Spring-like fibers for cardiac tissue engineering

Abstract

Recapitulation of the cellular microenvironment of the heart, which promotes cell contraction, remains a key challenge in cardiac tissue engineering. We report here on our work, where for the first time, a 3-dimensional (3D) spring-like fiber scaffold was fabricated, successfully mimicking the coiled perimysial fibers of the heart. We hypothesized that since in vivo straightening and re-coiling of these fibers allow stretching and contraction of the myocardium in the direction of the cardiomyocytes, such a scaffold can support the assembly of a functional cardiac tissue capable of generating a strong contraction force. In this study, the mechanical properties of both spring-like single fibers and 3D scaffolds composed of them were investigated. The measurements showed that they have increased elasticity and extensibility compared to corresponding straight fibers and straight fiber scaffolds. We have also shown that cardiac cells cultivated on single spring-like fibers formed cell–fiber interactions that induced fiber stretching in the direction of contraction. Moreover, cardiac cells engineered within 3D thick spring-like fiber scaffolds formed a functional tissue exhibiting significantly improved function, including stronger contraction force (p = 0.002), higher beating rate (p < 0.0001) and lower excitation threshold (p = 0.02), compared to straight fiber scaffolds. Collectively, our results suggest that spring-like fibers can play a key role in contributing to the ex vivo formation of a contracting cardiac muscle tissue. We envision that cardiac tissues engineered within these spring-like fiber scaffolds can be used to improve heart function after infarction.