Development of xenogeneic decellularized biotubes for off‐the‐shelf applications

Abstract

In earlier studies, we developed in vivo tissue‐engineered, autologous, small‐caliber vascular grafts, called “biotubes,” which withstand systemic blood pressure and exhibit excellent performance as small‐caliber vascular prostheses in animal models. However, biotube preparation takes 4 weeks; therefore, biotubes cannot be applied in emergency situations. Moreover, for responses to various types of surgery, grafts should ideally be readily available in advance. The aim of this study was to develop novel, off‐the‐shelf, small‐caliber vascular grafts by decellularizing in vivo tissue‐engineered xenogeneic tubular materials. Silicone rod molds (diameter: 2 mm, length: 70 mm) placed in subcutaneous pouches of a beagle dog for 4 weeks were harvested with their surrounding connective tissues. Tubular connective tissues were obtained after pulling out the impregnated molds. Subsequently, they were decellularized by perfusion with sodium dodecyl sulfate and Triton X‐100. They were stored as off‐the‐shelf grafts at −20°C for 1 week. The decellularized grafts derived from the beagle dog were xenogeneically transplanted to the abdominal aortas of rats (n = 3). No signs of abnormal inflammation or immunological problems due to the xenogeneic material were observed. Echocardiography confirmed the patency of the grafts at 1 month after implantation. Histological evaluation revealed that the grafts formed neointima on the luminal surface, and that the graft walls had cell infiltration. Little accumulation of CD68‐positive macrophages in the graft wall was observed. Xenogeneic decellularized tubular tissues functioned as small‐caliber vascular grafts, as well as autologous biotubes. This technology enables the easy fabrication of grafts from xenogeneic animals in advance and their storage for at least a week, satisfying the conditions for off‐the‐shelf grafts.

Scaffold‐free tissue‐engineered arterial grafts derived from human skeletal myoblasts

“…30 Against this background, recent studies tried to modify the decellularization protocols to improve the biocompatibilities. 32,33 In the present study, the myoblast grafts did not require decellularization process, which support the feasibility of human skeletal myoblasts as a cell source for TEVGs.…”

Modifications of the mechanical properties of in vivo tissue-engineered vascular grafts by chemical treatments for a short duration

“…To conclusively overcome the issue of the individual variety of the tissue regeneration in vivo, we need to investigate additional options. We also began another approach using more reliable tissues derived from healthy individuals via allogeneic or xenogeneic transplantation [30]. Second, further investigation of their long-term biological performance is very important.…”

Systematic Review of Tissue-Engineered Vascular Grafts

“…Nevertheless, mechanical properties, such as suture strength, are not sufficient for clinical use ( Reinhardt et al, 2019 ). Another technology, known as “biotubes,” involves the development of blood vessels by subcutaneous implantation, and is associated with a biological defense mechanism ( Rothuizen et al, 2016 ; Tseng et al, 2017 ; Furukoshi et al, 2019 ; Yamanami et al, 2019 ). Finally, some authors used the innovative 3D bioprinting technique to manufacture TEVGs ( Itoh et al, 2015 ; Itoh et al, 2019 ; Jang et al, 2020 ).…”