Natural Biomaterials for Cardiac Tissue Engineering: A Highly Biocompatible Solution.

Qasim A Majid,Sian E Harding,Serena Best,Annabelle T R Fricker,Ruth Cameron,Pooja Basnett,Thomas J Owen,Richard J Jabbour,Barbara Lukasiewicz,Sanjay Sinha,Ipsita Roy,Olivia Hernandez Cruz,David A Gregory,Natalia Davidenko,Molly Stevens

doi:10.3389/fcvm.2020.554597

Abstract

Cardiovascular diseases (CVD) constitute a major fraction of the current major global diseases and lead to about 30% of the deaths, i.e., 17.9 million deaths per year. CVD include coronary artery disease (CAD), myocardial infarction (MI), arrhythmias, heart failure, heart valve diseases, congenital heart disease, and cardiomyopathy. Cardiac Tissue Engineering (CTE) aims to address these conditions, the overall goal being the efficient regeneration of diseased cardiac tissue using an ideal combination of biomaterials and cells. Various cells have thus far been utilized in pre-clinical studies for CTE. These include adult stem cell populations (mesenchymal stem cells) and pluripotent stem cells (including autologous human induced pluripotent stem cells or allogenic human embryonic stem cells) with the latter undergoing differentiation to form functional cardiac cells. The ideal biomaterial for cardiac tissue engineering needs to have suitable material properties with the ability to support efficient attachment, growth, and differentiation of the cardiac cells, leading to the formation of functional cardiac tissue. In this review, we have focused on the use of biomaterials of natural origin for CTE. Natural biomaterials are generally known to be highly biocompatible and in addition are sustainable in nature. We have focused on those that have been widely explored in CTE and describe the original work and the current state of art. These include fibrinogen (in the context of Engineered Heart Tissue, EHT), collagen, alginate, silk, and Polyhydroxyalkanoates (PHAs). Amongst these, fibrinogen, collagen, alginate, and silk are isolated from natural sources whereas PHAs are produced via bacterial fermentation. Overall, these biomaterials have proven to be highly promising, displaying robust biocompatibility and, when combined with cells, an ability to enhance post-MI cardiac function in pre-clinical models. As such, CTE has great potential for future clinical solutions and hence can lead to a considerable reduction in mortality rates due to CVD.

Highlights

Specialty section: This article was submitted to Cardiovascular Biologics and Regenerative Medicine, a section of the journal Frontiers in Cardiovascular Medicine
The general strategy for cardiac tissue engineering is to combine functional cardiomyocytes and biomaterials with carefully designated characteristics to repair and restore diseased heart tissue [2,3,4,5]. The selection of these biomaterials is a challenging task due to the strict requirements imposed on the heart TE substrates [2, 3, 6], which are required to support cell attachment and alignment, and to transmit load, provide physiologically relevant stiffness, and be degraded and replaced over time by extracellular matrix (ECM) proteins secreted by cells
A family of naturally occurring biomaterials produced via bacterial fermentation, are explored with particular attention paid to the use of the latter for left ventricular cardiac patches and cardiac valve replacement

Summary

Introduction

Specialty section: This article was submitted to Cardiovascular Biologics and Regenerative Medicine, a section of the journal Frontiers in Cardiovascular Medicine. Fibrinogen, collagen, alginate, and silk are isolated from natural sources whereas PHAs are produced via bacterial fermentation Overall, these biomaterials have proven to be highly promising, displaying robust biocompatibility and, when combined with cells, an ability to enhance post-MI cardiac function in pre-clinical models. The development of Engineered Heart Tissue (EHT) was pioneered by Thomas Eschenhagen [7] and was created by combining cardiomyocytes and or non-cardiomyocytes within an ECM to form a 3D construct Such ECM-like gel-based cardiac patches possess the advantage of being shaped or cast to the complex geometry of the myocardium, so providing efficient bonding to the native tissue. EHTs are being used as tools for drug screening, disease modeling, and in cardiac regeneration to replace lost myocytes post-myocardial infarction, and are on the cusp of being approved for clinical trials [9]

Objectives

Findings

Conclusion