Researchers at the Georgia Institute of Technology have designed a new scaffold for tissue engineering by crocheting yarns into a fabric, a method that shows the potential to imitate properties of human skin — or even organs — that are difficult to replicate in a laboratory.
Though human tissues are notoriously hard to mimic, they're sorely needed, the authors explained in the study, published April 8 in Journal of the Mechanical Behavior of Biomedical Materials.
"The supply chain for organ transplant will never be sustainable without engineered tissues," Kan Wang, the study's corresponding author and a research engineer at Georgia Tech, told The Academic Times. As of February 2021, more than 107,000 adults and children in the U.S. were still waiting for an organ transplant. 17 of them die with each passing day. Meanwhile, the waiting list continues to grow at a fast rate — one person is added every nine minutes. Wang and his team of tissue engineers hope to close this gap by creating non-living substitutes that are biologically similar to human tissue.
Growing artificial or living muscle on scaffolds is not a new idea: Cell-based meat companies such as Mosa Meat and GOOD Meat have years of experience cultivating animal tissues in a laboratory setting. However, as the authors of this study reported, "mimicking the strain-stiffening property of human tissues by using synthetic materials is still a challenge."
Most synthetic materials show strain-softening behavior, which is the opposite of what materials scientists want. At the atomic level, chains of molecules will either stiffen or harden under different conditions which are often hard to control — and the material itself also matters. "Synthetic polymers tend to have mechanical behaviors different from biological tissues," Wang explained.
Materials that exhibit strain-hardening behavior are ideal for tissue engineering because they can serve as a scaffold. Tissues including muscle cannot be formed on their own; a hard base is required to give the tissue a structure similar to that inside the human body. "I realized that some researchers are trying to recreate a dynamic microenvironment when growing tissues," said Wang. He saw an opportunity to apply his past research on fiber structures in the human heart.
In recent years, Wang focused on manufacturing technology that could be applied to biomedical research. He was part of a collaborative project with heart surgeons at the Piedmont Atlanta Hospital in Georgia that yielded individual models of patients' heart valves. The team combined computed tomography, a more in-depth variation on standard X-ray imaging, with 3D printing to engineer these personalized models that the doctors could test before performing surgery on a patient. "One takeaway I got from that project is that fibrous structures can mimic biological tissues," Wang noted. "It occurred to me that fibrous scaffolds may have some advantages in … growing tissues outside of the human body."
In the current study, Wang and his colleagues engineered a sandwich-like scaffold to imitate the strain stiffening of human tissues. They used a process called electrospinning that creates yarns woven into patterns such as scaffolds. The novel scaffold in this study is made up of multiple layers, placed on top of one another to form a kind of molecular sandwich. "The sandwich scaffold has similar organizations to human skin ... with a thick outer layer," the authors noted in the study.
The wet electrospinning process used by Wang and his team changes the fibers on a cellular level, opening "a window to tweak the properties of the yarn," Wang said. A liquid chemical bath transfers molecules onto scaffolds in a way that prompts cells to align and elongate — two phenomena that are key to inducing strain-stiffening behavior. The resulting scaffold has higher maximum stress and maximum strain after wet electrospinning, making it more similar to human skin. It is also more versatile in the types of tissues it can support, which include human skin, muscle and connective fibers.
"Our next step is to explore more functions we can introduce to the scaffold by adding materials to the yarn," Wang said. One material that has already proved promising: carbon nanotubes. These minuscule hollow tubes are built from carbon atoms. In a preliminary test, they were shown to improve the alignment and elongation of the tissue cells even beyond the improvements realized through the current process. The team also plans to test graphene and boron nitride nanotubes, a material that has previously been used to repair human bones, and intends to look into different weaving patterns for the scaffolds themselves.
"This study validates the potential of the sandwich scaffold to mimic the physical, mechanical, and biological properties of human skin and other tissues," the authors noted in the study. Wang thinks the scaffolds can be easily scaled up in the near future. "Scaling up could bring down the cost of engineered tissues, which means they are more likely to be covered by health insurance," he added.
Replacing diseased or damaged organs, such as a sick liver with an artificial one, is another crucial application of this technology. "If the affordability and accessibility of these technologies can be improved, many lives could be saved … and quality of life could significantly increase," Wang noted.
"I believe all researchers in this field wish that engineered tissues are more accessible to patients," he added.
The study, "Textile-based sandwich scaffold using wet electrospun yarns for skin tissue engineering," published April 8 in Journal of the Mechanical Behavior of Biomedical Materials, was authored by Chen Jiang, Kan Wang, Yi Liu, Chuck Zhang and Ben Wang, Georgia Institute of Technology.