Sacrificial Ice Templates for Engineering Freestanding Hierarchical Vascular Systems

Abstract

To ability to engineer a functional hierarchical vascular network is one of the most demanding and unaddressed challenges in tissue engineering and regenerative medicine. It is the various structural, mechanical, and biological properties of natural blood vessels that give rise to the hierarchically dimensioned architecture and range of localised functional requirements throughout the native vascular system. This has proven to be difficult to synthetically replicate and, so far, no material or method can conclusively meet the requirements of engineering a functional holistic vascular system. This dissertation presents a novel method of utilising ice as a unique and versatile material with the potential to address these challenges. This is demonstrated by using ice to create sacrificial templates, which could be cast or 3D printed into freestanding hierarchically branching vascular structures. These sacrificial ice templates could be coated with a diverse range of materials including tropoelastin, polycaprolactone, silk, polydimethylsiloxane, and combinations thereof. This facilitated the fabrication of freestanding vascular structures with hierarchical dimensions, varying localised functions, tuneable mechanical properties, luminal surfaces that supported the growth of vascular endothelial cells, and nutrient-permeable vessel walls. These engineered vessels were validated in vitro and in vivo for their application in vascular grafting and vascularising engineered synthetic tissues. This adaptable platform technology presents an elegant method of engineering synthetic vasculature that more closely mimics the native vascular system in both form and function. Through this study, these engineered vascular structures have demonstrated potential across wider applications in both tissue engineering and regenerative medicine.