Engineering Functional Cardiac Tissues for Regenerative Medicine Applications

Abstract

Purpose of Review Tissue engineering has expanded into a highly versatile manufacturing landscape that holds great promise for advancing cardiovascular regenerative medicine. In this review, we provide a summary of the current state-of-the-art bioengineering technologies used to create functional cardiac tissues for a variety of applications in vitro and in vivo. Recent Findings Studies over the past few years have made a strong case that tissue engineering is one of the major driving forces behind the accelerating fields of patient-specific regenerative medicine, precision medicine, compound screening, and disease modeling. To date, a variety of approaches have been used to bioengineer functional cardiac constructs, including biomaterialbased, cell-based, and hybrid (using cells and biomaterials) approaches. While some major progress has been made using cellular approaches, with multiple ongoing clinical trials, cell-free cardiac tissue engineering approaches have also accomplished multiple breakthroughs, although drawbacks remain. Summary This review summarizes the most promising methods that have been employed to generate cardiovascular tissue constructs for basic science or clinical applications. Further, we outline the strengths and challenges that are inherent to this field as a whole and for each highlighted technology.

Engineering Human Cardiac Muscle Patch Constructs for Prevention of Post-infarction LV Remodeling

“…These trials demonstrated feasibility and safety of clinical translation of hESC-derived cardiovascular progenitors, paving the way for further efforts of efficacy studies. Recently, CPCs have shown promise as a highly reproductive cell source in additive cardiac tissue manufacturing, as an alternative to the non-proliferative, mature CMs, to create highly cellularized function hCMPs (92)(93)(94).…”

“…Conventional methods for manufacturing hCMPs include generating contiguous sheets of cardiac cells (mainly CMs) or suspending cells of a variety of types in scaffolds of biocompatible material (94,(105)(106)(107)(108). More recently, the emergence of 3D printing technologies, combined with cell-containing "bioinks" and computer-aided design (CAD), has enabled researchers to define the architecture of hCMPs with previously unattainable precision (Figure 3).…”

When Stiffness Matters: Mechanosensing in Heart Development and Disease

“…However, as mentioned previously, the canonical 2D culture and differentiation of these cells still has major limitations, most notably their immature phenotype, which lacks to fully represent developed tissue. The development of new biomaterials (Reis et al, 2016;Wissing et al, 2017;Kuraitis et al, 2019) and the emerging of new technologies such as tissue printing (Charbe et al, 2019;Tomov et al, 2019), organ on a chip (Marsano et al, 2016;Ugolini et al, 2018;Wan et al, 2018), and different types of bioreactors that allow mechanical, perfusion, or electrical stimulation (Freed et al, 2006;Lei and Ferdous, 2016;Paez-Mayorga et al, 2019) allow us to generate cardiac tissue that more closely recapitulate the (patho)physiological features of the developed myocardium. Moreover, these models represent an optimal tool not only to test and validate new drugs or to re-create tissue substitute for regenerative medicine application but also to allow a better understanding of the molecular mechanisms behind disease development and progression.…”

Advances in tissue engineering of the cardiac muscle for myocardial regeneration

“…A biomimetic biomaterial can be any scaffolding material that mimics the characteristics of the natural ECM. They are based on polymers that may be natural, synthetic or biosynthetic (26,28). They are interesting for the repair and regeneration of tissues due to their biodegradability, mechanical properties or high porosity.…”