Long-Term Chondrocyte Retention in Partially Decellularized Tracheal Grafts

Otolaryngol Head Neck Surg. 2024 Jan;170(1):239-244. doi: 10.1002/ohn.409. Epub 2023 Jun 27.

Abstract

Objective: Decellularized tracheal grafts possess the biological cues necessary for tissue regeneration. However, conventional decellularization approaches to target the removal of all cell populations including chondrocytes lead to a loss of mechanical support. We have created a partially decellularized tracheal graft (PDTG) that preserves donor chondrocytes and the mechanical properties of the trachea. In this study, we measured PDTG chondrocyte retention with a murine microsurgical model.

Study design: Murine in vivo time-point study.

Setting: Research Institute affiliated with Tertiary Pediatric Hospital.

Methods: PDTG was created using a sodium dodecyl sulfate protocol. Partially decellularized and syngeneic grafts were orthotopically implanted into female C57BL/6J mice. Grafts were recovered at 1, 3, and 6 months postimplant. Pre- and postimplant grafts were processed and analyzed via quantitative immunofluorescence. Chondrocytes (SOX9+, DAPI+) present in the host and graft cartilage was evaluated using ImageJ.

Results: Partial decellularization resulted in the maintenance of gross tracheal architecture with the removal of epithelial and submucosal structures on histology. All grafts demonstrated SOX9+ chondrocytes throughout the study time points. Chondrocytes in PDTG were lower at 6 months compared to preimplant and syngeneic controls.

Conclusion: PDTG retained donor graft chondrocytes at all time points. However, PDTG exhibits a reduction in chondrocytes at 6 months. The impact of these histologic changes on cartilage extracellular matrix regeneration and repair remains unclear.

Keywords: chondrocyte viability; regenerative medicine; tissue engineering; tracheal replacement.

MeSH terms

  • Animals
  • Cartilage / transplantation
  • Child
  • Chondrocytes* / transplantation
  • Female
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Tissue Engineering / methods
  • Tissue Scaffolds / chemistry
  • Trachea* / surgery