Abstract
AbstractBiological structures control cell behavior via physical, chemical, electrical, and mechanical cues. Approaches that allow us to build devices that mimic these cues in a combinatorial way are lacking due to there being no suitable instructive materials and limited manufacturing procedures. This challenge is addressed by developing a new conductive composite material, allowing for the fabrication of 3D biomimetic structures in a single manufacturing method based on two‐photon polymerization. The approach induces a combinatorial biostimulative input that can be tailored to a specific application. Development of the 3D architecture is performed with a chemically actuating photocurable acrylate previously identified for cardiomyocyte attachment. The material is made conductive by impregnation with multiwalled carbon nanotubes. The bioinstructive effect of 3D nano‐ and microtopography is combined with electrical stimulation, incorporating biochemical, and electromechanical cues to stimulate cells in serum‐free media. The manufactured architecture is combined with cardiomyocytes derived from human pluripotent stem cells. It is demonstrated that by mimicking biological occurring cues, cardiomyocyte behavior can be modulated. This represents a step change in the ability to manufacture 3D multifunctional biomimetic modulatory architectures. This platform technology has implications in areas spanning regenerative medicine, tissue engineering to biosensing, and may lead to more accurate models for predicting toxicity.
Highlights
Nature constructs microscopic hierarchical cellular machines and architectures or niches that have defined bimolecular, chemical, mechanical, and electrical properties, which provide cues to enable modulation of differentiation and maturation of cells
Cell viability was 54% and 87% on 0.2 wt% and 0.1 wt% multiwalled carbon nanotubes (MWCNTs) composite structures, respectively (Figure 2a). These results indicate that since the DC was low (≈10.5%) for 0.2 wt% compared to 0.1 wt% MWCNTs concentration, the presence of residual monomer and the unreacted PI might have produced cytotoxic effects to the hPSC-CMs, affecting the cell viability
Electrochemical characterization of the composite structures (0.1 wt% MWCNTs) was performed using electrochemical impedance spectroscopy. This revealed an improvement in the electrical conductivity of 2PP fabricated composite structures (Figure 2e) with a reduction in the impedance observed from 1 to 0.6 GΩ and tallies with previous reports of MWCNT based composite materials.[9b,21] The modulus of biomaterials is known to affect the formation of contractile apparatus in hPSC-CMs and in turn, the maturity of the cells.[22]
Summary
Nature constructs microscopic hierarchical cellular machines and architectures or niches that have defined bimolecular, chemical, mechanical, and electrical properties, which provide cues to enable modulation of differentiation and maturation of cells. Electrochemical characterization of the composite structures (0.1 wt% MWCNTs) was performed using electrochemical impedance spectroscopy This revealed an improvement in the electrical conductivity of 2PP fabricated composite structures (Figure 2e) with a reduction in the impedance observed from 1 to 0.6 GΩ and tallies with previous reports of MWCNT based composite materials.[9b,21] The modulus of biomaterials is known to affect the formation of contractile apparatus in hPSC-CMs and in turn, the maturity of the cells.[22] A 68% increase in the modulus (obtained using atomic force microscopy) from 759 ± 22 MPa for PETrA to 989 ± 62 MPa for the composite material with 0.1 wt% MWCNTs was noted, indicating the addition of MWCNTs increased the modulus (Figure 2f)
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