, such as hypoxia and cyclic chamber pressure, may be used to increase the cellular infiltration leading to increased recellularization.

Methods

To investigate the effects of novel and perhaps non-intuitive bioreactor conditioning parameters, ovine aortic heart valves were seeded with mesenchymal stem cells and cultured in one of four environments: hypoxia and high cyclic pressures (120 mmHg), normoxia and high cyclic pressures, hypoxia and negative cyclic pressures (− 20 mmHg), and normoxia and negative cyclic pressures. Analysis included measurements of cellular density, cell phenotype, and biochemical concentrations.

Results

The results revealed that the bioreactor conditioning parameters influenced the degree of recellularization. Groups that implemented hypoxic conditioning exhibited increased cellular infiltration into the valve leaflet tissue compared to normoxic conditioning, while pressure conditioning did not have a significant effect of recellularization. Protein expression across all groups was similar, exhibiting a stem cell and valve interstitial cell phenotype. Biochemical analysis of the extracellular matrix was similar between all groups.

Conclusion

These results suggest the use of non-physiologic bioreactor conditioning parameters can increase in vitro recellularization of tissue engineered heart valve leaflets. Particularly, hypoxic culture was found to increase the cellular infiltration. Therefore, bioreactor conditioning of tissue engineered constructs need not always mimic physiologic conditions, and it is worth investigating novel or uncharacteristic culture conditions as they may benefit aspects of tissue culture.

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Conflict of interest

M. VeDepo, E. Buse, A. Paul, G. Converse, and R. Hopkins declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Authors and Affiliations

  1. Cardiac Regenerative Surgery Research Laboratories of The Ward Family Heart Center, Children’s Mercy Kansas City, 2401 Gillham Road, Kansas City, MO, 64108, USA

    Mitchell C. VeDepo, Eric E. Buse, Gabriel L. Converse & Richard A. Hopkins

  2. Bioengineering Program, University of Kansas, 3135A Learned Hall, 1530 W. 15th St, Lawrence, KS, 66045, USA

    Mitchell C. VeDepo & Arghya Paul

  3. BioIntel Research Laboratory, Department of Chemical and Petroleum Engineering, School of Engineering, University of Kansas, Lawrence, KS, 66045, USA

    Arghya Paul

  4. Department of Bioengineering, University of Colorado Anschutz Medical Campus, 12705 E. Montview Blvd. Suite 100, Aurora, CO, 80045-7109, USA

    Mitchell C. VeDepo

Authors
  1. Mitchell C. VeDepo
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  2. Eric E. Buse
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  4. Gabriel L. Converse
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Correspondence to Mitchell C. VeDepo.

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Associate Editor Jane Grande-Allen oversaw the review of this article.

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VeDepo, M.C., Buse, E.E., Paul, A. et al. Non-physiologic Bioreactor Processing Conditions for Heart Valve Tissue Engineering. Cardiovasc Eng Tech 10, 628–637 (2019). https://doi.org/10.1007/s13239-019-00438-x

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  • DOI: https://doi.org/10.1007/s13239-019-00438-x

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