Biomaterializing the promise of cardiac tissue engineering

Abstract

During an average individual's lifespan, the human heart pumps nearly 200 million liters of blood delivered by approximately 3 billion heartbeats. Therefore, it is not surprising that native myocardium under this incredible demand is extraordinarily complex, both structurally and functionally. As a result, successful engineering of adult-mimetic functional cardiac tissues is likely to require utilization of highly specialized biomaterials representative of the native extracellular microenvironment. There is currently no single biomaterial that fully recapitulates the architecture or the biochemical and biomechanical properties of adult myocardium. However, significant effort has gone toward designing highly functional materials and tissue constructs that may one day provide a ready source of cardiac tissue grafts to address the overwhelming burden of cardiomyopathic disease. In the near term, biomaterial-based scaffolds are helping to generate in vitro systems for querying the mechanisms underlying human heart homeostasis and disease and discovering new, patient-specific therapeutics. When combined with advances in minimally-invasive cardiac delivery, ongoing efforts will likely lead to scalable cell and biomaterial technologies for use in clinical practice. In this review, we describe recent progress in the field of cardiac tissue engineering with particular emphasis on use of biomaterials for therapeutic tissue design and delivery.

Keywords: Biomaterials; Bioprinting; Cardiac tissue engineering; Hydrogel; Nanomaterials.

Figure 1.. Cell sources and architectures for engineered cardiac tissues

A) Cardiomyocytes for engineering of fECTs can be differentiated from human pluripotent stem cells or isolated from neonatal rodent ventricles; B) A variety of fECT architectures have been developed, including cell sheets, spheroids, bundles, patches, and single ventricle analogs.

Figure 2.. Materials and techniques for engineering cardiac tissues

Materials and techniques most frequently used for fECT engineering and therapy include: A) hydrogel scaffolds made from either natural or synthetic materials formed with 3D molding or bioprinting; B) fibrous scaffolds generated from synthetic materials including PLGA, PGS and others; C) nanofibrous scaffolds generated through electrospinning or extrusion spinning; D) decellularized tissues either intact or homogenized and crosslinked into a hydrogel; and E) injectable scaffolds to provide bulking and/or beneficial remodeling of the treated heart.