CardiacPatch

BMES 212- Body Synthetic, Winter 2008 Project

  • Introduction
  • Problem Statement
  • History
  • Current Research
  • Issues to Address
  • Guestbook
  • Team Members
  •  The Cardiac Patch is a recent innovation and most of the studies on it have been tested only on mice. The studies that have led up to this idea are ones that are involved in putting cells and patches on damaged areas of the heart to try to generate normal heart activity and healing. These studies have been tested on humans as well as other animals.
  •  In a 1992 study on patients with implantable cardioverter defibrillators, epicardial patch electrode patches were sewn on to the epicardial tissue to see if these patches prevented “external transthoracic and internal defibrillation” [1].
  • Numerous synthetic cardiac patches that are inserted onto the damaged region of the heart are also being developed.  For example in a 1995 study, researchers inserted a biodegradable patch made out of a synthetic material called polyhydroxybutyrate onto the pericardium of 50 patients that needed valvular replacement or CABG [4].
  •  Polyhydroxybutyate patches of this type had been previously tested on the hearts of sheep [4].

“Fig 1. Representative images at 12-week explantation for (A) polyester urethane urea and (B) expanded polytetrafluoroethylene; (scale bar, 5 mm)” [7].

  • In 2001 human cell derived Cardiac Patch research was published. In this study angiogenic patches were inserted in infarcted cardiac tissue epicardium [2].

“Fig 2. Representative images at time of explantation (14 days) after injection of TTC. A, Infarct-only treatment group. B, Nonviable 3DFC group. C, Viable 3DFC group. D, Higher magnification of viable 3DFC-treated heart (14 days) demonstrating new vasculature” [5].
  • Human dermal fibroblast cultures (3DFC) were used in a three dimensional epicardial scaffold patch [2].
  • These 3DFC patches are made out of living cells that have growth factors that promote an angiogenic environment [2].
  • These angiogenic promoted factors include formation of capillaries, venules and arteries to the site of the heart with the implanted Cardiac Patch [2].This study was used on mice and they concluded that the 3DFC scaffold could be used in patients with cardiac infarction because the viable cells promote growth and repair factors [2].

“Fig 3. A, H&E histological sections of 14-day heart tissue from control SCID mouse demonstrating normal epicardial and myocardial morphology. B, Infarct-only treatment group. C, Nonviable 3DFC treatment group (suture is visible). D, Viable 3DFC treatment group with new microvessels observed within remodeling cardiac tissue. Microvessels consist of arterioles, capillaries, and venules. E through H, Photographs of H&E sections (E, G) and corresponding serial Gs-1 lectin–reacted sections (F, H) from 30-day viable 3DFC treatment group” [6].

  • In 2005 another study was done with the cardiac patch made out of human dermal fibroblast cultures (3DFC) by the same authors, Kellar et. Al. It was an improvement of the study just discussed [3].
  • This study also tested human dermal fibroblast cultures (3DFC) cells implanted in the epicardium of severe combined immunodeficient (SCID) mice [3].
  • The branch of the left anterior descending (LAD) coronary artery of the mice was blocked to cause damage to the epicardium [3].
  • The angiogenic growth and repair factors secreted from the 3DFC patch were tested to see if the heart healed more compared to the control with no cells implanted into the damaged epicardial region [3].

“Fig.4. Representative gross images in cross-sectional view after explant of (A) normal SCID heart, (B) normal SCID with 3DFC treatment, (C) infarct-only SCID heart, (D) infarcted SCID heart with nonviable 3DFC treatment, and (E) infarcted SCID heart with 3DFC treatment. Scale markings are in millimeters”[8].


  • The left ventricular mechanics of the heart with the Cardiac Patch and without the patch using the Millar conductance catheter system (CCS) was tested [3].
  • The ejection fractions (Efs) and the preload recruitable stroke work (PRSW) parameters were tested as well [3].
  • Kellar et. Al concluded from the results that the 3D human dermal fibroblast cultures (3DFC) were effective in slowing down left ventricle loss of function and this may be due to the patch helping to heal the epicardium of the damaged region of the heart [3].

References


 [1] J. Kemnitz, J. Winter, E.G. Vester and J. Peters, Transcutaneous cardiac pacing in patients with automatic implantable cardioverter defibrillators and epicardial patch electrodes,     Anesthesiology 77 (1992), p. 258

Through sciencedirect:

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B75J3-4GWC57D-J&_user=95578&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000007158&

_version=1&_urlVersion=0&_userid=95578&md5=4134136a7d9ebaf0de4741306b62694c

 [2] Kellar RS, Landeen LK, Shepherd BR, Naughton GK, Ratcliffe A, and Williams SK. Scaffold-based three-dimensional human fibroblast culture provides a structural matrix that supports angiogenesis in infarcted heart tissue. Circulation 104:2063–2068, 2001.

Through American Heart Association:

http://www.circ.ahajournals.org/cgi/content/abstract/104/17/2063

 [3] Kellar Robert, Shepherd Benjamin R., Larson Doug F., Naughton Gail K.,Williams Stuart K. Cardiac Patch Constructed from Human Fibroblasts Attenuates Reduction in Cardiac Function after Acute Infarct. Tissue Engineering. November 1, 2005, 11(11-12): 1678-1687.                    doi:10.1089/ten.2005.11.1678

Through Mary Ann Liebert inc.:

http://www.liebertonline.com/doi/pdf/10.1089/ten.2005.11.1678

    [4] O. Duvernoy, T. Malm, J. Ramstrom and S. Bowald, A biodegradable patch used as a pericardial substitute after cardiac surgery: 6 and 24-month evaluation with CT. Thorac                     Cardiovasc Surg 43 (1995), pp. 271–274.

 [5] Kellar RS, Landeen LK, Shepherd BR, Naughton GK, Ratcliffe A, and Williams SK. Scaffold-based three-dimensional human fibroblast culture provides a structural matrix that supports angiogenesis in infarcted heart tissue. Circulation 104:2063–2068, 2001.  Picture of hearts: http://www.circ.ahajournals.org/cgi/content/full/104/17/2063/FIG1

 [6] Kellar RS, Landeen LK, Shepherd BR, Naughton GK, Ratcliffe A, and Williams SK. Scaffold-based three-dimensional human fibroblast culture provides a structural matrix that supports angiogenesis in infarcted heart tissue. Circulation 104:2063–2068, 2001.  Picture of histology: http://www.circ.ahajournals.org/cgi/content/full/104/17/2063/FIG2

 [7] O. Duvernoy, T. Malm, J. Ramstrom and S. Bowald, A biodegradable patch used as a pericardial substitute after cardiac surgery: 6 and 24-month evaluation with CT. Thorac Cardiovasc Surg 43 (1995), pp. 271–274. Picture of heart: http://www.sciencedirect.com/science?_ob=MiamiCaptionURL&_method=retrieve&_udi=B6T11-4MWPM77-20&_image=fig2&_ba=2&_user=95578&_coverDate=02%2F28%2F2007

&_rdoc=1&_fmt=full&_orig=search&view=c&_acct=C000007158&_version=1&_urlVersion=0&_userid=95578&md5=39f4ee2cb6b67c259978a5b219328577

    [8] Kellar Robert, Shepherd Benjamin R., Larson Doug F., Naughton Gail K.,Williams Stuart K. Cardiac Patch Constructed from Human Fibroblasts Attenuates Reduction in Cardiac                  Function after Acute Infarct. Tissue Engineering. November 1, 2005, 11(11-12): 1678-1687. doi:10.1089/ten.2005.11.1678 

    Picture of hearts: http://www.liebertonline.com/doi/pdf/10.1089/ten.2005.11.1678






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