Initial 3-year results of first human use of an in-body tissue-engineered autologous “Biotube” vascular graft for hemodialysis

Abstract

This study presents the initial 3-year results of the first in-human study of internal shunt restoration using completely autologous vascular grafts, “Biotubes,” based on in-body tissue architecture. Biotubes (diameter, 6 mm; length, 7 cm) were prepared as autologous collagenous tubular tissues with approximately 0.5 mm wall thickness by embedding molds (two per patient), assembled with a silicone rod and a stainless steel pipe with many slits, into the patients’ abdominal subcutaneous tissue for 2 months. Two female patients with end-stage renal disease were undergoing hemodialysis with a high probability of failure due to repeated stenosis every few months at the venous outflow regions over 1.5 years. Biotubes formed in both patients and were bypassed over the venous stenosis region of the arteriovenous shunt. After bypass with Biotubes without living cells, palpable thrill and typical turbulent flow pattern were observed by pulsed-wave Doppler. Follow-up angiography showed no signs of dilation or stenosis after implantation, and puncture could be performed easily without graft damage. In both cases, stenosis of Biotubes occurred after 3–4 months. In the first case, percutaneous transluminal angioplasty was not required for over 2 years after implantation even after the development of Biotube stenosis. In the second case, stenosis at the proximal anastomotic site of the Biotube became prominent, and percutaneous transluminal angioplasty was needed 7 months after implantation and then repeated at up to 2 years. This was the first human study successfully supporting the concept of internal shunt restoration for hemodialysis using an autologous Biotube.

A tissue‐engineered, decellularized, connective tissue membrane for allogeneic arterial patch implantation

“…Aiming to fabricate an ideal vascular graft, multiple tissueengineered vascular grafts (TEVGs) have been developed using in vitro and/or in vivo tissue engineering technology, some of which have been clinically applied. 3,5,6,15 In vivo tissue engineering uses the patient's body as a bioreactor. Several groups have reported the development of a vascular graft that exploits the encapsulation that occurs when foreign materials are implanted under the skin.…”

Freeform 3D printing of vascularized tissues: Challenges and strategies

“…The research team also confirmed the use of Biotubes in clinical practice. 67 Biotubes with diameters of 6 mm and total lengths of 7 cm were similarly produced by implantation for 2 months in the abdominal subcutaneous tissue of patients who were undergoing hemodialysis. Although the implanted Biotubes led to stenosis for patients 4 months after the first surgery, this study has clinical significance because the first human case study was performed using autologous vascular constructs prepared by a molding technique.…”

iBTA-Induced Biotube® Blood Vessels: 2020 Update

“…Since its conception, the first developed mold as Biotube Maker has been a straight columnar type (original mold in Figure 1a), which is assembled by covering the outside of a plastic core rod with a stainless steel pipe with a predetermined gap space [30,35]. The pipe contains many thin slits.…”

“…Biotubes obtained from the straight mold have already been clinically applied to three dialysis patients as a First-in-Man (FIM) study [35]. Blood vessels on the venous side of the arteriovenous shunt are prone to stenosis.…”