Mimicking cardiac tissue complexity through physical cues: A review on cardiac tissue engineering approaches

Cardiovascular diseases are the number one killer in the world.(1,,2) Currently. there are no clinical treatments to regenerate damaged cardiac tissue, leaving patients to develop further life-threatening cardiac complications. Cardiac tissue has multiple functional demands including vascularization, contraction. and conduction that require many synergic components to properly work. Most of these functions are a direct result of the cardiac tissue structure and composition, and, for this reason, tissue engineering strongly proposed to develop substitute engineered heart tissues (EHTs). EHTs usually have combined pluripotent stem cells and supporting scaffolds with the final aim to repair or replace the damaged native tissue. However, as simple as this idea is, indeed, it resulted, after many attempts in the field, to be very challenging. Without design complexity, EHTs remain unable to mature fully and integrate into surrounding heart tissue resulting in minimal in vivo effects.(,3) Lately. there has been a growing body of evidence that a complex, multifunctional approach through implementing scaffold designs, cellularization, and molecular release appears to be essential in the development of a functional cardiac EHTs.(4-6) This review covers the advancements in EHTs developments focusing on how to integrate contraction, conduction, and vascularization mimics and how combinations have resulted in improved designs thus warranting further investigation to develop a clinically applicable treatment. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

Cardiovascular diseases are the leading cause of death globally, and there are currently no clinical treatments available to regenerate damaged cardiac tissue. Tissue engineering aims to develop engineered heart tissues (EHTs) as substitutes, but the challenge lies in achieving full maturity and integration into the surrounding heart tissue for effective treatment. Recent advancements suggest that a multifunctional approach involving scaffold designs, cellularization, and molecular release is crucial for developing functional cardiac EHTs.