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Background-Growing evidence suggests that intramyocardial biomaterial injection improves cardiac functions after myocardial infarction (MI) in rodents. Cell therapy is another promising approach to treat MI, although poor retention of transplanted cells is a major challenge. In this study, we hypothesized that intramyocardial injection of self-assembling peptide nanofibers (NFs) thickens the infarcted myocardium and increases transplanted autologous bone marrow mononuclear cell (MNC) retention to attenuate cardiac remodeling and dysfunction in a pig MI model. Methods and Results-A total of 40 mature minipigs were divided into 5 groups: sham, MIϩnormal saline, MIϩNFs, MIϩMNCs, and MIϩMNCs/NFs. MI was induced by coronary occlusion followed by intramyocardial injection of 2 mL normal saline or 1% NFs with or without 1ϫ10 8 isolated autologous MNCs. NF injection significantly improved diastolic function and reduced ventricular remodeling 28 days after treatment. Injection of MNCs alone ameliorated systolic function only, whereas injection of MNCs with NFs significantly improved both systolic and diastolic functions as indicated by ϩdP/dt and ϪdP/dt (1214.5Ϯ91.9 and Ϫ1109.7Ϯ91.2 mm Hg/s in MIϩNS, 1693.7Ϯ84.7 and Ϫ1809.6Ϯ264.3 mm Hg/s in MIϩMNCs/NFs, respectively), increased transplanted cell retention (29.3Ϯ4.5 cells/mm 2 in MIϩMNCs and 229.4Ϯ41.4 cells/mm 2 in MIϩMNCs/NFs) and promoted capillary density in the peri-infarct area. Conclusions-We demonstrated that NF injection alone prevents ventricular remodeling, whereas cell implantation withNFs improves cell retention and cardiac functions after MI in pigs. This unprecedented combined treatment in a large animal model has therapeutic effects, which can be translated to clinical applications in the foreseeable future. (Circulation. 2010; 122[suppl 1]:S132-S141.)Key Words: biomaterials Ⅲ bone marrow mononuclear cells Ⅲ cardiac tissue engineering Ⅲ myocardial infarction C ongestive heart failure is a leading cause of death in the United States and other developed countries. The dominant cause of heart failure is loss of myocardium due to coronary artery disease and the limited regeneration potential of cardiomyocytes. Cardiac tissue engineering is a promising and actively developing area of research aiming to repair, replace, and regenerate the myocardium. Several studies have demonstrated the feasibility of this approach and indicated that direct injection of biomaterials into the infarcted myocardium may be beneficial in preventing deleterious remodeling and reducing cardiac dysfunction. [1][2][3][4] Previous studies using intramyocardial injection of self-assembling peptide nanofibers (NFs), a highly biocompatible 5,6 and biodegradable 7 material, have also revealed their therapeutic potentials for angiogenesis, controlled drug/growth factor release, cell delivery, and stem cell recruitment. [5][6][7][8][9][10] These results indicate that NFs may impact a broad spectrum of applications in myocardial tissue engineering.Cell therapy is another promising approach to h...

An intramyocardial microenvironment was created using nanofibers and VEGF for endogenous cardiac repair after infarction.

Atomic force microscopy provides a novel technique for differentiating the mechanical properties of various cell types. Cell elasticity is abundantly used to represent the structural strength of cells in different conditions. In this study, we are interested in whether physical or physiological cues affect cell elasticity in Atomic force microscopy (AFM)-based assessments. The physical cues include the geometry of the AFM tips, the indenting force and the operating temperature of the AFM. All of these cues show a significant influence on the cell elasticity assessment. Sharp AFM tips create a two-fold increase in the value of the effective Young’s modulus (Eeff) relative to that of the blunt tips. Higher indenting force at the same loading rate generates higher estimated cell elasticity. Increasing the operation temperature of the AFM leads to decreases in the cell stiffness because the structure of actin filaments becomes disorganized. The physiological cues include the presence of fetal bovine serum or extracellular matrix-coated surfaces, the culture passage number, and the culture density. Both fetal bovine serum and the extracellular matrix are critical for cells to maintain the integrity of actin filaments and consequently exhibit higher elasticity. Unlike primary cells, mouse kidney progenitor cells can be passaged and maintain their morphology and elasticity for a very long period without a senescence phenotype. Finally, cell elasticity increases with increasing culture density only in MDCK epithelial cells. In summary, for researchers who use AFM to assess cell elasticity, our results provide basic and significant information about the suitable selection of physical and physiological cues.

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