Nanotechnology in Cardiovascular Regenerative Medicine

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Background

Cardiovascular diseases are the leading causes of morbidity and mortality in the United States and in many other countries around the world. The intrinsic proliferative capacity of cardiomyocytes in the adult mammalian heart is too low to significantly promote structural and functional recovery after injuries. Typically, cardiomyocytes lost after cardiac injury are replaced by fibrotic scar tissue which results in disorders of ventricular function and structure and also leads to progressive heart failure in severe cases. Although heart transplantation is a gold standard for terminal heart failure patients, shortage of donor hearts continues to be a big issue due to the increased demand.

Cardiac tissue engineering provides a promising strategy to guide tissue regeneration and promote functional tissue recovery following cardiac diseases. In this line, many studies have investigated the improvement of local perfusion and vascularization within engineered tissues. Thus, various kinds of three-dimensional (3D) scaffolds are being implanted to lodge functional cells or deliver growth factors and other signaling moieties in animal models and also improve vascularization of the grafted tissues. Utility of biological scaffolds is crucial for promoting vascularization as they mainly provide skeletal support for cell adhesion and are very conducive to lumen formation. In this scenario, as revascularization must occur as soon as possible after flap harvest to keep the tissue alive, rapid vascularization within fabricated biological scaffolds is also crucial, albeit challenging.

Recently, biomaterials technology has evolved in a wide range of applications for creating extracellular matrix (ECM)-mimicking ultrafine fibrous membranes with fiber diameters ranging from nanometers to micrometers. Moreover, their ECM-mimicking structure is conducive to cell adhesion and exchange of substances, which makes these scaffolds intensively studied in promoting vascularization. Therefore, there is an urgent need to fabricate biocompatible biomaterial scaffolds with proper pore size to allow cell migration and mimic native tissue properties. A variety of engineering approaches have been applied to produce ECM-mimicking structures to promote cardiovascular tissue regeneration. Recently, stem cell-derived extracellular vesicles (EVs) have been extensively studied for treating diseases and disorders of many systems, such as the cardiovascular, neurological, musculoskeletal, and immune systems. Multiple advanced engineering approaches have also been applied to develop targeted delivery of EVs for cardiovascular regeneration.

Blood vessel replacement is a common treatment for vascular diseases, such as atherosclerosis, restenosis and aneurysm, with over 500,000 artery bypass procedures performed each year. Vascular autografts represent the current standard of care for vessel replacement, where vessels are retrieved from a patient and transplanted elsewhere in their body. However, as patients have a finite amount of viable vasculature, autografts are characterized by serious donor site morbidity and are severely limited by their availability. Thus, artificial grafts represent a promising alternative to autografts and are frequently employed in the clinics.

Nanotechnology offers promising perspectives in cardiovascular regenerative medicine. Due to their unique properties, nanomaterials provided novel opportunities in cardiovascular tissue engineering. Continued advances of nanomaterial-based tissue engineered technology hold great promise to reduce the demand of donor hearts and blood vessels. Thus far, nanomaterial and nanotechnologies have been extensively tested in various fields of cardiovascular tissue engineering, including drug delivery, engineered cardiac muscle, artificial heart valve, and vascular grafts. Thus, in this Research Topic, we would like to focus on various aspects of nanotechnology relevant to cardiovascular regenerative medicine.

The main theme of this Research Topic is to address current paradigms in nanotechnology-based therapy for myocardial and vascular regeneration, with particular focus on the following topics:

• Nanotechnology with applications in damaged muscle repair and wound healing.
• Nanodevices in diagnosis and screening for early detection of cardiovascular diseases.
• Nanoparticles for cardiovascular imaging and therapeutic delivery (drugs, growth factors, DNA).
• Scaffolds or hydrogels consisting of nanoscale components and exhibiting nanoscale architectures for cell therapy to mimic the native extracellular matrix.
• Extracellular matrix (ECM)-mimicking nanobiomaterials for cardiovascular tissue regeneration.
• Extracellular vesicle (EV)-mimicking nanoparticles for cardiovascular tissue regeneration.
• Vascularized biomaterials using various technologies.
• Drug delivery methods from biomaterials for vascularization.

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Acknowledgement: Jyotsna Joshi helped to write this Research Topic description.

Keywords: Nanotechnology, Heart, Vessel, Injury, Regeneration

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