Carbon-Nanotube-Embedded Hydrogel Sheets for Engineering Cardiac Constructs and Bioactuators

Abstract

We engineered functional cardiac patches by seeding neonatal rat cardiomyocytes onto carbon nanotube (CNT) incorporated photocrosslinkable gelatin methacrylate (GelMA) hydrogel. The resulting cardiac constructs showed excellent mechanical integrity and advanced electrophysiological functions. Specifically, myocardial tissues cultured on 50 μm thick CNT-GelMA showed 3 times higher spontaneous synchronous beating rates and 85% lower excitation threshold, compared to those cultured on pristine GelMA hydrogels. Our results indicate that the electrically conductive and nanofibrous networks formed by CNTs within a porous gelatin framework is the key characteristics of CNT-GelMA leading to improved cardiac cell adhesion, organization, and cell-cell coupling. Centimeter-scale patches were released from glass substrates to form 3D biohybrid actuators, which showed controllable linear cyclic contraction/extension, pumping, and swimming actuations. In addition, we demonstrate for the first time that cardiac tissues cultured on CNT-GelMA resist damage by a model cardiac inhibitor as well as a cytotoxic compound. Therefore, incorporation of CNTs into gelatin, and potentially other biomaterials, could be useful in creating multifunctional cardiac scaffolds for both therapeutic purposes and in vitro studies. These hybrid materials could also be used for neuron and other muscle cells to create tissue constructs with improved organization, electroactivity, and mechanical integrity.

Conductive gelatin methacrylate-poly(aniline) hydrogel for cell encapsulation

“…[4,5] However, the electrically nonconductive nature of hydrogels impedes its use for excitable cells such as neural, skeletal and cardiac muscle, and bone cells. [6,7] To extend the utility of hydrogels, conducting 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 3 elements like metallic nanoparticles [8][9][10][11][12][13][14] and inherently conductive polymers (IHPs) [6,[15][16][17][18][19] have been incorporated within hydrogel matrices in order to add conductive properties to the 3D microenvironments.…”

Fibers for hearts: A critical review on electrospinning for cardiac tissue engineering

“…Carbon nanotubes in general, have been used as additives in several cases to improve the conductivity of polymers, since they show excellent conductive properties and descent biocompatibility [132,133]. Based on these studies Crowder et al proposed the addition of multiwall carbon nanotubes (MWCNTs) in PCL [134].…”

Incorporation of Conductive Materials into Hydrogels for Tissue Engineering Applications

“…As described above, the conductive composites containing CNTs have emerged as functional materials in cardiac tissue engineering. For example, CNTs can be aligned in a gelatin methacryloyl (GelMA) hydrogel by using a dielectriophoresis method [164] that allows the hydrogel to provide accurate and adjustable electrical pulse stimulation to cells and tissues. Mouse embryoid bodies were cultured in microwells containing conductive hydrogels with CNTs.…”