Experimental Study On BMP-induced Cartilage Regeneration In Tracheal Grafts

Tracheal transplantation is one of the important anticipated events in tracheal surgery, being regarded as an ideal method for reconstruction of tracheal defect after extensive resection. The research on tracheal transplantation progressed slowly in the past years because of the subsequent severe stenosis and obliteration of the tracheal grafts. The major causes consisted of ischemia and rejection of tracheal grafts, which result in cartilaginous necrosis, chondrolysis and resorption. Although different processes of airway collapse'have been found in tracheal grafts treated by different methods, few suitable methods can be applied to solve the problem essentially up to date. So it's necessary to find a new method to prevent the tracheal grafts from stenosis. Bone morphogenetic proteins (BMPs) are a group of proteins which can induce new cartilage and/or bone formation heterotopically, and in this study BMP was used to meet the problem.Objective: Aim to induce cartilage regeneration in tracheal grafts by utilizing the osteogenesis character of BMP, and ultimately aim to form a new elastic stent for tracheal grafts to protect the airway from collapse.Methods: Canine tracheal transplantation models were used to observe the correlated factors of stenosis, and then BMP was implanted into the canine tracheal auto- and allo- grafts to induce cartilage regeneration. In the experiment two transplantation methods were used, reimplanted and then wrapped with pedicled omentum or transplanted heterotopically into the omentum, and different carriers for BMP and different doses of BMP were also used. Conditions of animals, gross and pathological characters of thespecimens, and newly formed cartilage were compared among the different groups.Results: Stenosis of tracheal grafts was closely correlated with epithelial regeneration and cartilage morphological maintenance. Cartilage rings were absorbed with varying degree in all tracheal autografts and allografts, and new cartilage was induced in the BMP injected area. Better cartilage structure was maintained and more new cartilage was induced when the grafts were transplanted heterotopically than that of orthotopically. The quantities of newly formed cartilage were different when different carriers for BMP or different doses of BMP were used.Conclusions: (1) BMP could induce new cartilage regeneration in the tracheal auto- and allo- graft, and was more effective when transplanted heterotopically into the omentum. Immunosuppressant would be beneficial for cartilage regeneration in allograft. (2) Both PVP and collagen could be used as carriers for rhBMP-2 to induce cartilage regeneration in the tracheal autografts, and collagen was more effective than other carriers to induce cartilage regeneration in tracheal transplantation. (3) The rhBMP-2 caused a dose-dependent increase in newly formed cartilage. 5 mg would be an appropriate dose for rhBMP-2 with a collagen carrier injected into the soft tissue between cartilaginous rings in the canine tracheal autografts.