A Pilot Study of Decellularized Cartilage for Laryngotracheal Reconstruction in a Neonatal Pig Model

Author:

Gehret Paul M.12,Dumas Alexandra A.12,Jacobs Ian N.13,Gottardi Riccardo12345ORCID

Affiliation:

1. Department of Surgery, Division of Otolaryngology Children's Hospital of Philadelphia Philadelphia Pennsylvania U.S.A.

2. Department of Bioengineering, School of Engineering and Applied Science University of Pennsylvania Philadelphia Pennsylvania U.S.A.

3. Department of Otorhinolaryngology Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania U.S.A.

4. Department of Pediatrics, Division of Pulmonary and Sleep Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania U.S.A.

5. Department of Orthopaedic Surgery Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania United States

Abstract

ObjectiveSevere subglottic stenosis develops as a response to intubation in 1% of the >200,000 neonatal intensive care unit infants per year and may require laryngotracheal reconstruction (LTR) with autologous hyaline cartilage. Although effective, LTR is limited by comorbidities, severity of stenosis, and graft integration. In children, there is a significant incidence of restenosis requiring revision surgery. Tissue engineering has been proposed to develop alterative grafting options to improve outcomes and eliminate donor‐site morbidity. Our objective is to engineer a decellularized, channel‐laden xenogeneic cartilage graft, that we deployed in a proof‐of‐concept, neonatal porcine LTR model.MethodsMeniscal porcine cartilage was freeze–thawed and washed with pepsin/elastase to decellularize and create microchannels. A 6 × 10‐mm decellularized cartilage graft was then implanted in 4 infant pigs in an anterior cricoid split. Airway patency and host response were monitored endoscopically until sacrifice at 12 weeks, when the construct phenotype, cricoid expansion, mechanics, and histomorphometry were evaluated.ResultsThe selective digestion of meniscal components yielded decellularized cartilage with cell‐size channels. After LTR with decellularized meniscus, neonatal pigs were monitored via periodic endoscopy observing re‐epithelization, integration, and neocartilage formation. At 12 weeks, the graft appeared integrated and exhibited airway expansion of 4 mm in micro‐CT and endoscopy. Micro‐CT revealed a larger lumen compared with age‐matched controls. Finally, histology showed significant neocartilage formation.ConclusionOur neonatal porcine LTR model with a decellularized cartilage graft is a novel approach to tissue engineered pediatric LTR. This pilot study sets the stage for “off‐the‐shelf” graft procurement and future optimization of MEND for LTR.Level of EvidenceNA Laryngoscope, 134:807–814, 2024

Funder

American Laryngological Association

Children's Hospital of Philadelphia

National Science Foundation

Publisher

Wiley

Subject

Otorhinolaryngology

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