Assessing the Impact of Partial Decellularization on Tracheal Chondrocytes and Extracellular Matrix in Airway Reconstruction.

Abstract

Partially decellularized tracheal grafts (PDTG) are potential candidates for tracheal replacement as they support neotissue formation without stenosis or rejection. However, the effects of partial decellularization (PD) on extracellular matrix (ECM) and chondrocytes are not currently understood, limiting PDTG translatability for clinical use. We aim to quantify the impact of PD on trachea using mouse and rabbit models. An animal model. Research Institute affiliated with a Tertiary Pediatric Hospital. PDTG and syngeneic tracheal grafts (STG) were implanted orthotopically in mice for 1 month (N = 10/group). Grafts were analyzed with mechanical testing, chondrocyte viability, and protein integrity. We tested the scalability of PDTG at a pediatric scale using a rabbit model at 3- and 6-month timepoints (N = 3/timepoint). Histologic and radiographic analyses were performed to assess chondrocyte viability and neotissue formation. Rabbit PDTG and native chondrocytes were isolated and cultured assessing PD effect on proliferation. PD of mouse trachea eliminated all epithelial cells, maintained chondrocyte viability, and did not reduce graft mechanical properties or ECM proteins. Overall, collagen and glycosaminoglycans had similar expression and integrity in PDTG and STG. PDTG retained graft patency and supported epithelialization and vascularization. Like mice, PD of rabbit trachea achieved these goals, but had increased radiodensity. Unlike mice, rabbit PDTG had greater chondrocyte and ECM loss in vivo. Unique to rabbits, PD reduced chondrocyte proliferation in vitro compared to native chondrocytes. Despite similar pre-implantation metrics to the successful mouse model and support of neotissue formation, human-scale PDTG demonstrated greater chondrocyte and ECM loss.