First-in-human Study of Biotube Vascular Grafts: A 2 Year Follow-up in A Bypass Model of Stenosed AV Shunt

Abstract

Introduction - An arteriovenous (AV) fistula is the current gold standard for chronic hemodialysis access. However, a substantial number of shunt will fail because of stenosis or obstruction at anastomotic site or venous outflow. Tissue-engineered blood vessels have been proposed for dialysis access as an alternative to prosthetic grafts. We developed autologous collagenous tubular tissues Biotubes based on in-body tissue architecture (iBTA), which is a novel regenerative medicine technology by using a patient's body as a bioreactor. This report presents the results in the first-in-human study up to 2 year follow-up in the first two patients bypassed with an autologous Biotube. Methods - Two female patients had end-stage renal disease and had been receiving heamodialysis with a high probability of failure, because of repeatable stenosis about every 2 or 3 months at venous outflow regions over 1 year. Biotube with 5 or 6 mm in diameter and 7 cm in length (2 in photos) was prepared as autologous collagenous tubular tissues with wall thickness of ca. 1 mm by subcutaneous embedding of the molds (1 in photos), assembled with a silicone center rod and a stainless steel pipe, into patients abdominal pouches for 2 months. Results -The Biotubes after stored for 1 day in a 70% alcohol solution and washing with a saline solution before surgery were bypassed by end-to-side anastomoses over venous stenosis region of an AV shunt (3 in photos). Palpable thrill and typical turbulent flow pattern by pulsed-wave Doppler were observed. Monthly angiography showed little change in the implanted grafts with no signs of dilation or stenosis with time points up to 3 months (4 in photos). Although shortening of the Biotubes occurred, dialysis was possible without requiring balloon expansion for 2 years. Conclusion - This long-term follow up study successfully supported the concept of creating dialysis access by Biotube grown in patient’s subcutaneous pouches.