Applications of Tissue Decellularization Techniques in Ventricular Myocardial Biofabrication.

Aravind Krishnan,John Ward Macarthur,Hanjay Wang

doi:10.3389/fbioe.2022.802283

Aravind Krishnan, John Ward Macarthur + Show 1 more

Open Access

https://doi.org/10.3389/fbioe.2022.802283

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Abstract

Ischemic heart disease is the leading cause of death around the world, and though the advent of coronary revascularization has revolutionized its treatment, many patients who sustain ischemic injury to the heart will go on to develop heart failure. Biofabrication of ventricular myocardium for replacement of irreversibly damaged ischemic myocardium is sought after as a potential therapy for ischemic heart failure, though challenges in reliably producing this biomaterial have limited its clinical application. One method that shows promise for generation of functional myocardium is the use of tissue decellularization to serve as a scaffold for biofabrication. This review outlines the methods, materials, challenges, and prospects of tissue decellularization techniques for ventricular myocardium biofabrication. Decellularization aims to preserve the architecture and composition of the extracellular matrix of the tissue it is applied to, allowing for the subsequent implantation of stem cells of the desired cell type. Decellularization can be achieved with multiple reagents, most of which have detergent properties. A variety of cell types can be implanted in the resulting scaffold, including cardiac progenitor cells, and embryonic or induced pluripotent stem cells to generate a range of tissue, from patches to beating myocardium. The future of this biofabrication method will likely emphasize patient specific tissue engineering to generate complex 3-dimensional constructs that can replace dysfunctional cardiac structures.

Highlights

Ischemic heart disease remains the number one cause of mortality around the world (Virani et al, 2021)
The “bottom-up” approach focuses on bioprinting scaffolds from native or engineered extracellular matrix components with or without colocalized progenitor cell lines that differentiate into myocardium (Ong et al, 2018)
Chemical decellularization is most commonly achieved with a detergent agent such as sodium dodecyl sulfate (SDS), which can be used in conjunction with other detergents such as Triton X-100 in optimal concentrations to preserve the architecture of the extracellular matrix (Ott et al, 2008; Cebotari et al, 2010; Keane et al, 2015; Gilpin and Yang, 2017)

Summary

INTRODUCTION

Ischemic heart disease remains the number one cause of mortality around the world (Virani et al, 2021). Li et al addressed this challenge by decellularizing adult rat hearts to produce dECM patches, and subsequently recellularizing them with iPSCs genomically engineered through transcription activator-like effector nucleases (TALEN) to select for cues to differentiate into ventricular cardiomyocytes (Garreta et al, 2016; Li et al, 2017) The result of this decellularization-recellularization method was functional, electrically conductive, beating ventricular myocardium in a petri dish (Li et al, 2017). Prior work has utilized fibrin scaffolds instead of decellularized umbilical cord as the conduit, producing a much smaller amount of stroke work compared to the method developed by Kubo et al (2007); Park et al (2020)

Limitations and Future

Findings

CONCLUSION