Behavior of valvular interstitial cells on trilayered nanofibrous substrate mimicking morphologies of heart valve leaflet

Research output: Contribution to journalArticle

Abstract

Heart valve tissue engineering could be an alternative to the current bioprosthetic heart valve that faces limitations especially in pediatric patients. However, heart valve tissue engineering has remained challenging because leaflets — the primary component of a heart valve — have three layers with three diverse orientations — circumferential, random and radial, respectively. In order to mimic the orientations, we first designed three novel collectors to fabricate three nanofibrous layers with those orientations from a polymeric biomaterial in an electrospinning system. Then, we devised a novel direct electrospinning technique to develop a unified trilayered nanofibrous (TN) substrate comprising those oriented layers. The TN substrate supported the growth and orientations of seeded porcine valvular interstitial cells (PVICs) and their deposited collagen fibrils. After one month culture, the obtained trilayered tissue construct (TC) exhibited increased tensile properties over its TN substrate. Most importantly, the developed TC did not show any sign of shrinkage. Gene expression pattern of the PVICs indicated the developing stage of the TC. Their protein expression pattern was quite similar to that of leaflets. Statement of Significance: This manuscript talks about development of a novel trilayered nanofibrous substrate mimicking the morphologies of a heart valve leaflet. It also describes culturing of valvular interstitial cells that reside in a leaflet, in the substrate and compares the behavior of the cultured cells with that in native leaflets in terms cell morphology, protein deposition and its orientation, and molecular signature. This study builds the groundwork for our future trilayered, tissue-engineered leaflet development. This research article would be of great interest to investigators and researchers in the field of cardiovascular tissue engineering especially in cardiac valve tissue engineering through biomaterial-based tissue engineering.

LanguageEnglish (US)
Pages142-156
Number of pages15
JournalActa Biomaterialia
Volume85
DOIs
StatePublished - Feb 1 2019

Fingerprint

Heart Valves
Tissue engineering
Tissue Engineering
Cells
Tissue
Substrates
Electrospinning
Biocompatible Materials
Biomaterials
Proteins
Swine
Research Personnel
Pediatrics
Tensile properties
Collagen
Gene expression
Cultured Cells
Gene Expression
Growth
Research

Keywords

  • Cardiac valve leaflet
  • Nanofiber
  • Tissue engineering
  • Trilayered
  • Valvular interstitial cell

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

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title = "Behavior of valvular interstitial cells on trilayered nanofibrous substrate mimicking morphologies of heart valve leaflet",
abstract = "Heart valve tissue engineering could be an alternative to the current bioprosthetic heart valve that faces limitations especially in pediatric patients. However, heart valve tissue engineering has remained challenging because leaflets — the primary component of a heart valve — have three layers with three diverse orientations — circumferential, random and radial, respectively. In order to mimic the orientations, we first designed three novel collectors to fabricate three nanofibrous layers with those orientations from a polymeric biomaterial in an electrospinning system. Then, we devised a novel direct electrospinning technique to develop a unified trilayered nanofibrous (TN) substrate comprising those oriented layers. The TN substrate supported the growth and orientations of seeded porcine valvular interstitial cells (PVICs) and their deposited collagen fibrils. After one month culture, the obtained trilayered tissue construct (TC) exhibited increased tensile properties over its TN substrate. Most importantly, the developed TC did not show any sign of shrinkage. Gene expression pattern of the PVICs indicated the developing stage of the TC. Their protein expression pattern was quite similar to that of leaflets. Statement of Significance: This manuscript talks about development of a novel trilayered nanofibrous substrate mimicking the morphologies of a heart valve leaflet. It also describes culturing of valvular interstitial cells that reside in a leaflet, in the substrate and compares the behavior of the cultured cells with that in native leaflets in terms cell morphology, protein deposition and its orientation, and molecular signature. This study builds the groundwork for our future trilayered, tissue-engineered leaflet development. This research article would be of great interest to investigators and researchers in the field of cardiovascular tissue engineering especially in cardiac valve tissue engineering through biomaterial-based tissue engineering.",
keywords = "Cardiac valve leaflet, Nanofiber, Tissue engineering, Trilayered, Valvular interstitial cell",
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