Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs

Abstract

Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications.

Personalized Hydrogels for Engineering Diverse Fully Autologous Tissue Implants

“…[41] Endothelial cell (EC) differentiation is essential for vascularization, which improves the probability of efficient engraftment following transplantation. [42] Therefore, we next evaluated the potential of the hydrogel to support EC differentiation. iPSCs were subjected to an EC differentiation protocol for seven days, and CD31 expression was then assessed (Figure 3g).…”

“…Endothelial cell (EC) differentiation is essential for vascularization, which improves the probability of efficient engraftment following transplantation . Therefore, we next evaluated the potential of the hydrogel to support EC differentiation.…”

Aspects of Lyophilization of Cardiac Bioimplant

“…Also, grafts that are to a certain extent populated with cells and delivered to the site of injury can help restore lost heart cells and further recovery. An ideal scaffold should be compatible with all types of heart cells, provide mechanical strength in the right place, properly order cells and transmit biochemical signals for the proper functioning of cells in the heart [4]. Sources of such scaffolds can be biological or synthetic materials, each of which has its own advantages and disadvantages.…”

Guest Editorial: Vascularization in Tissue Engineering

“…[20][21][22] The three reviews in this series cover cardiovascular repair strategies in varying depths, provide insights into the status of the field, and explore some of the future directions for engineered tissues as well as for therapies focused on correcting the underlying microvascular dysfunction. Wang et al 23 provide a concise review of the efforts in improving perfusion using cells and growth factors, the use of natural and synthetic scaffolds, including decellularized myocardium, and the use of complex bioreactors, for cardiac tissue engineering (Issues 5-6, Page 455). An engaging and timely commentary on the need for uniform standards in tissue-engineered therapeutics is also provided.…”