Researchers have succeeded in growing heart muscle tissue on a substrate made from 3D-printed, bioengineered spider silk. The results show promise for the production of functional heart tissue for improving cardiac function after heart attacks and strokes.
Cardiovascular disease is a major health problem around the world, causing high morbidity and mortality and driving up the cost of health care. An increasing number of people are suffering from cardiac problems, despite significant advances in preventing and minimizing heart disease. Reduced cardiac functionality is largely the result of irreversible loss of cardiac muscle cells due to events such as heart attack and stroke. At present there is still no treatment for reversing this kind of heart damage.
The primary cause of impaired heart function is loss of cardiomyocytes (heart muscle cells). Cardiac tissue engineering has the potential to restore this damaged myocardial tissue. One innovative approach that is being studied is using spider silk to help grow new cardiac muscle tissue.
Spider silk has been the focus of some interesting research in recent years. For example, Felix Engel, professor for experimental renal and cardiovascular research at Friedrich-Alexander-University Erlangen-Nuremberg, has studied the properties of silk from the Indian silkworm and has shown its suitability as scaffolding material for engineering cardiac tissue. A limitation, however, is that spider silk protein is difficult to produce in sufficient quantities and at a consistent quality.
In 2015, a research team led by Thomas Scheibel, professor of biomaterials at University of Bayreuth, was successful in mixing spider silk with fibroblast cells from mice to generate a so-called "bio ink" or gel using 3D printing. The gel flowed through the print head onto an extrusion surface, changing rapidly from a fluid to a firm state. The silk molecules enveloped the rat cells, providing a porous matrix for growth.
These experts shared their expertise to successfully develop heart muscle tissue based on spider silk scaffolds and cardiomyocytes. The results, which showed that bioengineered spider silk hydrogels can be an effective base for the restoration of heart tissue, was recently published in Advanced Functional Materials.
Approach and Methodology
Spider silk is an excellent material to produce hydrogels, from which tissue-like structures can be produced via 3D-printing. Living cells that are incorporated into such hydrogels remain stable and functional. The researchers were especially interested in the proteins in the silk that provide structure and mechanical stability.
The team used a bioengineered spider silk protein called eADF4(κ16). The protein was applied as a thin film on a glass substrate. Cells with a negatively charged surface adhere to films made of eADF4(κ16) because of the protein’s positive charge. Several different primary rat heart cells were then placed on the film. The cardiomyocytes, fibroblasts, endothelial cells, and smooth muscle cells attached well to the eADF4(κ16) films on the glass coverslips, which provided an engineered surface with a polycationic character. The researchers discovered that the factors leading to hypertrophy (the growth of muscle cells) also led to an increased volume growth in the heart muscle cells that grew on the eADF4(κ16) layer. Also, cardiomyocytes grown on eADF4(κ16) films responded to pro-proliferative factors and exhibited proper cell-to-cell communication and electric coupling.
These promising results show that patients suffering from cardiac infarction might have a real chance in the future to restore their damaged heart tissue, thanks to spider silk and 3D-printing.
Collectively, the data demonstrate that designed recombinant eADF4(κ16)-based materials are promising materials for cardiac tissue engineering. Some companies have started to commercialize spider-silk-based biomaterials. For example, Spiber Technologies AB, a Swedish biomaterials company, is using genetically engineered bacteria and a protein purification technology to produce large quantities of spider-silk proteins that can customized for a variety of specific purposes. Spider silk protein is now available as fiber, film, foam, and even mesh. The material remains stable at boiling temperatures of up to 267 degrees Celsius (512 Fahrenheit). The company is working to develop spider silk applications across several medical fields, including cardiology, heart tissue regeneration, bone reconstruction, skin cell growth, and vaccines.
Engel and Scheibel are excited about the potential of using 3D printing and spider silk to produce functional heart tissue. “Functional heart tissue could get produced in the lab soon,” states Scheibel. “The only question is when and how these results can get used in the clinics.”
Mark Crawford is a technical writer based in Madison, WI.
Read more about tissue engineering on AABME.org.