Biomaterial Selection Regulates Tissue Remodeling and Collagen Deposition in Composite Tracheal Grafts.

Abstract

Airway collapse is a life-threatening complication of tracheal grafting, yet no definitive strategy to prevent this exists. Composite tracheal grafts (CTG) that incorporate biodegradable splints can promote structural support and host integration. This study evaluated how electrospun splint composition modulates submucosal remodeling and collagen deposition in partially decellularized tracheal grafts (PDTG). Case-control study using a microsurgical mouse model. Research institute affiliated with a tertiary pediatric hospital. PDTG were orthotopically implanted onto mice trachea. To create CTG, electrospun splints composed of polyglycolic acid (PGA), poly(l-lactide-co-ε-caprolactone) (PLCL), or a PGA/PLCL hybrid were integrated onto PDTG. Grafts were harvested at 2 weeks. Splint resorption, submucosal thickness, and collagen deposition were accessed via quantification of Masson's trichrome images. Cellular infiltration and fibroblast recruitment were evaluated using DAPI and vimentin immunofluorescence, respectively. Quantification was completed in the midgraft region using ImageJ, and statistical analysis was performed using GraphPad Prism 10. Splints demonstrated clear differences in the degree of resorption at 2 weeks. PGA splints demonstrated the greatest resorption, PLCL the lowest, and hybrid PGA/PLCL an intermediate degree. Compared to PDTG alone, PGA and PLCL splints resulted in decreased submucosal thickness, while collagen deposition was increased only in the PGA splint composition. Vimentin staining confirmed fibroblast recruitment into the submucosal layer, which qualitatively varied with biomaterial type. Electrospun biodegradable splints exhibited degradation dynamics and influenced tissue remodeling of engineered tracheal grafts. Material selection may improve graft integration and long-term viability.