Cardiomyocyte (CM) alignment with striated myofibril organization is developed during early cardiac organogenesis. Previous work has successfully achieved in vitro CM alignment using a variety of biomaterial scaffolds and substrates with static topographic features. However, the cellular processes that occur during the response of CMs to dynamic surface topographic changes, which may provide a model of in vivo developmental progress of CM alignment within embryonic myocardium, remains poorly understood. To gain insights into these cellular processes involved in the response of CMs to dynamic topographic changes, we developed a dynamic topographic substrate that employs a shape memory polymer coated with polyelectrolyte multilayers to produce a flat-to-wrinkle surface transition when triggered by a change in incubation temperature. Using this system, we investigated cellular morphological alignment and intracellular myofibril reorganization in response to the dynamic wrinkle formation. Hence, we identified the progressive cellular processes of human-induced pluripotent stem cell-CMs in a time-dependent manner, which could provide a foundation for a mechanistic model of cardiac myofibril reorganization in response to extracellular microenvironment changes.
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.
Focal adhesion complexes function as the mediators of cell-extracellular matrix interactions to sense and transmit the extracellular signals. Previous studies have demonstrated that cardiomyocyte focal adhesions can be modulated by surface topographic features. However, the response of focal adhesions to dynamic surface topographic changes remains underexplored. To study this dynamic responsiveness of focal adhesions, we utilized a shape memory polymer-based substrate that can produce a flat-to-wrinkle surface transition triggered by an increase of temperature. Using this dynamic culture system, we analyzed three proteins (paxillin, vinculin and zyxin) from different layers of the focal adhesion complex in response to dynamic extracellular topographic change. Hence, we quantified the dynamic profile of cardiomyocyte focal adhesion in a time-dependent manner, which provides new understanding of dynamic cardiac mechanobiology.
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