An Elastic, Biodegradable Cardiac Patch Induces Contractile Smooth Muscle and Improves Cardiac Remodeling and Function in Subacute Myocardial Infarction
Kazuro L. Fujimoto, MD*, ,
Kimimasa Tobita, MD, , ,
W. David Merryman, PhD,
Jianjun Guan, PhD*,,
Nobuo Momoi, MD, PhD,
Donna B. Stolz, PhD||,
Michael S. Sacks, PhD,,
Bradley B. Keller, MD,,|| and
William R. Wagner, PhD*,,,*
* Department of Surgery, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania
McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania
Department of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania
Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania
|| Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
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Figure 1 Features of PEUU and Representative Images, at 8 Weeks After Implantation
Electron micrograph of the polyester urethane urea (PEUU) material (A). Polyester urethane urea patch in final format (6-mm diameter x 300 µm thick) (B). Representative images, 8 weeks after implantation, of the anterior view of infarction control (C) and PEUU patched (D) hearts. The cross-sectional view of both groups is shown in E and F, respectively. Black arrows point to the implanted PEUU patch, and white arrows indicate the infarcted anterior wall. Scale bar: 500 µm in A, 1 mm in B, 55 mm in C to F. P = the patch implanted area; S = the infarcted scar.
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Figure 2 Representative Histological Sections
Representative histological sections of the infarction control (A) and PEUU patched (B) myocardial wall 8 weeks after implantation stained with hematoxylin and eosin. Black arrows indicate the top of the PEUU implanted area, which appears dark violet. Higher magnification of hematoxylin and eosin staining and immunohistochemical staining appear in C to F where C and D are infarcted control and E and F are PEUU patched.  -SMA staining appears green, CD31 staining appears red, and nuclear staining appears blue. Increased smooth muscle actin is apparent in the PEUU patched group. Scale bars in A and B are 500 µm. For C to F, scale bars are 200 µm.
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Figure 3 Characterization of -SMA–Positive Cells
Smooth muscle myosin heavy chain isotype II (SMMHC-II) (A) immunohistochemical staining colocalized with alpha-smooth muscle actin (-SMA)–positive cells suggesting mature contractile ability. Electron micrographs (B to D) of the muscle-like bundles beneath the polyester urethane urea patch exhibited ultrastructural features typical of mature contractile phenotype smooth muscle cells. White arrow denotes caveole. Black arrow indicates dense bodies. Scale bars for A are 20 µm, for B are 2 µm, and for C and D are 100 nm. My = myofibril; N = nuclear.
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Figure 4 bFGF and VEGF Immunohistochemical Staining
Immunohistochemical staining for basic fibroblast growth factor (bFGF) (A and B) and vascular endothelial growth factor (VEGF) (C and D) in the polyester urethane urea patch (A and C) and infarction control (B and D) groups. The left image of each set shows growth factor and nuclear staining, and the right image merges in alpha-smooth muscle actin (-SMA) staining. Growth factor staining is red, -SMA staining is green, and nuclear staining is blue. Scale bars are 100 µm.
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Figure 5 Echocardiographic Assessment
Echocardiographic assessment of the polyester urethane urea patch, infarction control, and normal control groups during the study period. End-diastolic area is shown in (A), and % fractional area change in (B). End-diastolic area and % fractional area change in the normal control group were significantly different than those in the patch and infarction control groups (p < 0.05) at each time point and did not significantly vary during follow-up. *p < 0.05 between groups; p < 0.05 versus just before implantation (pre) within group. 4w = 4 weeks after implantation; 8w = 8 weeks after implantation.
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Figure 6 Pressure-Strain Relationship for Biomechanical Compliance
Pressure-strain relationship for biomechanical compliance of the left ventricular anterior wall. Circumferential strain (E11) is shown in (A) and longitudinal strain (E22) in (B). For both directions, the infarction control group exhibited the least compliance, while the polyester urethane urea patch group was significantly more compliant, being between infarcted and normal or equivalent to normal tissue.
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