A team of scientists from the Wake Forest Institute for Regenerative Medicine (WFIRM) in North Carolina has successfully bioprinted a tracheal tissue construct made of multiple materials that fulfill different functions. The printed tissue—the first of its kind—is made up of smooth muscle and cartilage cells which demonstrate similar properties to natural human tracheal tissue.
Up until now, attempts to create artificial tracheal tissue constructs have primarily relied on using regenerated cartilage tissue. By printing the tissue using a biodegradable polyester material and mesenchymal-stem-cell-infused hydrogels, the WFIRM team has found a way to differentiate the cells into chondrocytes and smooth muscle cells.
The cartilage regions of the bioprinted tracheal tissue are stiff and provide support to the structure, while the smooth muscle lends more flexibility and functions to connect the ends of the cartilage rings. The combination of both bioprinted materials allows the tissue to flex and contract, like a human airway.
“People have tried other materials, but the problem has been they were using just one material that is not strong enough to hold the airways open and does not provide the flexibility needed,” explained Sean Murphy, PhD, lead author and assistant professor of regenerative medicine at WFIRM. “Our bioprinting method provides a combination of flexibility and strength needed to mimic native tracheal tissue.”
Down the line, bioprinted tracheal tissue could be used to treat tracheal stenosis, a rare condition or symptom that causes the stiffening and narrowing of the trachea and can lead to death. Presently, treatments for the condition are limited and present their own challenges. Being able to 3D bioprint a patient specific tracheal tissue could therefore present a new and innovative solution.
The novel approach developed by the WFIRM team combines three key areas: patient-specific medical imaging, hydrogels embedded with differentiated cells and polymeric scaffolding with biomechanical-inspired properties. According to Murphy, the research sought to discover if the stem cells could successfully be differentiated in a 3D environment, rather than a 2D one. With the help of growth factors, the team was pleasantly surprised.
“This early proof-of-concept study shows that we can streamline bioprinting capabilities and could someday provide the opportunity for regenerative medicine treatments for the replacement of damaged or diseased tracheal regions,” added Anthony Atala, M.D., director of WFIRM and co-author of the paper. “Next steps in the research would be to evaluate long-term function to ensure appropriate tissue formation and strength retention.”
3D printed stents
Until the bioprinted tissue tracheal solution is clinically ready, there are some other 3D printing solutions that have shown promise for other trachea-related problems. This past October, for instance, Italian company Prosilas 3D printed a stent which was successfully implanted into a five-year-old boy suffering from tracheomalacia, a condition that causes airway collapse and difficulty breathing.
The biocompatible stent, 3D printed using SLS technology, was designed to be resorbed into the patient’s body within two years. Within months of having the 3D printed stent implanted, the young boy has reportedly already seen improvements in his breathing.
A similar treatment was pioneered in 2015, when a team led by Dr. Glenn Green, a pediatric otorhinolaryngology specialist and researcher at the University of Michigan, developed a 3D printed splint for treating tracheobronchomalacia. In many cases, young children or babies suffering from collapsing airways were treated successfully with the customized 3D printed splint.
All that to say that 3D printing has and will continue to play an important role in treating trachea-related issues. Today with resorbable stents and splints, tomorrow with bioprinted tissues!