ASPO045 - An Engineered Cartilage Approach to Laryngotracheal Reconstruction for Subglottic Stenosis in a Rabbit Model
Saturday, April 30, 2022
4:00 PM – 5:00 PM CT
Location: Landmark B
Paul M. Gehret, B.Sc.1, Ryan C. Borek, M.D.2, Soheila Ali Akbari Ghavimi, Ph.D.3, Alexandra A. Dumas, B.Sc.1, Ian N. Jacobs, M.D.2, Riccardo Gottardi, Ph.D.4;
1Bioengineering, Univ. of Pennsylvania, Philadelphia, PA, 2Otolaryngology, Children's Hosp. of Philadelphia, Philadelphia, PA, 3Harvard Univ., Boston, MA, 4Pulmonary Medicine, Children's Hosp. of Philadelphia, Philadelphia, PA.
Graduate Student University of Pennsylvania University of Pennsylvania
Introduction: In laryngotracheal reconstruction (LTR) surgery to treat pediatric subglottic stenosis, autologous costal cartilage is harvested, shaped, and implanted into the child’s airway. While this surgical treatment is effective, long operation times, donor site morbidly, and insufficient graft materials may cause airway restenosis, necessitating revision surgery. Our objective is to test the feasibility of engineered cartilage for LTR that can provide an abundance of readily available graft material.
Methods: We develop two scaffolds for cartilage engineering: a porous poly-l-lactic acid (PLLA) and a decellularized pig meniscal cartilage. The PLLA scaffold was created by thermally induced phase separation to ensure small pores that support chondrogenesis. The decellularized meniscal pig cartilage was treated with pepsin and elastase to create microchannels for cellular reinvasion. Each scaffold was tested in compression to compare mechanical properties with native cartilage. Suturability was assessed by tensile testing of sutures to failure. The scaffold was then used in our pilot study on 4 rabbits where it was implanted in an anterior cricoid split. After 3 months, the construct phenotype, cricoid expansion, histomorphometry were evaluated.
Results: For PLLA scaffolds uniform recellularization took up to a week, whereas decellularized meniscal cartilage was uniformly recellularized by day 3. In compression, PLLA performed better than decellularized cartilage, although both were within 50% of cricoid cartilage. Decellularized cartilage was easier to suture, and resisted suture pull-through. Overall, decellularized cartilage was selected as best performing graft. Post 3 months, rabbit endoscopy revealed visually integrated and epithelialized grafts that expanded the airway an average of 4 mm. Histology revealed significant formation of neocartilage in the graft and integration with cut cricoid and tracheal rings.
Conclusion: We showed the feasibility of an engineered cartilage using approaches with decellularized and synthetic scaffolds to perform LTR. This innovative engineered graft technology may provide an easy and rapidly available cartilage option for use during LTR. Further pre-clinical animal studies will serve to translate this technology to pediatric patients.