Article

Biomimetic perfusion and electrical stimulation applied in concert improved the assembly of engineered cardiac tissue.

Department of Biomedical Engineering, Columbia University, New York, NY, USA.
Journal of Tissue Engineering and Regenerative Medicine (Impact Factor: 4.43). 12/2011; DOI: 10.1002/term.525
Source: PubMed

ABSTRACT Maintenance of normal myocardial function depends intimately on synchronous tissue contraction, driven by electrical activation and on adequate nutrient perfusion in support thereof. Bioreactors have been used to mimic aspects of these factors in vitro to engineer cardiac tissue but, due to design limitations, previous bioreactor systems have yet to simultaneously support nutrient perfusion, electrical stimulation and unconstrained (i.e. not isometric) tissue contraction. To the best of our knowledge, the bioreactor system described herein is the first to integrate these three key factors in concert. We present the design of our bioreactor and characterize its capability in integrated experimental and mathematical modelling studies. We then cultured cardiac cells obtained from neonatal rats in porous, channelled elastomer scaffolds with the simultaneous application of perfusion and electrical stimulation, with controls excluding either one or both of these two conditions. After 8 days of culture, constructs grown with simultaneous perfusion and electrical stimulation exhibited substantially improved functional properties, as evidenced by a significant increase in contraction amplitude (0.23 ± 0.10% vs 0.14 ± 0.05%, 0.13 ± 0.08% or 0.09 ± 0.02% in control constructs grown without stimulation, without perfusion, or either stimulation or perfusion, respectively). Consistently, these constructs had significantly improved DNA contents, cell distribution throughout the scaffold thickness, cardiac protein expression, cell morphology and overall tissue organization compared to control groups. Thus, the simultaneous application of medium perfusion and electrical conditioning enabled by the use of the novel bioreactor system may accelerate the generation of fully functional, clinically sized cardiac tissue constructs. Copyright © 2011 John Wiley & Sons, Ltd.

0 Bookmarks
 · 
163 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bioreactor systems in tissue engineering applications provide various types of stimulation to mimic the tissues in vitro and in vivo. Various bioreactors have been designed to induce high cellular activities, including initial cell attachment, cell growth, and differentiation. Although cell-stimulation processes exert mostly positive effects on cellular responses, in some cases such stimulation can also have a negative effect on cultured cells. In this review, we discuss various types of bioreactor and the positive and negative effects of stimulation (physical, chemical, and electrical) on various cultured cell types. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2014.
    Journal of Biomedical Materials Research Part B Applied Biomaterials 08/2014; · 2.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The vascularization of tissue engineered products represents a key issue in regenerative medicine which needs to be addressed before the translation of these protocols to the bedside can be foreseen. Here we propose a multistep procedure to prepare pre-vascularized three-dimensional (3D) cardiac bio-substitutes using dynamic cell cultures and highly porous biocompatible gelatin scaffolds. The strategy adopted exploits the peculiar differentiation potential of two distinct subsets of adult stem cells to obtain human vascularized 3D cardiac tissues. In the first step of the procedure, human mesenchymal stem cells (hMSCs) are seeded onto gelatin scaffolds to provide interconnected vessel-like structures, while human cardiomyocyte progenitor cells (hCMPCs) are stimulated in vitro to obtain their commitment toward the cardiac phenotype. The use of a modular bioreactor allows the perfusion of the whole scaffold, providing superior performance in terms of cardiac tissue maturation and cell survival. Both the cell culture on natural-derived polymers and the continuous medium perfusion of the scaffold led to the formation of a densely packaged proto-tissue composed of vascular-like and cardiac-like cells, which might complete maturation process and interconnect with native tissue upon in vivo implantation. In conclusion, the data obtained through the approach here proposed highlight the importance to provide stem cells with complementary signals in vitro able to resemble the complexity of cardiac microenvironment.
    Frontiers in physiology. 01/2014; 5:210.
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is significant interest within the tissue engineering and pharmaceutical industries to create 3D microphysiological systems of human organ function. The interest stems from a growing concern that animal models and simple 2D culture systems cannot replicate essential features of human physiology that are critical to predict drug response, or simply to develop new therapeutic strategies to repair or replace damaged organs. Central to human organ function is a microcirculation that not only enhances the rate of nutrient and waste transport by convection, but also provides essential additional physiological functions that can be specific to each organ. This review highlights progress in the creation of in vitro functional microvessel networks, and emphasizes organ-specific functional and structural characteristics that should be considered in the future mimicry of four organ systems that are of primary interest: lung, brain, liver, and muscle (skeletal and cardiac).
    Current opinion in chemical engineering. 02/2014; 3:103-111.

Full-text

Download
43 Downloads
Available from
Jun 10, 2014