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Trilayered tissue construct mimicking the orientations of three layers of a native heart valve leaflet

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Abstract

A tissue-engineered heart valve can be an alternative to a prosthetic valve in heart valve replacement; however, it is not fully efficient in terms of long-lasting functionality, as leaflets in engineered valves do not possess the trilayered native leaflet structure. Previously, we developed a flat, trilayered, oriented nanofibrous (TN) scaffold mimicking the trilayered structure and orientation of native heart valve leaflets. In vivo tissue engineering—a practical regenerative medicine technology—can be used to develop an autologous heart valve. Thus, in this study, we used our flat, trilayered, oriented nanofibrous scaffolds to develop trilayered tissue structures with native leaflet orientations through in vivo tissue engineering in a rat model. After 2 months of in vivo tissue engineering, infiltrated cells and their deposited collagen fibrils were found aligned in the circumferential and radial layers, and randomly oriented in the random layer of the scaffolds, i.e., trilayered tissue constructs (TTCs) were developed. Tensile properties of the TTCs were higher than that of the control tissue constructs (without any scaffolds) due to influence of fibers of the scaffolds in tissue engineering. Different extracellular matrix proteins—collagen, glycosaminoglycans, and elastin—that exist in native leaflets were observed in the TTCs. Gene expression of the TTCs indicated that the tissue constructs were in growing stage. There was no sign of calcification in the tissue constructs. The TTCs developed with the flat TN scaffolds indicate that an autologous leaflet-shaped, trilayered tissue construct that can function as a native leaflet can be developed.

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Acknowledgments

The authors recognize the technical assistance of Dr. Federico Franchi.

Funding

This work is supported by the HH Sheikh Hamed bin Zayed Al Nahyan Program in Biological Valve Engineering and the National Institute of Health (NIH #K99HL134823, # R00HL134823).

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Authors and Affiliations

  1. Department of Bioengineering, University of Missouri, 1406 E Rollins St, Columbia, MO, 65211, USA

    Soumen Jana

  2. Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Soumen Jana & Amir Lerman

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  1. Soumen Jana
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  2. Amir Lerman
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Correspondence to Soumen Jana.

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The authors declare that they have no conflict of interest.

Ethical approval

Implantation and explantation procedures were performed in accordance with authorization and guidelines of the Ethical Committee of Mayo Clinic, Rochester, MN, USA.

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Jana, S., Lerman, A. Trilayered tissue construct mimicking the orientations of three layers of a native heart valve leaflet. Cell Tissue Res 382, 321–335 (2020). https://doi.org/10.1007/s00441-020-03241-6

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