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J Thorac Cardiovasc Surg 2008;136:1309-1317
© 2008 The American Association for Thoracic Surgery

Evolving Technology

A fusion protein of hepatocyte growth factor enhances reconstruction of myocardium in a cardiac patch derived from porcine urinary bladder matrix

^a Division of Cardiac Surgery, University of Pittsburgh, Pittsburgh, Pa
^b McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa
^c Cardiovascular Institute, University of Pittsburgh, Pittsburgh, Pa
^d Nano Medical Engineering Laboratory, RIKEN, The Institute of Physical and Chemical Research, Wako, Saitama, Japan
^e Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

Received for publication March 21, 2008; revisions received May 30, 2008; accepted for publication July 4, 2008.

^_* Address for reprints: Marco A. Zenati, MD, Professor of Surgery and Biomedical Engineering, Division of Cardiac Surgery, University of Pittsburgh, 200 Lothrop St, PUH C-700, Pittsburgh, PA 15213. (Email: zenatim{at}upmc.edu).

Objective: We sought to promote myocardial repair using urinary bladder matrix incorporated with a fusion protein that combined hepatocyte growth factor and fibronectin collagen-binding domain in a porcine model. Collagen-binding domain acted as an intermediary to promote hepatocyte growth factor binding and enhance hepatocyte growth factor stability within urinary bladder matrix.

Methods: Urinary bladder matrix incorporated with collagen-binding domain and hepatocyte growth factor was implanted into the porcine right ventricular wall (F group) to repair a surgically created defect. Untreated urinary bladder matrix patches (U group) and Dacron patches (D group) served as controls (N = 5/group). Electromechanical mapping was performed 60 days after surgery. Linear local shortening was used to assess regional contractility, and electrical activity was recorded.

Results: Linear local shortening was significantly improved in the F group compared with controls (F: 0.51% ± 1.57% [P < .05], U: –1.06% ± 1.84%, D: –2.72% ± 2.59%), whereas it was inferior to the normal myocardium (13.7% ± 4.3%; P < .05). Mean electrical activity was 1.49 ± 0.82 mV in the F group, which was statistically greater than in the control groups (U: 0.93 ± 0.71 mV; D: 0.30 ± 0.22 mV; P < .05) and less than the normal myocardium (8.24 ± 2.49 mV; P < .05). Histologic examination showed predominant -smooth muscle actin positive cells with the F group showing the thickest layer and the D group showing the thinnest layer, with an endocardial endothelial monolayer. Scattered isolated islands of -actinin positive cells were observed only in the F group, but not in the controls, suggesting the presence of cardiomyocytes.

Conclusion: The collagen-binding domain/hepatocyte growth factor/urinary bladder matrix patch demonstrated increased contractility and electrical activity compared with urinary bladder matrix alone or Dacron and facilitated a homogeneous repopulation of host cells. Urinary bladder matrix incorporated with collagen-binding domain and hepatocyte growth factor may contribute to constructive myocardial remodeling.