Synthesis of photocrosslinkable hydrogels for engineering three-dimensional vascular-like constructs by surface tension-driven assembly

摘要

Surface tension-driven assembly is a simple routine used in modular tissue engineering to create three-dimensional (3D) biomimetic tissues with desired structural and biological characteristics. A major bottleneck for this technology is the lack of suitable hydrogel materials to meet the requirements of the assembly process and tissue regeneration. Identifying specific requirements and synthesizing novel hydrogels will provide a versatile platform for generating additional biomimetic functional tissues using this approach. In this paper, we present a novel composite hydrogel system based on methacrylated gelatin and gamma-polyglutamic acid by UV copolymerization as the building block for fabricating vascular-like tissue via surface tension-driven assembly. The resulting composite hydrogels exhibited the improved mechanical properties and hydrophilicity, which greatly facilitate the assembly process. Subsequent cell encapsulation experiment proved that the hydrogel could provide 3D support for cellular spreading and migration. Furthermore, based on the composite microgel building blocks, cylindrical vascular-like construct with a perfusable microchannel was generated by the needle-assisted sequential assembly. In order to construct a biomimetic vascular tissue, the endothelial cells and smooth muscle cells were encapsulated in the microgels assembly with a spatial arrangement to build a heterogeneous double layer tubular structure and the cells could readily elongate and migrate in the hollow concentric construct over 3 days. These data suggest that this composite hydrogel is an attractive candidate for surface tension-driven assembly purposes, making the hydrogel potentially applicable in the fabrication of biomimetic vascularized tissues.