ABSTRACT
Because of the increased use of titanium dioxide (TiO2) nanoparticles (NPs) in tissue engineering (TE), and in new constructs for cardiac TE, their effect was studied on three relevant cell types: Adult rat ventricular cardiomyocytes, human embryonic stem cell-derived cardiomyocytes (hESC-CM) and fibroblasts. For adult rat myocytes, 10 µg/mL TiO2 NPs showed no significant effect on myocyte survival over 24 h or acute myocyte contractility. Increasing the concentration to 100 µg/mL was seen to reduce contraction amplitude (p < 0.05). For hESC-CM, 10 µg/mL TiO2 reduced the beating rate significantly by 24 h. No arrhythmias or cessation of beating were observed in either cell type. Culturing fibroblasts in 5-150 µg/mL TiO2 significantly reduced cell proliferation at day 4 and increased cell death. We conclude that there may be modest but potentially adverse effects of TiO2 NPs if used in fast degrading polymers for myocardial tissue engineering (MTE) applications.
Subject(s)
Metal Nanoparticles/toxicity , Myocardium/cytology , Myocytes, Cardiac/drug effects , Tissue Engineering/methods , Titanium/toxicity , Animals , Cell Line , Cell Proliferation , Cells, Cultured , Electrophysiological Phenomena , L-Lactate Dehydrogenase/metabolism , Metal Nanoparticles/chemistry , Myocytes, Cardiac/physiology , Particle Size , Rats , Rats, Sprague-Dawley , Titanium/chemistryABSTRACT
Grafting of elastomeric biomaterial scaffolds may offer a radical strategy for the prevention of heart failure after myocardial infarction by increasing efficacy of stem cell delivery as well as acting as mechanical restraint devices to constrain scar expansion. Biomaterials can be partially optimized in vitro, but their in vivo performance is most critical and should ideally be monitored serially and noninvasively. We used magnetic resonance imaging (MRI) to assess three scaffold materials with a range of structural moduli equal to or greater than myocardial tissue: poly(glycerol sebacate) (PGS), poly(ethyleneterephathalate)/dimer fatty acid (PED), and TiO(2)-reinforced PED (PED-TiO(2)). Patches, 1 cm in diameter, were grafted onto the hearts of infarcted rats, with biomaterial-free infarcted rat hearts used as controls. MRI was able to determine scaffold size and location on the heart and identified unexpectedly rapid in vivo degradation of the PGS compared with previous in vitro testing. PED patches did not withstand in vivo attachment, but the more rigid PED-TiO(2) material was detrimental to heart function, increasing chamber and scar sizes and reducing ejection fractions compared with controls. In contrast, the mechanically compatible PGS scaffold successfully reduced hypertrophy, giving it potential for limiting excessive postinfarct remodeling. PGS was unable to support systolic function, but it would be suitable for strategies to deliver cardiac stem/progenitor cells, to limit remodeling during the period of functional cellular integration, and to degrade after cell assimilation by the heart. This work has also shown for the first time the value of using MRI as a noninvasive tool for evaluating and optimizing therapeutic biomaterials in vivo.
Subject(s)
Biocompatible Materials/pharmacology , Elastomers/pharmacology , Magnetic Resonance Imaging , Myocardial Infarction/diagnosis , Myocardial Infarction/physiopathology , Tissue Scaffolds/chemistry , Ventricular Remodeling/drug effects , Animals , Disease Models, Animal , Myocardium/pathology , Rats , Tissue EngineeringABSTRACT
INTRODUCTION: Regeneration of the infarcted myocardium after a heart attack is one of the most challenging aspects in tissue engineering. Suitable cell sources and optimized biocompatible materials must be identified. SOURCES OF DATA: In this review, we briefly discuss the current therapeutic options available to patients with heart failure post-myocardial infarction. We describe the various strategies currently proposed to encourage myocardial regeneration, with focus on the achievements in myocardial tissue engineering (MTE). We report on the current cell types, materials and methods being investigated for developing a tissue-engineered myocardial construct. AREAS OF AGREEMENT: Generally, there is agreement that a 'vehicle' is required to transport cells to the infarcted heart to help myocardial repair and regeneration. AREAS OF CONTROVERSY: Suitable cell source, biomaterials, cell environment and implantation time post-infarction remain obstacles in the field of MTE. GROWING POINTS: Research is being focused on optimizing natural and synthetic biomaterials for tissue engineering. The type of cell and its origin (autologous or derived from embryonic stem cells), cell density and method of cell delivery are also being explored. AREAS TIMELY FOR DEVELOPING RESEARCH: The possibility is being explored that materials may not only act as a support for the delivered cell implants, but may also add value by changing cell survival, maturation or integration, or by prevention of mechanical and electrical remodelling of the failing heart.
