Three-dimensional printed trileaflet valve conduits using biological hydrogels and human valve interstitial cells

Acta Biomater. 2014 May;10(5):1836-46. doi: 10.1016/j.actbio.2013.12.005. Epub 2013 Dec 12.


Tissue engineering has great potential to provide a functional de novo living valve replacement, capable of integration with host tissue and growth. Among various valve conduit fabrication techniques, three-dimensional (3-D) bioprinting enables deposition of cells and hydrogels into 3-D constructs with anatomical geometry and heterogeneous mechanical properties. Successful translation of this approach, however, is constrained by the dearth of printable and biocompatible hydrogel materials. Furthermore, it is not known how human valve cells respond to these printed environments. In this study, 3-D printable formulations of hybrid hydrogels are developed, based on methacrylated hyaluronic acid (Me-HA) and methacrylated gelatin (Me-Gel), and used to bioprint heart valve conduits containing encapsulated human aortic valvular interstitial cells (HAVIC). Increasing Me-Gel concentration resulted in lower stiffness and higher viscosity, facilitated cell spreading, and better maintained HAVIC fibroblastic phenotype. Bioprinting accuracy was dependent upon the relative concentrations of Me-Gel and Me-HA, but when optimized enabled the fabrication of a trileaflet valve shape accurate to the original design. HAVIC encapsulated within bioprinted heart valves maintained high viability, and remodeled the initial matrix by depositing collagen and glyosaminoglycans. These findings represent the first rational design of bioprinted trileaflet valve hydrogels that regulate encapsulated human VIC behavior. The use of anatomically accurate living valve scaffolds through bioprinting may accelerate understanding of physiological valve cell interactions and progress towards de novo living valve replacements.

Keywords: Extracellular matrix; Microenvironment; Rapid prototyping; Remodeling; Tissue engineering.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Aortic Valve / cytology*
  • Aortic Valve / drug effects
  • Blood Vessel Prosthesis*
  • Cattle
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Child
  • Gene Expression Regulation / drug effects
  • Glycosaminoglycans / metabolism
  • Humans
  • Hyaluronic Acid / chemical synthesis
  • Hyaluronic Acid / chemistry
  • Hydrogels / chemical synthesis
  • Hydrogels / chemistry*
  • Immunohistochemistry
  • Methacrylates / chemical synthesis
  • Methacrylates / chemistry
  • Phenotype
  • Real-Time Polymerase Chain Reaction
  • Rheology / drug effects
  • Tissue Engineering / methods*
  • Tissue Scaffolds / chemistry*


  • Glycosaminoglycans
  • Hydrogels
  • Methacrylates
  • Hyaluronic Acid