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Accordion-like honeycombs for tissue engineering of cardiac anisotropy

Abstract

Tissue-engineered grafts may be useful in myocardial repair; however, previous scaffolds have been structurally incompatible with recapitulating cardiac anisotropy. Here, we use microfabrication techniques to create an accordion-like honeycomb microstructure in poly(glycerol sebacate), which yields porous, elastomeric three-dimensional (3D) scaffolds with controllable stiffness and anisotropy. Accordion-like honeycomb scaffolds with cultured neonatal rat heart cells demonstrated utility through: (1) closely matched mechanical properties compared to native adult rat right ventricular myocardium, with stiffnesses controlled by polymer curing time; (2) heart cell contractility inducible by electric field stimulation with directionally dependent electrical excitation thresholds (p<0.05); and (3) greater heart cell alignment (p<0.0001) than isotropic control scaffolds. Prototype bilaminar scaffolds with 3D interconnected pore networks yielded electrically excitable grafts with multi-layered neonatal rat heart cells. Accordion-like honeycombs can thus overcome principal structural–mechanical limitations of previous scaffolds, promoting the formation of grafts with aligned heart cells and mechanical properties more closely resembling native myocardium.

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Figure 1: Structural and mechanical aspects of cardiac anisotropy.
Figure 2: Accordion-like honeycomb scaffolds yield anisotropic mechanical properties similar to native myocardium.
Figure 3: Accordion-like honeycomb scaffolds guide heart cell alignment.
Figure 4: Anisotropic honeycomb scaffolds promote heart cell alignment and directionally dependent electrophysiologic properties.
Figure 5: Prototype bilaminar honeycomb scaffolds with 3D interconnected pore networks are compatible with heart cell cultivation.

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Acknowledgements

Financial support for this work was provided by NIH NRSA fellowship 1 F32 HL084968-01 (to G.C.E.), a Charles Stark Draper fellowship (to C.J.B.), NASA Grant NNJ04HC72G (to L.E.F.) and NIH Grant DE013023 (to R.L.). We are indebted to Y. Wang and M. Radisic for advice on porogen-leached PGS scaffolds, S.N. Bhatia, D. Albright and D. Ward for advice on PGS membrane microfabrication, N. Watson and E. Batchelder for help with confocal and electron microscopy and S. Kangiser for help with manuscript preparation.

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Correspondence to Lisa E. Freed.

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Engelmayr, G., Cheng, M., Bettinger, C. et al. Accordion-like honeycombs for tissue engineering of cardiac anisotropy. Nature Mater 7, 1003–1010 (2008). https://doi.org/10.1038/nmat2316

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