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

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Trilayered tissue construct mimicking the orientations of three layers of a native heart valve leaflet Soumen Jana 1,2 & Amir Lerman 2 Received: 1 May 2019 / Accepted: 11 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

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. Keywords Trilayered . Nanofiber . Scaffold . Cardiac valve leaflet . In vivo tissue engineering

Introduction Heart valve tissue engineering is an alternative to currently available prosthetic heart valves, the mechanical valve and the bioprosthetic valve, for replacement of diseased valves because they face some shortcomings (Cebotari et al. 2006; Gottlieb et al. 2010; Hoerstrup et al. 2000; Jana et al. 2016a). A lifelong anticoagulation medicine is required to prohibit thrombosis caused by mechanical valves (Cannegieter et al. 1994; Hammermeister et al. 1993). Degradation and Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00441-020-03241-6) contains supplementary material, which is available to authorized users. * Soumen Jana [email protected] 1

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

2

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

calcification occur in bioprosthetic valves over passage of time; thus, sequential valve replacements are necessary i