A Net Mold-Based Method of Biomaterial-Free Three-Dimensional Cardiac Tissue Creation

Tissue Eng Part C Methods. 2019 Apr;25(4):243-252. doi: 10.1089/ten.TEC.2019.0003.


Ischemic cardiomyopathy poses a significant public health burden due to the irreversible loss of functional cardiac tissue. Alternative treatment strategies include creation of three-dimensional (3D) cardiac tissues to both replace and augment injured native tissue. In this study, we utilize a net mold-based method to create a biomaterial-free 3D cardiac tissue and compare it to current methods using biomaterials. Cardiomyocytes, fibroblasts, and endothelial cells were combined using a hanging drop method to create spheroids. For the net mold patch method, spheroids were seeded into a net mold-based system to create biomaterial-free 3D cardiac patches. For the gel patch, spheroids were embedded in a collagen gel. Immunohistochemistry revealed increased alignment, vascularization, collagen I expression, cell viability, and higher density of cells in the net mold patch compared with the gel patch. Furthermore, in vivo testing in a left anterior descending artery ligation rat model found increased ejection fraction and smaller scar area following implantation of the net mold patch. We present a novel and simple reproducible method to create biomaterial-free 3D net mold patches that may potentially improve the treatment of heart failure in the future.

Keywords: cardiac tissue engineering; hanging drop spheroids; heart failure; mold-based method.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / surgery
  • Biocompatible Materials / pharmacology*
  • Cell Line
  • Cell Size
  • Cell Survival / drug effects
  • Collagen / pharmacology
  • Electrocardiography
  • Exosomes / metabolism
  • Female
  • Heart / diagnostic imaging
  • Heart / drug effects
  • Heart / physiology*
  • Humans
  • Ligation
  • Rats
  • Rats, Inbred Lew
  • Rats, Nude
  • Spheroids, Cellular / cytology
  • Tissue Engineering / methods*


  • Biocompatible Materials
  • Collagen