Biocompatibility evaluation of electrically conductive nanofibrous scaffolds for cardiac tissue engineering.

Myocardial tissue engineering offers a novel technology to improve or regenerate cardiac functions using a combination of cells, biomaterials and engineering strategies. Inspired by low-resistance pathways for electrical signal propagation in the native heart tissue, electrically conductive nanofibrous scaffolds composed of melanin, poly(l-lactide-co-ε-caprolactone) and gelatin were fabricated to provide electrophysiological cues to cardiac myocytes and mimic the native myocardial environment. Our results show that by increasing the concentration of melanin to 40% within the composite, the fiber diameters reduced to 153 ± 30 nm, modulus decreased to 7.1 ± 0.6 MPa, and conductance increased to 259.51 ± 187.60 μS cm-1. Results of cell proliferation and immunostaining analysis of human cardiac myocytes demonstrated that the conductive nanofibers containing 10% melanin promote cell interaction with expression of cardiac-specific proteins compared to other scaffolds. Electrical stimulation through the scaffolds showed enhanced cell proliferation and the expression of connexin-43, signifying the potential of using melanin containing nanofibers as a suitable cardiac patch for the regeneration of infarct myocardium.

[1]  W. Fu,et al.  Preparation and biocompatibility of electrospun poly(l-lactide-co-ɛ-caprolactone)/fibrinogen blended nanofibrous scaffolds , 2011 .

[2]  K. Aslan Rapid Whole Blood Bioassays using Microwave-Accelerated Metal-Enhanced Fluorescence. , 2010, Nano biomedicine and engineering.

[3]  Christine E Schmidt,et al.  Nerve growth factor-immobilized polypyrrole: bioactive electrically conducting polymer for enhanced neurite extension. , 2007, Journal of biomedical materials research. Part A.

[4]  V. Ball,et al.  Protein adsorption on dopamine-melanin films: role of electrostatic interactions inferred from zeta-potential measurements versus chemisorption. , 2010, Journal of colloid and interface science.

[5]  M. Prabhakaran,et al.  Guided orientation of cardiomyocytes on electrospun aligned nanofibers for cardiac tissue engineering. , 2011, Journal of biomedical materials research. Part B, Applied biomaterials.

[6]  P. Riley Molecules in focusMelanin , 1997 .

[7]  D. Seliktar,et al.  Matrix stiffness affects spontaneous contraction of cardiomyocytes cultured within a PEGylated fibrinogen biomaterial. , 2007, Acta biomaterialia.

[8]  W. Blau,et al.  The electrical stimulation of carbon nanotubes to provide a cardiomimetic cue to MSCs. , 2012, Biomaterials.

[9]  Lior Gepstein,et al.  A photopolymerizable hydrogel for 3-D culture of human embryonic stem cell-derived cardiomyocytes and rat neonatal cardiac cells. , 2009, Journal of molecular and cellular cardiology.

[10]  M. Brenner,et al.  Electrospinning and electrically forced jets. I. Stability theory , 2001 .

[11]  Aldo R Boccaccini,et al.  Characterisation of a soft elastomer poly(glycerol sebacate) designed to match the mechanical properties of myocardial tissue. , 2008, Biomaterials.

[12]  Randall J. Lee,et al.  The effect of polypyrrole on arteriogenesis in an acute rat infarct model. , 2008, Biomaterials.

[13]  L. Ghasemi‐Mobarakeh,et al.  Electrical stimulation of nerve cells using conductive nanofibrous scaffolds for nerve tissue engineering. , 2009, Tissue engineering. Part A.

[14]  David J. Mooney,et al.  Non-viral gene delivery regulated by stiffness of cell adhesion substrates , 2005, Nature materials.

[15]  Yen Wei,et al.  Electrospinning polyaniline-contained gelatin nanofibers for tissue engineering applications. , 2006, Biomaterials.

[16]  Jae Young Lee,et al.  Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applications. , 2009, Biomaterials.

[17]  Milica Radisic,et al.  Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[18]  M. Prabhakaran,et al.  Stem cell differentiation to epidermal lineages on electrospun nanofibrous substrates for skin tissue engineering. , 2011, Acta biomaterialia.

[19]  Jin-Ye Wang,et al.  Characterization of nanostructure and cell compatibility of polyaniline films with different dopant acids. , 2008, The journal of physical chemistry. B.

[20]  I. Cianga,et al.  Review paper: Progress in the Field of Conducting Polymers for Tissue Engineering Applications , 2011, Journal of biomaterials applications.

[21]  Lisa E. Freed,et al.  Accordion-Like Honeycombs for Tissue Engineering of Cardiac Anisotropy , 2008, Nature materials.

[22]  Tal Dvir,et al.  Nanowired three dimensional cardiac patches , 2011, Nature nanotechnology.

[23]  Seeram Ramakrishna,et al.  Polypyrrole-contained electrospun conductive nanofibrous membranes for cardiac tissue engineering. , 2011, Journal of biomedical materials research. Part A.

[24]  Kriangsak Ketpang,et al.  Electrospinning PVDF/PPy/MWCNTs conducting composites , 2010 .

[25]  Jonathan W. Valvano,et al.  Electrical Conductivity and Permittivity of Murine Myocardium , 2009, IEEE Transactions on Biomedical Engineering.

[26]  Casey K Chan,et al.  The fabrication of nano-hydroxyapatite on PLGA and PLGA/collagen nanofibrous composite scaffolds and their effects in osteoblastic behavior for bone tissue engineering. , 2009, Bone.

[27]  Seeram Ramakrishna,et al.  Electrospun biocomposite nanofibrous scaffolds for neural tissue engineering. , 2008, Tissue engineering. Part A.

[28]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[29]  A. Epstein,et al.  Polyaniline: conformational changes induced in solution by variation of solvent and doping level , 1995 .

[30]  Robert Langer,et al.  Biocompatibility of biodegradable semiconducting melanin films for nerve tissue engineering. , 2009, Biomaterials.

[31]  Molamma P. Prabhakaran,et al.  Biomimetic material strategies for cardiac tissue engineering , 2011 .

[32]  G G Wallace,et al.  Polypyrrole-heparin composites as stimulus-responsive substrates for endothelial cell growth. , 1999, Journal of biomedical materials research.

[33]  Heungsoo Shin,et al.  The stimulation of myoblast differentiation by electrically conductive sub-micron fibers. , 2009, Biomaterials.

[34]  K. Weber,et al.  Regulation of collagen degradation in the rat myocardium after infarction. , 1995, Journal of molecular and cellular cardiology.

[35]  M. Raghunath,et al.  Evaluation of the Biocompatibility of PLACL/Collagen Nanostructured Matrices with Cardiomyocytes as a Model for the Regeneration of Infarcted Myocardium , 2011 .

[36]  Ze Zhang,et al.  The regulation of cell functions electrically using biodegradable polypyrrole-polylactide conductors. , 2008, Biomaterials.

[37]  Milica Radisic,et al.  Electrical stimulation systems for cardiac tissue engineering , 2009, Nature Protocols.

[38]  N. Kotov,et al.  Melanin-containing films: growth from dopamine solutions versus layer-by-layer deposition. , 2010, Chemphyschem : a European journal of chemical physics and physical chemistry.