Successful Early Neovascularization in Composite Tracheal Grafts
Sarah C. Nyirjesy, Jane Yu, Sayali Dharmadhikari, Lumei Liu, Maxwell Bergman, Zheng Hong Tan, Kyle K. VanKoevering, Tendy Chiang
Abstract
Abstract Objective Long‐segment tracheal defects require tissue replacement for successful reconstruction. Rapid revascularization is imperative to maintain graft function. We previously showed that partially decellularized tracheal grafts (PDTG) and composite tracheal grafts (CTG; PDTG supported by a 3‐dimensionally printed external splint) regenerate respiratory epithelium and may support the regeneration of endothelial cells (CD31+). However, the capability of graft endothelial cells to organize or contribute to tracheal revascularization remains unclear. In this study, we quantified endothelial cells (CD31+) and neovessel formation in PDTG and CTG. We hypothesize that PDTG and CTG support tracheal neovascularization to a similar extent as surgical (syngeneic tracheal graft [STG]) and native trachea (NT) controls. Study Design The animal study, a randomized control trial. Setting Center for Regenerative Medicine, Nationwide Children's Hospital. Methods PDTG was created via an established decellularization protocol. Segmental tracheal reconstruction was performed with STG, PDTG, or CTG using a mouse microsurgical model. NT was used as a nonsurgical control. At 1 month, mice were euthanized, grafts harvested, sectioned, and stained with CD31 and hematoxylin and eosin. Neovessel formation was quantified by the number of formed blood vessels in the lamina propria and vessel size (vessel/graft area, mm 2 ). Results Decellularization eliminated all endothelial cells and there were no perfused vessels at implantation. At 1 month, PDTG and CTG supported neovessel formation with tubular vessels lined with endothelial cells. There was no difference in the number or size of vessels compared to controls. Conclusion PDTG and CTG support tracheal endothelial cell regeneration and neovessel formation. Future directions to assess the function, kinetics, and distribution of graft neovessels are needed.