In silico performance of a recellularized tissue-engineered transcatheter aortic valve

Christopher Noble, Joshua Choe, Susheil Uthamaraj, Milton Deherrera, Amir Lerman, Melissa D Young

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Commercially available heart valves have many limitations, such as a lack of remodeling, risk of calcification, and thromboembolic problems. Many state-of-the-art tissueengineered heart valves (TEHV) rely on recellularization to allow remodeling and transition to mechanical behavior of native tissues. Current in vitro testing is insufficient in characterizing a soon-to-be living valve due to this change in mechanical response; thus, it is imperative to understand the performance of an in situ valve. However, due to the complex in vivo environment, this is difficult to accomplish. Finite element (FE) analysis has become a standard tool for modeling mechanical behavior of heart valves; yet, research to date has mostly focused on commercial valves. The purpose of this study has been to evaluate the mechanical behavior of a TEHV material before and after 6 months of implantation in a rat subdermis model. This model allows the recellularization and remodeling potential of the material to be assessed via a simple and inexpensive means prior to more complex ovine orthotropic studies. Biaxial testing was utilized to evaluate the mechanical properties, and subsequently, constitutive model parameters were fit to the data to allow mechanical performance to be evaluated via FE analysis of a full cardiac cycle. Maximum principal stresses and strains from the leaflets and commissures were then analyzed. The results of this study demonstrate that the explanted tissues had reduced mechanical strength compared to the implants but were similar to the native tissues. For the FE models, this trend was continued with similar mechanical behavior in explant and native tissue groups and less compliant behavior in implant tissues. Histology demonstrated recellularization and remodeling although remodeled collagen had no clear directionality. In conclusion, we observed successful recellularization and remodeling of the tissue giving confidence to our TEHV material; however, the mechanical response indicates the additional remodeling would likely occur in the aortic/pulmonary position.

Original languageEnglish (US)
Article number061004
JournalJournal of Biomechanical Engineering
Volume141
Issue number6
DOIs
StatePublished - Jun 1 2019

Fingerprint

Aortic Valve
Computer Simulation
Heart Valves
Tissue
Finite Element Analysis
Finite element method
Histology
Testing
Constitutive models
Collagen
Cooperative Behavior
Strength of materials
Rats
Sheep
Mechanical properties
Lung
Research

Keywords

  • aortic valve simulation
  • finite element analysis
  • recellularization

ASJC Scopus subject areas

  • Biomedical Engineering
  • Physiology (medical)

Cite this

In silico performance of a recellularized tissue-engineered transcatheter aortic valve. / Noble, Christopher; Choe, Joshua; Uthamaraj, Susheil; Deherrera, Milton; Lerman, Amir; Young, Melissa D.

In: Journal of Biomechanical Engineering, Vol. 141, No. 6, 061004, 01.06.2019.

Research output: Contribution to journalArticle

Noble, Christopher ; Choe, Joshua ; Uthamaraj, Susheil ; Deherrera, Milton ; Lerman, Amir ; Young, Melissa D. / In silico performance of a recellularized tissue-engineered transcatheter aortic valve. In: Journal of Biomechanical Engineering. 2019 ; Vol. 141, No. 6.
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abstract = "Commercially available heart valves have many limitations, such as a lack of remodeling, risk of calcification, and thromboembolic problems. Many state-of-the-art tissueengineered heart valves (TEHV) rely on recellularization to allow remodeling and transition to mechanical behavior of native tissues. Current in vitro testing is insufficient in characterizing a soon-to-be living valve due to this change in mechanical response; thus, it is imperative to understand the performance of an in situ valve. However, due to the complex in vivo environment, this is difficult to accomplish. Finite element (FE) analysis has become a standard tool for modeling mechanical behavior of heart valves; yet, research to date has mostly focused on commercial valves. The purpose of this study has been to evaluate the mechanical behavior of a TEHV material before and after 6 months of implantation in a rat subdermis model. This model allows the recellularization and remodeling potential of the material to be assessed via a simple and inexpensive means prior to more complex ovine orthotropic studies. Biaxial testing was utilized to evaluate the mechanical properties, and subsequently, constitutive model parameters were fit to the data to allow mechanical performance to be evaluated via FE analysis of a full cardiac cycle. Maximum principal stresses and strains from the leaflets and commissures were then analyzed. The results of this study demonstrate that the explanted tissues had reduced mechanical strength compared to the implants but were similar to the native tissues. For the FE models, this trend was continued with similar mechanical behavior in explant and native tissue groups and less compliant behavior in implant tissues. Histology demonstrated recellularization and remodeling although remodeled collagen had no clear directionality. In conclusion, we observed successful recellularization and remodeling of the tissue giving confidence to our TEHV material; however, the mechanical response indicates the additional remodeling would likely occur in the aortic/pulmonary position.",
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