Accordion-like honeycombs for tissue engineering of cardiac anisotropy

• Published in: Nature materials Vol. 7; no. 12; pp. 1003 - 1010
• Main Authors: Freed, Lisa E, Engelmayr, George C, Cheng, Mingyu, Bettinger, Christopher J, Borenstein, Jeffrey T, Langer, Robert
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2008; Nature Publishing Group
• Subjects: Animals; Anisotropy; Biomaterials; Biomechanical Phenomena; Cardiology; Chemistry and Materials Science; Condensed Matter Physics; Curing; Decanoates - chemistry; Electric Conductivity; Electric fields; Glycerol - analogs & derivatives; Glycerol - chemistry; Heart - physiology; Lasers, Excimer; Materials Science; Medical research; Myocardium - cytology; Myocardium - ultrastructure; Nanotechnology; Optical and Electronic Materials; Polymers; Polymers - chemistry; Prototypes; Rats; Rodents; Tissue Engineering; Tissue Scaffolds; Ventricular Function
• ISSN: 1476-1122; 1476-4660
• DOI: 10.1038/nmat2316

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. Construction of tissue-engineering scaffolds that mimic cardiac anisotropy is a challenge. Now, accordion-like honeycomb scaffolds have been created that can form tissue grafts with preferentially aligned heart cells, and with mechanical properties that closely resemble the anisotropy of native myocardium.