LAUSR

OBJECTIVE Vascular conduit is essential for arterial reconstruction for a number of conditions, including trauma and atherosclerotic occlusive disease. We have developed a tissue-engineered human acellular vessel (HAV) that can be manufactured, stored on site at hospitals, and be immediately available for arterial vascular reconstruction. Although the HAV is acellular when implanted, extensive preclinical and clinical testing has demonstrated that the HAV subsequently repopulates with the recipient's own vascular cells. We report a first-in-man clinical experience using the HAV for arterial reconstruction in patients with symptomatic peripheral arterial disease. METHODS HAVs were manufactured using human vascular smooth muscle cells grown on a biodegradable scaffold. After the establishment of adequate cell growth and extracellular matrix deposition, the vessels were decellularized to remove human cellular antigens. Manufactured vessels were implanted in 20 patients with symptomatic peripheral arterial disease as above-knee, femoral-to-popliteal arterial bypass conduits. After HAV implantation, all patients were assessed for safety, HAV durability, freedom from conduit infection, and bypass patency for 2 years. RESULTS Twenty HAVs were placed in the arterial, above-knee, femoral-to-popliteal position in patients with rest pain (n = 3) or symptomatic claudication (n = 17). All HAVs functioned as intended and had no evidence of structural failure or rejection by the recipient. No acute HAV infections were reported, but three surgical site infections were documented during the study period. Three non-HAV-related deaths were reported. One vessel developed a pseudoaneurysm after suspected iatrogenic injury during a balloon thrombectomy. No amputations of the HAV implanted limb occurred over the 2-year period, and no HAV infections were reported in approximately 34 patient-years of continuous patient follow-up. CONCLUSIONS Human tissue engineered blood vessels can be manufactured and readily available for peripheral arterial bypass surgery. Early clinical experience with these vessels, in the arterial position, suggest that they are safe, have acceptable patency, a low incidence of infection, and do not require the harvest of autologous vein or any cells from the recipient. Histologic examination of tissue biopsies revealed vascular remodeling and repopulation by host cells. This first-in-man arterial bypass study supports the continued development of human tissue engineered blood vessels for arterial reconstruction, and potential future expansion to clinical indications including vascular trauma and repair of other size-appropriate peripheral arteries.