Evaluating the Impact of Graft Splinting on Fibroblast Recruitment and Collagen Deposition in Airway Reconstruction

Introduction: Stenosis, characterized by airway narrowing, is a common complication following airway reconstruction. Composite tracheal grafts (CTG) have been shown to attenuate airway narrowing while supporting host-derived neo tissue formation. Using a mouse microsurgical model, we aim to investigate the impact of graft splinting on collagen deposition and fibroblast infiltration.

Methods: To create CTG, electrospun splints made of polyglycolic acid (PGA), poly(lactide-co-ε-caprolactone) (PLCL), or PLCL/PGA were combined with a partially decellularized graft (PDTG). CTG or PDTG were then implanted into mice and harvested at 2 weeks post-implantation. All measurements were all made within the midgraft region of the tracheal graft.

Results: The rate of resorption of each splint material is known to be of the following order: PGA (highest), hybrid (intermediate), and PLCL (lowest). Histological analysis revealed no significant difference in the submucosal thickness or collagen deposition among all groups. However, differences in cellular infiltration were observed. Notably, the CTG composed of the splint material (PLCL) with the lowest rate of resorption demonstrated a significant reduction in cellular infiltration within the submucosa compared to the non-splinted PDTG group (p = 0.0057). However, the remaining groups did not show significant differences in cellular infiltration compared to PDTG.

Conclusions: We found that PLCL-based CTG, the material with the lowest rate of resorption among the three splint materials, significantly reduced cellular infiltration compared to non-splinted grafts. Future studies could explore materials with even lower rates of resorption, which may provide more sustained structural support and potentially reduce collagen deposition, submucosal thickness, and airway narrowing over longer time periods.