Three-Dimensional High Resolution Scaffold Fiber Architecture and Morphology in Tissue Engineered Heart Valve Tissue

Engineered heart valve tissue (EHVT) has received much attention as a potential pediatric valve replacement therapy, offering prospective long-term functional improvements over current options. A significant gap in the literature exists, however, regarding estimating tissue mechanical properties from tissue-scaffold composites. Detailed three-dimensional structural information prior to implantation (in vitro) and after implantation in (in vivo) is needed for improved modeling of tissue properties. As such, a novel high-resolution imaging technique will be employed to obtain three-dimensional microstructural information. Analysis techniques will be used to fully quantify constituents of interest including scaffold, collagen, and cellular information and to develop appropriate two-dimensional sectioning sampling protocols. It is the intent of this work to guide modeling efforts to better elucidate EHVT tissue-specific mechanical properties.

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Characterization of three-dimensional anisotropic heart valve tissue mechanical properties using inverse finite element analysis

Journal of the Mechanical Behavior of Biomedical Materials ◽

10.1016/j.jmbbm.2016.04.031 ◽

2016 ◽

Vol 62 ◽

pp. 33-44 ◽

Cited By ~ 20

Author(s):

Mostafa Abbasi ◽

Mohammed S. Barakat ◽

Koohyar Vahidkhah ◽

Ali N. Azadani

Keyword(s):

Mechanical Properties ◽

Finite Element Analysis ◽

Finite Element ◽

Heart Valve ◽

Three Dimensional ◽

Element Analysis ◽

Valve Tissue ◽

Heart Valve Tissue ◽

Inverse Finite Element Analysis

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A Novel Bioreactor for Mechanobiological Studies of Engineered Heart Valve Tissue Formation Under Pulmonary Arterial Physiological Flow Conditions

Journal of Biomechanical Engineering ◽

10.1115/1.4028815 ◽

2014 ◽

Vol 136 (12) ◽

Cited By ~ 23

Author(s):

Sharan Ramaswamy ◽

Steven M. Boronyak ◽

Trung Le ◽

Andrew Holmes ◽

Fotis Sotiropoulos ◽

...

Keyword(s):

Shear Stress ◽

Laminar Flow ◽

Heart Valve ◽

Tissue Formation ◽

Flow Conditions ◽

Physiological Flow ◽

Valve Tissue ◽

Engineered Tissue ◽

Heart Valve Tissue

The ability to replicate physiological hemodynamic conditions during in vitro tissue development has been recognized as an important aspect in the development and in vitro assessment of engineered heart valve tissues. Moreover, we have demonstrated that studies aiming to understand mechanical conditioning require separation of the major heart valve deformation loading modes: flow, stretch, and flexure (FSF) (Sacks et al., 2009, "Bioengineering Challenges for Heart Valve Tissue Engineering," Annu. Rev. Biomed. Eng., 11(1), pp. 289–313). To achieve these goals in a novel bioreactor design, we utilized a cylindrical conduit configuration for the conditioning chamber to allow for higher fluid velocities, translating to higher shear stresses on the in situ tissue specimens while retaining laminar flow conditions. Moving boundary computational fluid dynamic (CFD) simulations were performed to predict the flow field under combined cyclic flexure and steady flow (cyclic-flex-flow) states using various combinations of flow rate, and media viscosity. The device was successfully constructed and tested for incubator housing, gas exchange, and sterility. In addition, we performed a pilot experiment using biodegradable polymer scaffolds seeded with bone marrow derived stem cells (BMSCs) at a seeding density of 5 × 106 cells/cm2. The constructs were subjected to combined cyclic flexure (1 Hz frequency) and steady flow (Re = 1376; flow rate of 1.06 l/min (LPM); shear stress in the range of 0–9 dynes/cm2) for 2 weeks to permit physiological shear stress conditions. Assays revealed significantly (P < 0.05) higher amounts of collagen (2051 ± 256 μg/g) at the end of 2 weeks in comparison to similar experiments previously conducted in our laboratory but performed at subphysiological levels of shear stress (<2 dynes/cm2; Engelmayr et al., 2006, "Cyclic Flexure and Laminar Flow Synergistically Accelerate Mesenchymal Stem Cell-Mediated Engineered Tissue Formation: Implications for Engineered Heart Valve Tissues," Biomaterials, 27(36), pp. 6083–6095). The implications of this novel design are that fully coupled or decoupled physiological flow, flexure, and stretch modes of engineered tissue conditioning investigations can be readily accomplished with the inclusion of this device in experimental protocols on engineered heart valve tissue formation.

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The independent role of cyclic flexure in the early in vitro development of an engineered heart valve tissue

Biomaterials ◽

10.1016/j.biomaterials.2004.02.035 ◽

2005 ◽

Vol 26 (2) ◽

pp. 175-187 ◽

Cited By ~ 116

Author(s):

George C Engelmayr ◽

Elena Rabkin ◽

Fraser W.H Sutherland ◽

Frederick J Schoen ◽

John E Mayer ◽

...

Keyword(s):

Heart Valve ◽

In Vitro Development ◽

Valve Tissue ◽

Heart Valve Tissue ◽

Vitro Development

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The role of organ level conditioning on the promotion of engineered heart valve tissue development in-vitro using mesenchymal stem cells

Biomaterials ◽

10.1016/j.biomaterials.2009.10.019 ◽

2010 ◽

Vol 31 (6) ◽

pp. 1114-1125 ◽

Cited By ~ 66

Author(s):

Sharan Ramaswamy ◽

Danielle Gottlieb ◽

George C. Engelmayr ◽

Elena Aikawa ◽

David E. Schmidt ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Heart Valve ◽

Tissue Development ◽

Valve Tissue ◽

Heart Valve Tissue ◽

Organ Level ◽

Development In Vitro

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In Vitro Hydrodynamic Evaluation of a Scaffold for Heart Valve Tissue Engineering

Artificial Organs ◽

10.1111/aor.13293 ◽

2018 ◽

Vol 43 (2) ◽

pp. 195-198 ◽

Cited By ~ 3

Author(s):

Ovandir Bazan ◽

Márcia M. O. Simbara ◽

Jayme P. Ortiz ◽

Sonia M. Malmonge ◽

Aron Andrade ◽

...

Keyword(s):

Tissue Engineering ◽

Heart Valve ◽

Valve Tissue ◽

Heart Valve Tissue ◽

Heart Valve Tissue Engineering ◽

Hydrodynamic Evaluation

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Flow Patterns in a Flow-Stretch-Flexure Bioreactor System: Implications for the Conditioning of Engineered Heart Valve Tissue

ASME 2009 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2009-206585 ◽

2009 ◽

Cited By ~ 1

Author(s):

Sharan Ramaswamy ◽

David E. Schmidt ◽

Steven M. Boronyak ◽

Michael S. Sacks

Keyword(s):

Heart Valve ◽

Flow Patterns ◽

Tissue Formation ◽

Local Flow ◽

Tissue Scaffold ◽

Mechanical Conditioning ◽

Valve Tissue ◽

Combined Flow ◽

Heart Valve Tissue ◽

Bioreactor System

In heart valve tissue engineering, there is general agreement that appropriate mechanical conditioning may provide the necessary stimuli to promote proper tissue formation [1–3]. For example, in combined flow-flexure-stretch (FSF) studies conducted in our laboratory [4], we demonstrated that flow or flexure bio-mechanical conditioning alone only produced marginally enhanced mass and quality of the engineered tissue. However, combined fluid and flexural stresses resulted in substantially larger de-novo synthesized tissue mass accumulations rates. Interestingly, surface fluid induced stresses acting on the forming tissue/scaffold were the sole difference in the mechanical environment under combined stimulation regimes. However, combined flow and flexural modes of biomechanical conditioning produce highly complex local flow patterns. Understanding these patterns can help identify specific fluid-induced shear characteristics that can potentially be responsible for improving tissue formation in tissue engineered heart valves (TEHVs). In the present study, we developed a computational fluid dynamic (CFD) model to simulate the motion of rectangular scaffold strips housed in the bioreactor. In order to maximize the benefits of flow-based conditioning at physiological scales that emulates the native valve environment, we also present our efforts in designing a new FSF bioreactor system.

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