Engineering Biomaterials to Guide Heart Cells for Matured Cardiac Tissue

Abstract

The extracellular matrix (ECM) is needed to maintain the structural integrity of tissues and to mediate cellular dynamics. Its main components are fibrous proteins and glycosaminoglycans, which provide a suitable environment for biological functions. Thus, biomaterials with ECM-like properties have been extensively developed by modulating their key components and properties. In the field of cardiac tissue engineering, the use of biomaterials offers several advantages in that biophysical and biochemical cues can be designed to mediate cardiac cells, which is critical for maturation and regeneration. This suggests that understanding biomaterials and their use in vivo and in vitro is beneficial in terms of advancing cardiac engineering. The current review provides an overview of both natural and synthetic biomaterials and their use in cardiac engineering. In addition, we focus on different strategies to recapitulate the cardiac tissue in 2D and 3D approaches, which is an important step for the maturation of cardiac tissues toward regeneration of the adult heart.

Current Advances in 3D Tissue and Organ Reconstruction

“…Many strategies were also developed for 3D heart recreation. Nevertheless, they led to the production of functionally immature contractile cardiac constructs [ 202 , 203 , 204 ]. Furthermore, although cardiomyocytes represent the key cell type of this tissue, the engrafting of stromal and endothelial populations, for the recreation of vascular system, remains the most immediate need for obtaining functional organs [ 198 ].…”

Polymeric Biomaterials for the Treatment of Cardiac Post-Infarction Injuries

“…Thus, scaffold stiffness and geometry are important features to be considered, with square pores being more efficient in promoting cell adhesion rather than hexagonal pores [ 32 ]. Moreover, biochemical cues, such as growth factors [ 33 ], cytokines, and adhesion molecules, should be inserted to induce effective maturation of cardiac cells [ 21 ]. Finally, in order to produce the optimal material for tissue interfaces, the design of the cardiac biomaterial should fit with the complex electrical pathways of the myocardium [ 34 ], obtained by a fine coordination between membrane potential depolarization, pacemaker conduction system, and specific intracellular communication networks [ 35 ].…”

“…Depending on the application area, the properties of the final biomaterials can be tailored by selecting the most appropriate polymer, as well as the synthetic and formulation processes [ 20 ], which are the core expertise of Pharmaceutical Technology. Cardiac scaffolds based on natural or synthetic biomaterial can mimic the ECM environment, with the further possibility to combine the cell therapy with the release of bioactive molecules [ 21 ]. In this regard, different kinds of systems, either in the form of injectable or implanted scaffolds, have been proposed to date [ 22 , 23 ].…”

Recapitulating Cardiac Structure and Function In Vitro from Simple to Complex Engineering

“…For fabricating a heart in vitro, 3D printing technologies will be the baseline technologies. Advances in 3D printing technology made it possible to engineer cardiac tissue from the microscale to the macroscale [ 13 ]. In particular, this technology provides insight for the scaling-up of the constructs including microphysiological devices, patterned tissues, and implantable scaffolds [ 208 , 209 ].…”

“…Although different types of biomaterials, from naturally derived to synthetic ones, have been utilized to mimic in vivo cardiac microenvironment, there are unfulfilled commitments to date. The use of synthetic composites or decellularized ECMs is an attempt to attain the desired ECM materials by providing enhanced structural support and biological signals [ 13 ]. The advancement of ECM materials allows for better cardiac tissue assembly and maturation, and geometrical guidance and force present in the microstructure of the native myocardium are also required.…”