title: Reconstruction of Anterior Tracheal Defects Using a Bioengineered Graft in a Porcine Model.
abstract: BACKGROUND
  Reconstruction of long-segment tracheal defects can be challenging and a suitable tracheal substitute remains lacking. We sought to create a bioengineered tracheal graft to repair such lesions using acellullar bovine dermis extracellular matrix (ECM) and male human mesenchymal stem cells (hMSCs) and implant it in a porcine model.
  
  
  METHODS
  hMSCs were seeded on the ECM and incubated for 1 week with chondrogenic factors. An anterior 4 cm × 3 cm defect was surgically created in the trachea of 4-week-old female Yorkshire pigs. The defect was reconstructed using the bioengineered graft (n = 7) or control (n = 3, ECM only). The study duration was 3 months.
  
  
  RESULTS
  Survival ranged from 7 days (n = 3) to 3 months (n = 7). Early death was due to graft malacia (n = 1, control), graft infection (n = 1, bioengineered), and pneumonia (n = 1, bioengineered). There was substantial animal growth at 3 months (>200% weight). Surveillance bronchoscopy showed patent airway, mild stenosis, and integration of the graft with the native trachea. On histology, luminal epithelialization and neovascularization with scant submucosa were observed in both the bioengineered graft and control groups. Chondrogenesis was seen only in the bioengineered graft. The neocartilage was less mature and organized compared to native cartilage. SRY immunostain was positive in the neocartilage but not control or native trachea.
  
  
  CONCLUSIONS
  We demonstrate the feasibility of the bioengineered graft for reconstruction of long anterior tracheal defects with favorable short-term outcomes. Furthermore, we show its ability to facilitate chondrogenesis, neovascularization, and epithelialization. Importantly, it supported rapid animal growth offering potential solutions for both pediatric and adult applications.
authors.affiliation: Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, New York.
authors.forename: Adnan M
authors.initials: AM
authors.lastname: Al-Ayoubi
authors.affiliation: Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, New York.
authors.forename: Sadiq S
authors.initials: SS
authors.lastname: Rehmani
authors.affiliation: Department of Ear, Nose and Throat-Head and Neck Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, New York.
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Sinclair
authors.affiliation: Department of Ear, Nose and Throat-Head and Neck Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, New York.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Lebovics
authors.affiliation: Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, New York. Electronic address: fybhora@chpnet.org.
authors.forename: Faiz Y
authors.initials: FY
authors.lastname: Bhora
mesh_terms: D062088:Acellular Dermis; D000818:Animals; D002417:Cattle; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D019651:Plastic Surgery Procedures / Q000379:methods*; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014132:Trachea / Q000601:surgery*; D014135:Tracheal Stenosis / Q000601:surgery*