How to Fix a Broken Heart
By Emily Yang
You’re probably familiar with the Hollywood representation of heart trauma—the clutching of the chest, the tingling pain radiating down the left arm, the shortness of breath. These symptoms are classic signs of a myocardial infarction, commonly known as a heart attack.
Myocardial infarction (MI) begins when fats deposit along the walls of coronary arteries, the blood vessels that carry oxygenated blood to the heart. These fats harden and form plaques that can significantly block blood flow, preventing oxygen delivery to the heart’s muscle cells. Infarction occurs when these cells die due to inadequate oxygen supply, and up to 50% of the cardiac muscle cells can be lost permanently [1]. MI remains one of the deadliest ailments in the world, representing over 26% of all global deaths [2]. Because cardiac muscle cells can’t regenerate, mechanically and electrically inactive scar tissue is formed instead, which is why most MI survivors subsequently develop heart failure.
Current treatments for MI can only prevent further cellular damage rather than repair it, with heart transplantation as the only available option for replacing the damaged cells. However, because of the extremely limited organ donor pool, research into alternative therapies utilizing cell and tissue engineering has rapidly expanded. For decades, researchers experimented with cardiomyoplasty—a technique in which muscle tissue from other body parts is wrapped around the heart. However, clinical trials for this technique were met with little success, resulting in low cell survival rate and the development of abnormal cardiac rhythms. Researchers have also experimented with injecting damaged heart tissue with stem cells, cells that can develop into a variety of cell types. Although this has shown some clinical success, the technique is inefficient in that it kills many of the cells due to the physical stress of the injection process [3].
One of the more promising therapies on the rise is cardiac patches. Like heat rubs or nicotine patches that you can buy at your local pharmacy, cardiac patches work via a similar concept—a patch that can be stuck onto tissue, revitalizing its surroundings. Cardiac patches are sheets of cells grown onto a scaffold, which is a 3D template that determines the cellular arrangement and enables the cells to proliferate. The scaffold is typically made of fibrin and collagen, proteins naturally found in the body that are used for external structural support. The cardiac muscle cells are typically derived from induced-pluripotent stem cells, a type of stem cell that is created from mature adult cells. The scaffold encourages cell growth by releasing regenerative growth factors, such as vitamins and hormones, that are needed to continuously stimulate development. Like a physical brace, the scaffold’s presence is temporary and is naturally degraded by the body within a span of days [3].
Development of the cardiac patch has rapidly progressed over the past few years, with new variations in structure, cell composition, and multi-tissue interactions. Studies have continued to show success in the patches’ ability to restore cardiac function. However, this technology’s potential is limited by the relatively primitive surgical techniques needed for its application. As of now, administering cardiac patches would require open-heart surgery, an intensive procedure in which the chest and breast bone must be cut open to expose the heart, and these rather extreme methods have kept the technology confined to the lab bench.
To address such drawbacks, a group of researchers led by Dr. Junnan Tang of Zhengzhou University have created a minimally-invasive application method, inspired by the technique conventionally reserved for industrial workers and street artists—spray painting [4].
Tang’s team hypothesized that polymerizable biomaterials—polymers that can be used inside the body—could be spray painted onto the heart to form a cardiac patch. To test their theory, they used a mouse model and platelet fibrin gel, a biomaterial commonly used in animal studies for cardiac repair, as their “paint”. To create the “spray”, a syringe filled with the gel was connected to a tube that delivered pressurized CO2 to the syringe tip (Figure 1).
To see whether spraying affected the gel’s properties, the researchers ran a variety of tests to assess its characteristics, discovering that the material could still form a stable patch with the desired fibrous structure. The gel could also release the needed growth factors, remained nontoxic to the cells, and kept cell function intact.
Moving on to the mouse model studies, groups of mice were induced with MIs and the damaged tissue was treated with the sprayed cardiac patch. Rather than performing open-heart surgery, the hearts were exposed through a left thoracotomy, a minimally invasive procedure that opens the chest wall. Of the MI-induced mice, the survival rate of the treated mice was around 18% higher than that of the untreated mice The treated mice also had less abnormal tissue structure, decreased tissue death, and more cells that had maintained their shape and size. The researchers also found that the spray treatment could potentially both preserve cell function and block apoptosis, a programmed form of cell death. Furthermore, unlike the previous cardiac patches, the spray treatment improved cardiac function without having to pre-grow cells onto the patch [4].
These discoveries have not only confirmed the effectiveness of cardiac patch technology, but have also shown that minimally invasive procedures are possible, redefining the boundaries of MI treatments. Spray-painting biomaterials is not solely limited to the heart, as scaffolds are a major component of all forms of tissue engineering. Treating the untreatable no longer seems so distant—one could say that it’s now a matter of the heart.
References
You’re probably familiar with the Hollywood representation of heart trauma—the clutching of the chest, the tingling pain radiating down the left arm, the shortness of breath. These symptoms are classic signs of a myocardial infarction, commonly known as a heart attack.
Myocardial infarction (MI) begins when fats deposit along the walls of coronary arteries, the blood vessels that carry oxygenated blood to the heart. These fats harden and form plaques that can significantly block blood flow, preventing oxygen delivery to the heart’s muscle cells. Infarction occurs when these cells die due to inadequate oxygen supply, and up to 50% of the cardiac muscle cells can be lost permanently [1]. MI remains one of the deadliest ailments in the world, representing over 26% of all global deaths [2]. Because cardiac muscle cells can’t regenerate, mechanically and electrically inactive scar tissue is formed instead, which is why most MI survivors subsequently develop heart failure.
Current treatments for MI can only prevent further cellular damage rather than repair it, with heart transplantation as the only available option for replacing the damaged cells. However, because of the extremely limited organ donor pool, research into alternative therapies utilizing cell and tissue engineering has rapidly expanded. For decades, researchers experimented with cardiomyoplasty—a technique in which muscle tissue from other body parts is wrapped around the heart. However, clinical trials for this technique were met with little success, resulting in low cell survival rate and the development of abnormal cardiac rhythms. Researchers have also experimented with injecting damaged heart tissue with stem cells, cells that can develop into a variety of cell types. Although this has shown some clinical success, the technique is inefficient in that it kills many of the cells due to the physical stress of the injection process [3].
One of the more promising therapies on the rise is cardiac patches. Like heat rubs or nicotine patches that you can buy at your local pharmacy, cardiac patches work via a similar concept—a patch that can be stuck onto tissue, revitalizing its surroundings. Cardiac patches are sheets of cells grown onto a scaffold, which is a 3D template that determines the cellular arrangement and enables the cells to proliferate. The scaffold is typically made of fibrin and collagen, proteins naturally found in the body that are used for external structural support. The cardiac muscle cells are typically derived from induced-pluripotent stem cells, a type of stem cell that is created from mature adult cells. The scaffold encourages cell growth by releasing regenerative growth factors, such as vitamins and hormones, that are needed to continuously stimulate development. Like a physical brace, the scaffold’s presence is temporary and is naturally degraded by the body within a span of days [3].
Development of the cardiac patch has rapidly progressed over the past few years, with new variations in structure, cell composition, and multi-tissue interactions. Studies have continued to show success in the patches’ ability to restore cardiac function. However, this technology’s potential is limited by the relatively primitive surgical techniques needed for its application. As of now, administering cardiac patches would require open-heart surgery, an intensive procedure in which the chest and breast bone must be cut open to expose the heart, and these rather extreme methods have kept the technology confined to the lab bench.
To address such drawbacks, a group of researchers led by Dr. Junnan Tang of Zhengzhou University have created a minimally-invasive application method, inspired by the technique conventionally reserved for industrial workers and street artists—spray painting [4].
Tang’s team hypothesized that polymerizable biomaterials—polymers that can be used inside the body—could be spray painted onto the heart to form a cardiac patch. To test their theory, they used a mouse model and platelet fibrin gel, a biomaterial commonly used in animal studies for cardiac repair, as their “paint”. To create the “spray”, a syringe filled with the gel was connected to a tube that delivered pressurized CO2 to the syringe tip (Figure 1).
To see whether spraying affected the gel’s properties, the researchers ran a variety of tests to assess its characteristics, discovering that the material could still form a stable patch with the desired fibrous structure. The gel could also release the needed growth factors, remained nontoxic to the cells, and kept cell function intact.
Moving on to the mouse model studies, groups of mice were induced with MIs and the damaged tissue was treated with the sprayed cardiac patch. Rather than performing open-heart surgery, the hearts were exposed through a left thoracotomy, a minimally invasive procedure that opens the chest wall. Of the MI-induced mice, the survival rate of the treated mice was around 18% higher than that of the untreated mice The treated mice also had less abnormal tissue structure, decreased tissue death, and more cells that had maintained their shape and size. The researchers also found that the spray treatment could potentially both preserve cell function and block apoptosis, a programmed form of cell death. Furthermore, unlike the previous cardiac patches, the spray treatment improved cardiac function without having to pre-grow cells onto the patch [4].
These discoveries have not only confirmed the effectiveness of cardiac patch technology, but have also shown that minimally invasive procedures are possible, redefining the boundaries of MI treatments. Spray-painting biomaterials is not solely limited to the heart, as scaffolds are a major component of all forms of tissue engineering. Treating the untreatable no longer seems so distant—one could say that it’s now a matter of the heart.
References
- Beans, C. (2018). Inner Workings: The race to patch the human heart. Proceedings of the National Academy of Sciences of the United States of America, 115(26), 6518-6520.
- Li, Dongze, Yu, Jing, Zeng, Rui, Zhao, Lizhi, Wan, Zhi, Zeng, Zhi, & Cao, Yu. (2017). Neutrophil Count Is Associated With Risks of Cardiovascular Diseases. Journal of the American College of Cardiology, 70(7), 911-912.
- Schaefer, J., Guzman, P., Riemenschneider, S., Kamp, T., & Tranquillo, R. (2018). A cardiac patch from aligned microvessel and cardiomyocyte patches. Journal of Tissue Engineering and Regenerative Medicine, 12(2), 546-556.
- Tang, J., et al. (2017). A Regenerative Cardiac Patch Formed by Spray Painting of Biomaterials onto the Heart. Tissue Engineering Part C: Methods, 23(3), 146-155.
Figure 1. Spray painting of biomaterials on heart
Figure 2. SEM image of sprayed platelet fibrin gel
Figure 3. Cardiac patch