Engineering Particle-based Materials for Vasculogenesis

Vascular networks are critical to the survival of cells within materials designed for regenerative medicine. Developing approaches to vascularize three-dimensional (3D) in vitro models that recreate tissue physiology and 3D tissue constructs for regenerative medicine remain an important focus of tissue engineering. Granular hydrogels are emerging as a promising class of materials for the regeneration of damaged tissues and fabricating tissue constructs. While granular hydrogels have supported vasculature formed by angiogenesis and fabrication processes that establish channels, parameters for designing these materials to support formation of vasculature by vasculogenesis from cells contained within these materials are not fully understood and remain largely unexplored. In this study, vasculogenesis within 3D granular hydrogels formed from polyethylene glycol (PEG) microgels are studied for its potential to establish a microvascular network within this class of materials. Self-organization of endothelial cells into networks within hours is observed in the presence of fibroblasts, and the effects of cell adhesive ligands (RGD) and porosity are measured. Increasing porosity is observed to enhance vasculogenesis while the addition of RGD impairs microvessel network formation. This work establishes parameters that support robust microvasculature formation within granular hydrogels that might be broadly applicable to this class of materials, with implications for other morphogenetic processes in 3D systems.