Bioengineering Scientists Creating Cartilage Implants for Severe Subglottic Stenosis

By Emily Shafer

Bioengineering researchers at Children’s Hospital of Philadelphia are developing a less invasive and quicker method to create cartilage implants as an alternative to the current treatment for severe subglottic stenosis, which occurs in 10 percent of premature infants in the U.S.

Subglottic stenosis is a narrowing of the airway, in response to intubation. Severe cases require laryngotracheal reconstruction that involves grafting cartilage from the rib cage with an invasive surgery. With grant support from the National Institutes of Health, Riccardo Gottardi, PhD, who leads the Bioengineering and Biomaterials (Bio²) Lab at CHOP, is refining a technology called Meniscal Decellularized scaffold (MEND). Working with a porcine model meniscus, the researchers remove blood vessels and elastin fibers to create pathways that allow for recellularization. Dr. Gottardi and his team then harvest ear cartilage progenitor cells (CPCs) with a minimally invasive biopsy, combine them with MEND, and create cartilage implants that could be a substitute for the standard laryngotracheal reconstruction.

This work and similar work on the tympanic membrane earned Paul Gehret, a doctoral student in the Gottardi Lab, the International Society for Biofabrication New Investigator Award and the Wake Forest Institute for Regenerative Medicine Young Investigator Award.  Gehret and Dr. Gottardi accepted the awards at Biofabrication 2022, the International Conference on Biofabrication, in Pisa Italy.

While laryngotracheal reconstruction in the adult population has a success rate of up to 96%, success rates in children range from 75% to 85%, and children often require revision surgery due to a high incidence of restenosis. The procedure also involves major surgery to remove cartilage from the rib cage, which is more difficult for childrens’ smaller bodies. 

“Luckily not many children suffer from severe subglottic stenosis, but for those who do, it is really serious,” said Dr. Gottardi, who also is assistant professor in the Department of Pediatrics and Department of Bioengineering at CHOP and the University of Pennsylvania. “With our procedure, we have an easily accessible source for the cartilage and the cells, providing a straightforward and noninvasive treatment option with much potential.”

Severe subglottic stenosis results from formation of scar tissue in the airway. Most scar tissue resolves on its own, but scar tissue in severe subglottic stenosis continues to build up and closes off the airway. For laryngotracheal reconstruction, surgeons take a piece of cartilage from the rib cage and use it as a spacer. A disadvantage with this approach is that the children require tracheotomy tubes to breathe until they are physically big enough to have the surgery. Existing technological options to create cartilage in the lab can take as long as six months to grow the tracheal cartilage, but children are usually ready for surgery within two months after diagnosis.

Dr. Gottardi’s goal is to leverage novel bioengineering approaches to create cartilage that is mechanically robust to act as the spacer. Ear cartilage progenitors are ideal because they can be harvested easily, with a minimally invasive biopsy, and they grow fast — within 10 days, there are enough to engineer the cartilage. The MEND technology removes unnecessary elements from the porcine model meniscal cartilage, leaving a physical material that has ideal properties to host the cartilage progenitors.

“This is an innovative procedure that grows robust cartilage within three weeks in the lab,” Dr. Gottardi said. “The decellularized porcine model meniscus has good mechanics to start, and when you add the cartilage progenitors, it has properties that match those of the native tracheal cartilage.” 

If the preclinical studies are successful, future clinical studies will be implemented before the bioengineered cartilage implants could be used to help children with severe subglottic stenosis.