Long-term results of autologous scaffold-free tissue-engineered vascular graft for hemodialysis access

Abstract

Background: The growing size of the end stage renal disease (ESRD) population highlights the need for effective dialysis access. Exhausted native vascular access options have led to increased use of catheters and prosthetic shunts, which are both associated with high risks of access failure and infection. Emerging alternatives include tissue-engineered vascular grafts (TEVG). Here we present the endpoint results for 10 ESRD patients with the scaffold-free tissue-engineered vascular access produced from sheets of extracellular matrix produced in vitro by human cells in culture. Methods: Grafts were implanted as arteriovenous shunts in 10 ESRD patients with a complex history of access failure. Follow-up included ultrasound control of graft morphology and function, dialysis efficiency, access failure, intervention rate, as well as immunohistochemical analysis of graft structure. Results: One patient died of unrelated causes and three shunts failed to become useable access grafts during the 3-month maturation phase. The 12-month primary and secondary patency for the other six shunts was 86%. Survival of six shunts functioning as the vascular access was 22 ± 12 months with longest primary patency of 38.6 months. The dialysis event rate of 3.34 per patient-year decreased significantly with the use of this TEVG to 0.67. Conclusions: This living autologous tissue-engineered vascular graft seems to be an alternative to synthetic vascular access options, exhibiting advantages of native arteriovenous fistula.

Development and characterization of biological sutures made of cell-assembled extracellular matrix

“…However, these synthetic materials are recognized as foreign bodies and generate inflammatory reactions [6][7][8]. In this study, we developed an innovative suture made of a non-denatured biological material that has already shown superior biological properties in humans (tissue integration, remodeling, resist infection, and does not elicit an immune response) [26][27][28]. After characterizing the mechanical properties of hydrated CAM-based ribbons, we have shown that twisted/dried ribbons obtained from CAM sheet can be attached to an eyeless surgical needle to produce biological sutures using a standard manufacturing approach (video 1).…”

“…This material, called Cell-Assembled extracellular Matrix (CAM), is produced in large culture flasks as a sheet, which can be cut into ribbons that can be assembled in biological textiles [21,22,25]. This biomaterial was successfully implanted in humans as tubes for vascular applications [26][27][28]. Implantation results validated the hypothesis that this completely biological material can integrate with native tissue, be remodeled by the host's cells, and resist infection.…”

Development of a vascular substitute produced by weaving yarn made from human amniotic membrane

“…While there will always be a protein turnover in a biological matrix, the strategy is to have a very slow degradation to allow the body to colonize and remodel the graft before it loses mechanical integrity. This was achieved to some degree using autologous and allogeneic, rolled, CAMbased TEVG [16,17,40].…”

Anti-Inflammatory and Anti-Thrombogenic Properties of Arterial Elastic Laminae

“…In particular, cell-sheet-based approaches have been used to produce natural blood-vessel-like constructs, some of which have been tested in clinical trials with excellent results [ 108 ]. For example, long-term results from a recent human study with a cell-sheet-derived graft for hemodialysis access showed great promise as an alternative to synthetic grafts [ 109 , 110 ]. However, these approaches require tedious and complex culture and maturation processing.…”