A three-dimensional in vitro dynamic micro-tissue model of cardiac scar formation

Integr Biol (Camb). 2018 Mar 1;10(3):174-183. doi: 10.1039/c7ib00199a. Epub 2018 Mar 13.


In vitro cardiac models able to mimic the fibrotic process are paramount to develop an effective anti-fibrosis therapy that can regulate fibroblast behaviour upon myocardial injury. In previously developed in vitro models, typical fibrosis features were induced by using scar-like stiffness substrates and/or potent morphogen supplementation in monolayer cultures. In our model, we aimed to mimic in vitro a fibrosis-like environment by applying cyclic stretching of cardiac fibroblasts embedded in three-dimensional fibrin-hydrogels alone. Using a microfluidic device capable of delivering controlled cyclic mechanical stretching (10% strain at 1 Hz), some of the main fibrosis hallmarks were successfully reproduced in 7 days. Cyclic strain indeed increased cell proliferation, extracellular matrix (ECM) deposition (e.g. type-I-collagen, fibronectin) and its stiffness, forming a scar-like tissue with superior quality compared to the supplementation of TGFβ1 alone. Taken together, the observed findings resemble some of the key steps in the formation of a scar: (i) early fibroblast proliferation, (ii) later phenotype switch into myofibroblasts, (iii) ECM deposition and (iv) stiffening. This in vitro scar-on-a-chip model represents a big step forward to investigate the early mechanisms possibly leading later to fibrosis without any possible confounding supplementation of exogenous potent morphogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Proliferation
  • Cicatrix / pathology*
  • Collagen Type I / metabolism
  • Dimethylpolysiloxanes / chemistry
  • Extracellular Matrix / metabolism
  • Fibroblasts / metabolism*
  • Fibronectins / metabolism
  • Fibrosis / pathology
  • Humans
  • Hydrogels
  • In Vitro Techniques
  • Lab-On-A-Chip Devices
  • Microfluidics
  • Myocardial Infarction / pathology
  • Myocardium / metabolism*
  • Myocardium / pathology*
  • Myofibroblasts / metabolism
  • Phenotype
  • Rats
  • Stress, Mechanical
  • Transforming Growth Factor beta1 / metabolism
  • Wound Healing


  • Collagen Type I
  • Dimethylpolysiloxanes
  • Fibronectins
  • Hydrogels
  • Transforming Growth Factor beta1
  • baysilon