Just home from the hospital, Melissa’s infant son sounded raspy when breathing, as if he constantly fought congestion, even though he didn’t.
Born two and a half months early, Grant was in a regional hospital’s NICU for two months, and during that time he developed an E. coli infection that required him to be intubated with a breathing tube to support his lungs and on an oscillating ventilator for more than three weeks. Once the tube was removed, his breathing sounded labored.
Doctors would later discover that Grant had a narrower than normal subglottis, the smallest part of the airway. A narrow subglottis is not unusual for children born prematurely, and Grant’s was further narrowed by scarring from an extended intubation.
Days before a December surgery to expand Grant’s airway, Melissa became alarmed that her son was gasping and panicking as he tried to breathe.
“I’ve never been more scared in my life,” she says.
Grant was given breathing treatments that stabilized him at a local hospital. Then he was driven by ambulance to Nationwide Children’s Hospital. There Jonathan M. Grischkan, MD, MS, performed the surgery to expand his subglottis by removing a piece of his own rib cartilage and grafting it onto his subglottis to expand the airway size and allow him to breathe more easily. As Grant grows, his subglottis is expected to widen with him.
Now 15 months old, Grant is far more active than he ever was. He crawls, plays, lifts himself up, babbles constantly and screams.
“He doesn’t sound like a raspy little old man anymore,” Melissa says.
Grant’s ability to breathe is no longer a source of constant worry for his mother, who spent nights wondering if her infant son might stop breathing.
Grant’s airway defect was acquired because he was born prematurely and intubated for an extended period of time. Fortunately, his defect was able to be repaired with a first-line approach.
Many airway defect repairs aren’t so straightforward.
Airway reconstructions are complicated procedures performed to expand or repair the airway anatomy, including the trachea, in a patient whose airway is compromised because of congenital malformation or injury. While congenital malformations of the airway are rare and often caught too late, numerous patients have long-term tracheotomies. Additionally, a catastrophic defect can be acquired through scarring due to intubation, inhalation injuries or trauma.
“When more than 30 percent of a child’s airway is affected, these defects exceed the capabilities of conventional techniques for reconstructing the airway,” says Tendy Chiang, MD, pediatric otolaryngologist at Nationwide Children’s. “When you get to that point, there aren’t a lot of good options, and sometimes, you run out of options entirely.”
But Dr. Chiang and a team of researchers at Nationwide Children’s want to change that. Through regenerative medicine Dr. Chiang is working to develop tissue-engineered airway replacements that would be seeded with the patient’s own stem cells, resulting in a graft that would grow with the patient, permanently fixing the defect.
“We are taking information from our decades of research and the fairly recent human procedures that have been done and working out the problems in the animal models,” says Dr. Chiang, who is also principal investigator in the Tissue Engineering Program in The Research Institute at Nationwide Children’s. “It’s about taking research from the bench to the bedside and back to the bench.”
To build a tissue-engineered trachea, Dr. Chiang and his team use a scaffold produced by Nanofiber Solutions and seed it with bone marrow-derived mononuclear cells. The collection of the cells, the seeding and implantation happens in a matter of hours.
“While there are many approaches to seeding a scaffold and growing a trachea, we are applying easily translatable methods that will permit our procedure to be performed in the operating room,” explains Dr. Chiang, who is also an assistant professor in the Department of Otolaryngology at The Ohio State University College of Medicine. “We are using the body as a bioreactor.”
Dr. Chiang’s trachea research is part of a larger effort in tissue engineering led by Christopher Breuer, MD, pediatric surgeon and principal investigator in the Center for Cardiovascular Research in The Research Institute at Nationwide Children’s.