Abstract

Cardiovascular disease is one of the leading causes of mortality worldwide. Cardiac tissue engineering strategies focusing on biomaterial scaffolds incorporating cells and growth factors are emerging as highly promising for cardiac repair and regeneration. The use of stem cells within cardiac microengineered tissue constructs present an inherent ability to differentiate into cell types of the human heart. Stem cells derived from various tissues including bone marrow, dental pulp, adipose tissue and umbilical cord can be used for this purpose. Approaches ranging from stem cell injections, stem cell spheroids, cell encapsulation in a suitable hydrogel, use of prefabricated scaffold and bioprinting technology are at the forefront in the field of cardiac tissue engineering. The stem cell microenvironment plays a key role in the maintenance of stemness and/or differentiation into cardiac specific lineages. This review provides a detailed overview of the recent advances in microengineering of autologous stem cell-based tissue engineering platforms for the repair of damaged cardiac tissue. A particular emphasis is given to the roles played by the extracellular matrix (ECM) in regulating the physiological response of stem cells within cardiac tissue engineering platforms.

Highlights

  • Cardiovascular disease (CVD) is the leading cause of mortality worldwide accounting for over 30% of deaths [1]

  • We focus on the importance and mechanisms of microenvironmental factors for the maintenance and differentiation of stem cells, as well as challenges and future trends of stem cell-based cardiac microengineered tissues for a number of clinical applications

  • Stem cells are sensitive to nanotopographical cues and tend to undergo differentiation on this patterned surface. This suggests that coexisting biophysical signals as part of the synthetic microenvironment play an important role for stem cells differentiation [60]

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Summary

Introduction

Cardiovascular disease (CVD) is the leading cause of mortality worldwide accounting for over 30% of deaths [1]. Over the past several decades, life-saving organ transplantations and the use of biomaterial-based implants have been employed extensively in people with organ damage or failure [4] Such interventions are associated with limitations including the lack of available or suitable organs and the need for continuous use of immunosuppressive drugs post organ transplantation, often associ­ ated with severe side effects [5]. Autologous stem cells have a number of advantages over allogeneic stem cells including immuno­ compatibility [26] Another approach to generate autologous stem cells is to isolate differentiated adult cells, e.g. skin fibroblasts, and treat these ex vivo with stem cell transcription factors to produce iPSCs [27]. We focus on the importance and mechanisms of microenvironmental factors for the maintenance and differentiation of stem cells, as well as challenges and future trends of stem cell-based cardiac microengineered tissues for a number of clinical applications

The importance of stem cells microenvironment in tissue engineering
Engineering an appropriate ECM microenvironment
Textural and topographic microenvironment considerations
Biological mechanisms important for stem cell function within tissues
The importance of the stem cells origin in tissue engineering
Chemically-induced stem cell differentiation
The influence of electrical microenvironment on stem cell differentiation
Cardiac tissue engineering and clinical potential
Utilizing stem cells in cardiac tissue engineering
Injecting stem cells directly into damaged myocardium
Spheroids in cardiac repair
Cardiac repair patches
Tissue engineered heart valves
Bioprinting of myocardial tissues for transplantation
Challenges and prospects in cardiac tissue engineering
Findings
Conclusions
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