IN VIVO TISSUE ENGINEERED VASCULAR GRAFTS ADAPTABLE TO AV SHUNTS

We have developed autologous in vivo tissue engineered vascular grafts (in vivo TEVG, i.e. BIOTUBE) mainly composed of fibroblasts and collagen constructed in the patients' subcutaneous tissues. After long term animal experiments over 5 years, we clinically applied them to the congenital heart surgery of a 2-year-old child as a pulmonary artery patch plasty material in 2015. Three years after implantation, 3D-CT exhibited neither aneurysmal dilatation, significant calcification, nor shrinkage of the patch graft interfering the growth of the pulmonary artery. The clinical course was good without any significant complications over 4 years presently. However, since the tissue formation largely depends on the regenerative ability of the host, individual differences exist, and it is an issue to secure the mechanical reliability of the grafts formed in high-risk patients. We are currently evaluating the changes in mechanical properties of TEVGs by chemical treatment, and are examining whether it is possible to improve mechanical durability. In addition, in order to fabricate the TEVGs in healthy individuals as allogeneic (parents) or xenogeneic tissue substitutes, we are conducting transplantation experiments on decellularized tissues. The in vivo TEVGs could also be applied to AV-shunts. However, in the animal pilot experiments, significant stenosis was observed at the anastomosis with host vein resulting in early occlusion probably because of high sheer stresses. The attempts to overcome the problems by several investigators are also reviewed.