CardiacPatch

BMES 212- Body Synthetic, Winter 2008 Project

  • Introduction
  • Problem Statement
  • History
  • Current Research
  • Issues to Address
  • Guestbook
  • Team Members

The Matrix



  • A critical step is the creation of suitable three-dimensional matrices composed of natural or synthetic scaffold  materials that host the cells (defined as cardiac patches), to allow the maintenance of cellular viability and  differentiation and favor cell integration [6]. 
  • For an optimal achievement of cardiac patches, it might be necessary to cultivate three dimensional cell constructs in bioreactors that reproduce the normal stress and flow experienced by the tissues [6]. 

  • Researchers need the ability to carefully  control the culture environment of the cells during heart muscle formation and foster a higher degree of functionality [3].



 The Dimensions


  • Additionally, to envisage the regeneration of the human heart, 1 cm-thick patches of muscular tissue are necessary to achieve successful regeneration[6].
  • Need to engineer heart muscle of any shape or size to match the area of the damaged heart muscle- raising the possibility of engineering customized patched to meet the specific requirements of patients [3].

Fig. 2. A patch of bioreactor grown heart tissue
Credit: L. Freed, G. Vunjak-Novakovic, MIT (Science at Nasa website)
 

The Conditions


  • Clearly, the survival of these patches under the ischaemic conditions present in the injured heart is a major challenge that will have to be addressed. Therefore, the creation of engineered tissue that not only assembles cardiac cells but which also includes factors and/or cells favouring revascularization will be crucial [6].
  • Determining which types of cells hold the most potential, and finding the best way to grow those cells to form viable cardiac tissue that is strong, long-lasting and structured at a cellular level like natural tissue [3].
  • Even if cell-growing conditions can be perfected to produce tissue that is strong, durable and shaped like the native tissue it is designed to replace, another major challenge remains: which type of cells to use. Or more clearly, which types of cells to use - because heart muscle tissue is made up of several types of cells [3].
  • Human heart cells are hard to come by, and "adult" stem cells haven't yet been shown to be changeable into cardiac cells. Embryonic stem cells, while promising, come with political baggage. And other types of muscle cells taken from elsewhere in the body - including skeletal muscles - have been used in early clinical trials, but results are mixed [3]. 
  • Important areas of future work could include optimizing the conditions of electrical stimulation (frequency, field gradient, initiation, and duration of stimulation), quantifying the effect of electrical field stimulation on other cell types present in the native myocardium (endothelial cells and fibroblasts), and testing the biological function and remodeling of the cardiac grafts after implantation in injured myocardium [5].



Implanting


  • Another important point is the possibility to deliver these patches by low-invasive techniques, such as the use of catheters, to avoid thoractomy [6].

 

References

 
[1] Robert S. Kellar, Benjamin R. Shepherd, Doug F. Larson, Gail K. Naughton, Stuart K. Williams. Tissue Engineering. November 1, 2005, 11(11-12): 1678-1687. doi:10.1089/ten.2005.11.1678.
 
http://www.liebertonline.com/doi/abs/10.1089/ten.2005.11.1678?cookieSet=1&journalCode=ten

[2] Paul V. Kochupura, Evren U. Azeloglu, Damon J. Kelly, Sergey V. Doronin, Stephen, F. Badylak, Irvin B. Krukenkamp, Ira S. Cohen and Glenn R. Gaudette. Tissue-Engineered Myocardial Patch Derived From Extracellular Matrix Provides Regional Mechanical Function. Circulation 2005;112;I-144-I-149

http://circ.ahajournals.org/cgi/reprint/112/9_suppl/I-144.pdf

[3] Great Promise in Cardiac Tissue Engineering, But Hurdles Remain Before Lab-grown Muscle Is Ready For Patients.  Article Date: 31 Mar2007 http://www.medicalnewstoday.com/articles/66448.php

[4] Takeyoshi Ota, MD, PhDa, Thomas W. Gilbert, PhDb, Stephen F. Badylak, DVM, MD, PhDb, David Schwartzman, MDc, Marco A. Zenati, MDa,*. Electromechanical characterization of a tissue-engineered myocardial patch derived from extracellular matrix. TISSUE ENGINEERING Volume 11, Number 11/12, 2005

http://jtcs.ctsnetjournals.org/cgi/content/abstract/133/4/979

[5] Milica Radisic*†, Hyoungshin Park*†, Helen Shing‡, Thomas Consi*, Frederick J. Schoen‡, Robert Langer*, Lisa E. Freed*, and Gordana Vunjak-Novakovic*§. Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds. PNAS  December 28, 2004  vol. 101  no. 52  18131

http://www.pnas.org/cgi/content/abstract/0407817101v1

[6] Prisca Zammaretti and Marisa Jaconi. Cardiac tissue engineering: regeneration of the wounded heart. Current Opinion in Biotechnology 2004, 15:430–434

http://www.bioheartinc.com/cte_zammaretti_120304.pdf

 

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