Abstract

Since the term “smart materials” was put forward in the 1980s, stimuli-responsive biomaterials have been used as powerful tools in tissue engineering, mechanobiology, and clinical applications. For the purpose of myocardial repair and regeneration, stimuli-responsive biomaterials are employed to fabricate hydrogels and nanoparticles for targeted delivery of therapeutic drugs and cells, which have been proved to alleviate disease progression and enhance tissue regeneration. By reproducing the sophisticated and dynamic microenvironment of the native heart, stimuli-responsive biomaterials have also been used to engineer dynamic culture systems to understand how cardiac cells and tissues respond to progressive changes in extracellular microenvironments, enabling the investigation of dynamic cell mechanobiology. Here, we provide an overview of stimuli-responsive biomaterials used in cardiovascular research applications, with a specific focus on cardiac tissue engineering and dynamic cell mechanobiology. We also discuss how these smart materials can be utilized to mimic the dynamic microenvironment during heart development, which might provide an opportunity to reveal the fundamental mechanisms of cardiomyogenesis and cardiac maturation.

Highlights

  • Human myocardium is constantly regulated by dynamic external microenvironmental cues, including biochemical, mechanical, and electrical signals

  • We discuss how these smart materials can be utilized to mimic the dynamic microenvironment during heart development, which might provide an opportunity to reveal the fundamental mechanisms of cardiomyogenesis and cardiac maturation

  • The advancement of stimuli-responsive biomaterials has great potential to make a profound contribution to the field of cardiac mechanobiology, which can guide the future design for cardiac tissue regeneration applications

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Summary

INTRODUCTION

Human myocardium is constantly regulated by dynamic external microenvironmental cues, including biochemical, mechanical, and electrical signals. These signals propagate through cell–cell or cell–extracellular matrix (ECM) interfaces and act on intracellular signaling pathways. With the incorporation of azobenzene, the elasticity of poly(ethylene glycol) (PEG) hydrogel could be reversibly modulated by switching the light exposure between visible and ultraviolet (UV) light and could be used to provide dynamic biophysical controls to the encapsulated cells.[26] Using nucleic acid sequences as crosslinkers, biopolymers were fabricated with tunable properties that could be controlled based on the complementary hybridization of different nucleotides. We highlight the recent development of stimuli-responsive biomaterials for creating dynamic cell microenvironments for cardiac mechanobiological studies (Fig. 1)

STIMULI-RESPONSIVE BIOMATERIALS IN CARDIAC TISSUE REGENERATION
Smart hydrogels for cell transplantation
Smart hydrogels for drug delivery
Nanoparticles and nanogels
STIMULI-RESPONSIVE BIOMATERIALS IN DYNAMIC CARDIAC MECHANOBIOLOGY
Stimuli in cardiac mechanobiology
Dynamic cell mechanobiology
Dynamic substrate topography on cardiac mechanobiology
Effect of dynamic substrate stiffness on cardiac mechanobiology
CONCLUSION AND FUTURE PERSPECTIVE
Methods
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