A translational approach to airway reconstruction leveraging decellularized meniscus and cartilage progenitor cells

Severe subglottic stenosis develops in over 20,000 infants per year and requires laryngotracheal reconstruction to enlarge the airway by implanting autologous cartilage from a rib graft. However, young children often lack sufficiently sized costal cartilage for this procedure, resulting in increased donor site morbidity and operative time, as well as an elevated risk for airway restenosis, necessitating revision surgery. To overcome these limitations, we create a scaffold based on porcine meniscal cartilage decellularization - which we term MEND - by selectively digesting away the elastin and blood vessels uniquely present in the meniscus; this creates microchannels that support cellular re-invasion. Here we demonstrate that MEND can be fully recellularized in 3 days with ear-derived cartilage progenitor cells and reaches structural and functional maturation suitable for implant within 3 weeks of chondrogenic differentiation, a time frame compatible with clinical translation. To further this therapy toward clinical translation, we validate the ear-derived cartilage progenitor cell-MEND grafts in a New Zealand white rabbit laryngotracheal reconstruction model. Our results demonstrate airway expansion, graft re-epithelialization, neocartilage formation, and integration with adjacent native laryngotracheal cartilage at 3 months. Notably, MEND implants perform better in all outcomes than autologous costal cartilage, the standard of care. No instances of adverse events such as extrusion, granulation, infection, or calcification are observed in any of the 38 rabbits in our study. These results demonstrate the feasibility of our translational tissue engineering approach to laryngotracheal reconstruction and could overcome the autograft-associated limitations in pediatric patients, decreasing the need for invasive revision surgery.