The mechanical environment and anisotropic structure of the heart modulate cardiac function at the cellular, tissue and organ levels. During myocardial infarction (MI) and subsequent healing, however, this landscape changes significantly. In order to engineer cardiac biomaterials with the appropriate properties to enhance function after MI, the changes in the myocardium induced by MI must be clearly identified. In this review, we focus on the mechanical and structural properties of the healthy and infarcted myocardium in order to gain insight about the environment in which biomaterial-based cardiac therapies are expected to perform and the functional deficiencies caused by MI that the therapy must address. From this understanding, we discuss epicardial therapies for MI inspired by the mechanics and anisotropy of the heart focusing on passive devices, which feature a biomaterials approach, and active devices, which feature robotic and cellular components. Through this review, a detailed analysis is provided in order to inspire further development and translation of epicardial therapies for MI.

Mimicking the native three-dimensional microenvironment is of crucial importance when biofabricating a new healthcare material. One aspect of the native tissue that is often omitted when designing a suitable scaffold is its anisotropy. Not only is matching native mechanical properties important when designing implantable scaffolds or healthcare materials, but matching physiological structure is also important as many cell populations respond differently to fiber orientation. Therefore, novel aligned electrospun scaffolds with varying fiber angles and spacing of bundles were created and mechanically characterized. Through controlling the angle between the fibers in each layer of the scaffold, a range of different physiological anisotropic mechanical properties were achieved that encompasses values found in native tissues. Extrapolation of this mechanical data allowed for any native tissue’s anisotropic Young’s modulus to be mimicked by electrospinning fibers at a particular angle. These electrospun scaffolds were then incorporated with cell-laden hydrogels to create hybrid structures that contain the benefits of both scaffolding techniques with the ability to encapsulate cells in the hydrogel. To conclude, this study develops a novel bundled fiber scaffold that was architected to yield anisotropic properties matching native tissues.

Despite numerous advances in treatments for cardiovascular disease, heart failure (HF) remains the leading cause of death worldwide. A significant factor contributing to the progression of cardiovascular diseases into HF is the loss of functioning cardiomyocytes. The recent growth in the field of cardiac tissue engineering has the potential to not only reduce the downstream effects of injured tissues on heart function and longevity but also re-engineer cardiac function through regeneration of contractile tissue. One leading strategy to accomplish this is via a cellularized patch that can be surgically implanted onto a diseased heart. A key area of this field is the use of tissue scaffolds to recapitulate the mechanical and structural environment of the native heart and thus promote engineered myocardium contractility and function. While the strong mechanical properties and anisotropic structural organization of the native heart can be largely attributed to a robust extracellular matrix, similar strength and organization has proven to be difficult to achieve in cultured tissues. Polycaprolactone (PCL) is an emerging contender to fill these gaps in fabricating scaffolds that mimic the mechanics and structure of the native heart. In the field of cardiovascular engineering, PCL has recently begun to be studied as a scaffold for regenerating the myocardium due to its facile fabrication, desirable mechanical, chemical, and biocompatible properties, and perhaps most importantly, biodegradability, which make it suitable for regenerating and re-engineering function to the heart after disease or injury. This review focuses on the application of PCL as a scaffold specifically in myocardium repair and regeneration and outlines current fabrication approaches, properties, and possibilities of PCL incorporation into engineered myocardium, as well as provides suggestions for future directions and a roadmap toward clinical translation of this technology.