Tissue-Engineered Myocardial Patch Derived From Extracellular Matrix Provides Regional Mechanical Function

Abstract

Background— Extracellular matrix (ECM), a tissue-engineered scaffold, recently demonstrated cardiomyocyte population after myocardial implantation. Surgical restoration of myocardium frequently uses Dacron as a myocardial patch. We hypothesized that an ECM-derived myocardial patch would provide a mechanical benefit not seen with Dacron. Methods and Results— Using a canine model, a full thickness defect in the right ventricle was repaired with either Dacron or ECM. A third group had no surgery and determined baseline RV function. Eight weeks later, global systolic function was assessed by the preload recruitable stroke work relationship. Regional systolic function was measured by systolic area contraction (SAC), calculated by high density mechanical mapping. Tau was used to assess global diastolic function. Recoil rate and diastolic shear were used as measures of regional diastolic function. After functional data acquisition, tissue was fixed for histological evaluation. Global systolic and diastolic functions were similar at baseline and after ECM and Dacron implantation. Regional systolic function was greater in the ECM group compared with the Dacron group (SAC: 4.1±0.9% versus −1.8±1.1, P <0.05). Regional diastolic function was also greater in the ECM group (recoil rate (° sec −1 ): −44±7 versus −17±2, ECM versus Dacron; P <0.05). Immunohistochemical analysis revealed cardiomyocytes in the ECM implant region, a finding not seen with Dacron. Conclusion— At 8 weeks, an ECM-derived tissue-engineered myocardial patch provides regional mechanical function, likely related to cardiomyocyte population. These results are in sharp contrast to Dacron, a commonly used myocardial patch.

Design of a Fibrin Microthread-Based Composite Layer for Use in a Cardiac Patch

“…31 However, it is critical that resultant patch stiffness remains within the physiological range; too stiff of a patch could induce a tethering effect, inhibiting the contractility of adjacent tissue. 29 Microthreads drawn and stretched in the manner described in this article have a mean wet diameter of 130 ± 22um. 32 Variance in diameter has the potential to create variance in the volume fraction of the fibrin microthreads within a composite material and ultimately the predicted modulus of the composite.…”

“…Upon implantation, it is critical that a cardiac patch be able to mechanically integrate with host myocardium to avoid mechanical mismatch. 4,29 It has also been found that scaffold modulus is an important influence on cardiomyocyte contractile force, phenotype, and gene expression. 4,15,42,43 Using composite theory, we predicted that the trend for doubling fibrin microthread counts from 5 to 10 and from 10 to 20 microthreads should result in a 2-fold increase in scaffold moduli (48 to 95 kPa and 95 to 190 kPa, respectively).…”

“…25 However, hydrogels are typically mechanically weak 26,27 and ultimately may fail in the dynamic loading environment of the heart. 26,28 Thus, it is critical for myocardial regeneration strategies that a cardiac patch be able to mechanically 29 and functionally integrate with native myocardium. 4,8 To achieve this, a cardiac patch should mimic the properties of native myocardium; a highly aligned tissue with modulus values ranging from 20 to 500 kPa.…”

“…Fibrin-based hydrogels have been extensively researched in the field of cardiac engineering, and cell seeded hydrogels have demonstrated functionality such as high twitch forces comparable to the neonatal rat myocardium (8.9 ± 1.1 and 7.8–8.7 mN/mm 2 , respectively) . However, hydrogels are typically mechanically weak , and ultimately may fail in the dynamic loading environment of the heart. , Thus, it is critical for myocardial regeneration strategies that a cardiac patch be able to mechanically and functionally integrate with native myocardium. , To achieve this, a cardiac patch should mimic the properties of native myocardium; a highly aligned tissue with modulus values ranging from 20 to 500 kPa …”

Multimodal biomaterial strategies for regeneration of infarcted myocardium

“…173 Later on, it was shown to be a better alternative in terms of mechanical support, immunogenicity and stiffness to Dacron, a widely used myocardial patch for a variety of diseases. 174 ECM components, such as collagen, tether cardiomyocyte in native heart tissue. Collagen fibres extracted using microbial methods from skeletal tissue are proposed to be suitable patch material since the novel method saves structural deformation of collagen.…”