Combination of inductive effect of lipopolysaccharide and in situ mechanical conditioning for forming an autologous vascular graft in vivo

Chao-Lin Chen,Chao-Yi Chen,Hsiu-Chuan Lin,Hong-Tai Chang,Jin-Jia Hu,Chui-Yi Pan,Ying-Jan Wang,Ho-Yi Tuan-Mu,How-Ran Guo

doi:10.1038/s41598-019-47054-2

Abstract

Autologous vascular grafts have the advantages of better biocompatibility and prognosis. However, previous studies that implanted bare polymer tubes in animals to grow autologous tubular tissues were limited by their poor yield rates and stability. To enhance the yield rate of the tubular tissue, we employed a design with the addition of overlaid autologous whole blood scaffold containing lipopolysaccharides (LPS). Furthermore, we applied in vivo dynamic mechanical stimuli through cyclically inflatable silicone tube to improve the mechanical properties of the harvested tissues. The effectiveness of the modification was examined by implanting the tubes in the peritoneal cavity of rats. A group without mechanical stimuli served as the controls. After 24 days of culture including 16 days of cyclic mechanical stimuli, we harvested the tubular tissue forming on the silicone tube for analysis or further autologous interposition vascular grafting. In comparison with those without cyclic dynamic stimuli, tubular tissues with this treatment during in vivo culture had stronger mechanical properties, better smooth muscle differentiation, and more collagen and elastin expression by the end of incubation period in the peritoneal cavity. The grafts remained patent after 4 months of implantation and showed the presence of endothelial and smooth muscle cells. This model shows a new prospect for vascular tissue engineering.

Highlights

Vascular grafts are needed for many clinical conditions such as coronary artery disease, end-stage renal disease, and peripheral artery occlusion disease
IHC staining of the LPS of the blood scaffold showed that the applied LPS was distributed throughout the scaffold and luminal surface (Fig. 1b-1), negative control with non-immune isotype IgG was shown as Fig. 1b-2
It was reported that seeded human bone marrow mononuclear cells (BMCs) into the biodegradable scaffold secreted monocyte chemoattractant protein-1 (MCP-1), recruiting early host (SCID/bg mouse) monocytes and subsequently the scaffold transformed into functional blood vessels[28]

Summary

Introduction

Vascular grafts are needed for many clinical conditions such as coronary artery disease, end-stage renal disease, and peripheral artery occlusion disease. While adding polymer sheets or meshes could achieve a 100% yield rate[18], the tubular tissue is not completely autologous This method had been applied to the autologous transplantation of organs such as the bladder, uterus, and vas deferens (use polyethylene balls and boiled blood clots as molds)[19], as well as urethral grafts (use silicone tubes as molds)[17], and yielded favorable outcomes. The yield rates were not detailed in the reports, and the reported durations that were needed to produce useful grafts in mouse models ranged from 2 to 8 weeks[16,17,18,20] This limitation might add uncertainty to its further application. We hereby conducted a study to determine the mechanical properties, patency rate, ECM expression, and smooth muscle differentiation of the vascular grafts produced through this method

Methods

Results

Discussion

Conclusion