Elsevier

Biomaterials

Volume 34, Issue 30, October 2013, Pages 7353-7363
Biomaterials

The effect of polymer degradation time on functional outcomes of temporary elastic patch support in ischemic cardiomyopathy

https://doi.org/10.1016/j.biomaterials.2013.06.020Get rights and content

Abstract

Biodegradable polyurethane patches have been applied as temporary mechanical supports to positively alter the remodeling and functional loss following myocardial infarction. How long such materials need to remain in place is unclear. Our objective was to compare the efficacy of porous onlay support patches made from one of three types of biodegradable polyurethane with relatively fast (poly(ester urethane)urea; PEUU), moderate (poly(ester carbonate urethane)urea; PECUU), and slow (poly(carbonate urethane)urea; PCUU) degradation rates in a rat model of ischemic cardiomyopathy. Microporous PEUU, PECUU or PCUU (n = 10 each) patches were implanted over left ventricular lesions 2 wk following myocardial infarction in rat hearts. Infarcted rats without patching and age-matched healthy rats (n = 10 each) were controls. Echocardiography was performed every 4 wk up to 16 wk, at which time hemodynamic and histological assessments were performed. The end-diastolic area for the PEUU group at 12 and 16 wk was significantly larger than for the PECUU or PCUU groups. Histological analysis demonstrated greater vascular density in the infarct region for the PECUU or PCUU versus PEUU group at 16 wk. Improved left ventricular contractility and diastolic performance in the PECUU group was observed at 16 wk compared to infarction controls. The results indicate that the degradation rate of an applied elastic patch influences the functional benefits associated patch placement, with a moderately slow degrading PECUU patch providing improved outcomes.

Introduction

The impairment in cardiac function following myocardial infarction (MI) is typically accompanied by left ventricular (LV) remodeling; a process that includes left ventricular enlargement and changes in chamber geometry [1]. Late post-infarction remodeling involves the LV globally and includes compensatory LV chamber dilatation with time and alterations in LV architecture to distribute the increased wall stresses more evenly [2]. Clinically, it has been reported that survival rate after MI is inversely correlated with severity of LV dilatation [3]. Moreover, LV dilatation can give rise to mitral valve regurgitation by the tethering of chorda tendinea. Thus, therapies designed to attenuate post infarction LV dilatation have been considered to alleviate morbidity and mortality in these patients. Indeed, therapeutic agents, including beta-blockers and angiotensin converting enzyme (ACE) inhibitors, have been reported to act through their effect on remodeling [2], [4].

To directly reduce LV dilatation following MI, surgical ventricular restoration can be applied as a means to reshape the ventricle using a non-elastic, non-degradable endocardial patch (e.g. expanded poly(tetrafluoroethylene)) such as in the Dor or septal anterior ventricular exclusion (SAVE) procedures [5], [6]. Recently, however, the Surgical Treatment for Ischemic Heart failure (STICH) trial demonstrated no benefit in clinical outcome by adding SVR to coronary bypass surgery. This negative outcome has been considered to be attributable to a reduction in diastolic distensibility, thereby impeding LV filling response [1]. Conceptually, an epicardial onlay patch placed onto the infarct lesion has advantages over endocardial patching in that extracorporeal circulation is not required during the procedure, an elastic patch could prevent mechanical compliance mismatch, and such a patch would have the potential to be loaded with cells or bioactive agents should these be deemed necessary. Furthermore, torsion, rotational movement during the cardiac cycle, is greater in the endocardium than the epicardium [7]. Several studies have examined epicardial patch implantation onto the infarcted heart with non-degradable [8], [9] or biodegradable materials [10], [11], [12], [13].

The potential benefits of employing biodegradable materials for an epicardial patch include less risk for infection, host tissue ingrowth, and less adhesion formation. Previously, we have demonstrated temporary mechanical supports with biodegradable polyurethane patches positively alter the remodeling and functional loss following MI in a rat [14] and porcine model [15]. At this time, however, no study has explored how long such materials need to remain in place. In an effort to address the question of patch degradation rate, our objective was to compare the efficacy of porous onlay support patches made from one of three types of biodegradable polyurethane with 1) quicker (poly(ester urethane)urea; PEUU), 2) medium (poly(ester carbonate urethane)urea; PECUU), and 3) slower (poly(ester carbonate)urea; PCUU) degradation rates in a rat model of ischemic cardiomyopathy.

Section snippets

Animal study

Adult female syngeneic Lewis rats (Harlan Sprague Dawley Inc.) 10–12 wk old, weighing 160–210 g were used for this study. The research protocol followed the National Institutes of Health guidelines for animal care and was approved by the Institutional Animal Care and Use Committee of the University of Pittsburgh (#0903312A-3).

Polymer synthesis and scaffold fabrication

PEUU and PCUU were synthesized from soft segments of polycaprolactone (PCL, MW = 2000, Sigma) or poly(hexamethylene carbonate) (PHC, MW = 2000, Sigma) diols respectively,

Material characteristics

All of the fabricated scaffolds were white in color and exhibited a foam-like structure with pore sizes ranging from 75 to 100 μm and a cubic pore shape reflective of the salt crystals used in the processing (Fig. 1). As shown in Table 1, all scaffolds had high distensibility (>100% peak strain) and porosity (>80%), but PEUU scaffolds had significantly greater tensile strength and initial modulus than PECUU and PCUU (n = 4 each scaffold). PECUU and PCUU did not differ in tensile strength and

Discussion

Adverse remodeling of the LV is a compensatory mechanism of chronic ischemic cardiomyopathy, characterized by wall lengthening and thinning, overall ventricular dilatation and geometrical sphericity to maintain cardiac output by increasing stroke volume [28]. This compensatory LV deformation in turn precipitates maladaptive changes in LV structure and function and produces a cycle in which the wall thinning increases end-systolic circumferential and longitudinal wall stresses by LaPlace's law,

Conclusions

The efficacy of porous onlay support patches made from one of three types of biodegradable polyurethane with 1) quicker (poly(ester urethane)urea; PEUU), 2) medium (poly(ester carbonate urethane)urea; PECUU), and 3) slower (poly(ester carbonate)urea; PCUU) degradation rates was compared in a rat model of ischemic cardiomyopathy. The results indicate that the slower degrading patches, and in particular the PECUU polyurethane patch, provided greater benefit in treating ischemic cardiomyopathy

Acknowledgments

Parts of this study were supported by the National Institutes of Health (NIH), BRP (grant# HL069368). The authors thank Atsuko Kido and Deanna L. Rhoads for their excellent help with tissue histological assessment, and Neill J. Turner and Naosumi Sekiya for their expert technical assistance.

References (59)

  • S.K. Brancato et al.

    Wound macrophages as key regulators of repair: origin, phenotype, and function

    Am J Pathol

    (2011)
  • R. Mirza et al.

    Selective and specific macrophage ablation is detrimental to wound healing in mice

    Am J Pathol

    (2009)
  • M.J. van Amerongen et al.

    Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice

    Am J Pathol

    (2007)
  • B.N. Brown et al.

    Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component

    Biomaterials

    (2009)
  • A. Mantovani et al.

    Macrophage polarization comes of age

    Immunity

    (2005)
  • A. Mantovani et al.

    The chemokine system in diverse forms of macrophage activation and polarization

    Trends Immunol

    (2004)
  • N. Sekiya et al.

    Layered implantation of myoblast sheets attenuates adverse cardiac remodeling of the infarcted heart

    J Thorac Cardiovasc Surg

    (2009)
  • R. Hashizume et al.

    Mesenchymal stem cells attenuate angiotensin II-induced aortic aneurysm growth in apolipoprotein E-deficient mice

    J Vasc Surg

    (2011)
  • J. Xiong et al.

    Elastic fibers reconstructed using adenovirus-mediated expression of tropoelastin and tested in the elastase model of abdominal aortic aneurysm in rats

    J Vasc Surg

    (2008)
  • M.A. Dubick et al.

    Elastin metabolism in rodent lung

    Biochim Biophys Acta

    (1981)
  • R.H. Jones et al.

    Coronary bypass surgery with or without surgical ventricular reconstruction

    N Engl J Med

    (2009)
  • M.G. Sutton et al.

    Left ventricular remodeling after myocardial infarction: pathophysiology and therapy

    Circulation

    (2000)
  • H.D. White et al.

    Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction

    Circulation

    (1987)
  • R.N. Doughty et al.

    Effects of carvedilol on left ventricular remodeling after acute myocardial infarction: the CAPRICORN echo substudy

    Circulation

    (2004)
  • V. Dor et al.

    Left ventricular shape changes induced by aneurysmectomy with endoventricular circular patch plasty reconstruction

    Eur Heart J

    (1994)
  • H. Suma et al.

    Role of site selection for left ventriculoplasty to treat idiopathic dilated cardiomyopathy

    Heart Fail Rev

    (2004)
  • M.B. Buchalter et al.

    Noninvasive quantification of left ventricular rotational deformation in normal humans using magnetic resonance imaging myocardial tagging

    Circulation

    (1990)
  • S.T. Kelley et al.

    Restraining infarct expansion preserves left ventricular geometry and function after acute anteroapical infarction

    Circulation

    (1999)
  • K. Matsubayashi et al.

    Improved left ventricular aneurysm repair with bioengineered vascular smooth muscle grafts

    Circulation

    (2003)
  • Cited by (0)

    1

    Present address: Dept. of Pathology and Matrix Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.

    2

    Present address: Dept. Bioengineering, Univ. of Texas at Arlington, Arlington, TX 76019, USA.

    3

    Present address: Department of Plastic and Reconstructive Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

    4

    Present address: Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

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