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Cardiac Valve Bioreactor for Physiological Conditioning and Hydrodynamic Performance Assessment

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Abstract

Purpose

Tissue engineered heart valves (TEHV) are being investigated to address the limitations of currently available valve prostheses. In order to advance a wide variety of TEHV approaches, the goal of this study was to develop a cardiac valve bioreactor system capable of conditioning living valves with a range of hydrodynamic conditions as well as capable of assessing hydrodynamic performance to ISO 5840 standards.

Methods

A bioreactor system was designed based on the Windkessel approach. Novel features including a purpose-built valve chamber and pressure feedback control were incorporated to maintain asepsis while achieving a range of hydrodynamic conditions. The system was validated by testing hydrodynamic conditions with a bioprosthesis and by operating with cell culture medium for 4 weeks and living cells for 2 weeks.

Results

The bioreactor system was able to produce a range of pressure and flow conditions from static to resting adult left ventricular outflow tract to pathological including hypertension. The system operated aseptically for 4 weeks and cell viability was maintained for 2 weeks. The system was also able to record the pressure and flow data needed to calculate effective orifice area and regurgitant fraction.

Conclusions

We have developed a single bioreactor system that allows for step-wise conditioning protocols to be developed for each unique TEHV design as well as allows for hydrodynamic performance assessment.

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Acknowledgments

The authors gratefully acknowledge Dr. Sorin V. Pislaru, M.D., Ph.D. for assistance with echocardiographic imaging and Drs. Robert T. Tranquillo and Zeeshan Syedain for assistance with pulse duplicator validation.

Conflict of interest

The authors disclose that Harvard Apparatus owns intellectual property filings related to this work with JB, HH, and JC listed as co-inventors. BT, JC, MY, RH, DM, DD, RS, and AL declare that they have no conflict of interest.

Funding

This work was supported by a generous gift from HH Sheikh Hamed Bin Zayed Al-Nahyan and by the NIH (T32 HL007111, K99 HL129068).

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Author information

Correspondence to Amir Lerman.

Additional information

Associate Editor Ajit P. Yoganathan and Jonathan Butcher oversaw the review of this article.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Video 1. Valve functioning in bioreactor. Video taken using the boroscope and digital camera on the outflow side of the tissue valve. (MP4 56125 kb)

Supplementary material 1 (TIFF 1333 kb)

Supplementary material 2 (TIFF 2211 kb)

Video 1. Valve functioning in bioreactor. Video taken using the boroscope and digital camera on the outflow side of the tissue valve. (MP4 56125 kb)

Supplementary material 4 (DOCX 14 kb)

Supplementary material 5 (DOCX 15 kb)

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Tefft, B.J., Choe, J.A., Young, M.D. et al. Cardiac Valve Bioreactor for Physiological Conditioning and Hydrodynamic Performance Assessment. Cardiovasc Eng Tech 10, 80–94 (2019). https://doi.org/10.1007/s13239-018-00382-2

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Keywords

  • Tissue engineered heart valve
  • Biomechanical stimulation
  • Biochemical stimulation
  • Three-dimensional tissue culture
  • ISO 5840