Journal
BIOMATERIALS
Volume 280, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.121286
Keywords
Tissue engineering; Graft perfusion; Multi-scale vasculature; Tissue vascularization; Tissue engineered blood vessels
Funding
- European Research Council (ERC) under the European Union [818808]
- United States-Israel Binational Science Foundation (BSF) [2017239]
- European Research Council (ERC) [818808] Funding Source: European Research Council (ERC)
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By combining living cells, biological hydrogel, and biodegradable synthetic polymer, a multi-scale vascular network within thick, implantable engineered tissues was successfully fabricated in this study. The functionality and patency of the multi-scale vascular network were demonstrated by dextran passage and physiological flow conditions, leading to significant improvements in blood perfusion compared to control micro-scale-vascularized grafts. This innovative approach of designing and fabricating multi-scale vascular architectures within 3D engineered tissues shows promise for both in vitro models and therapeutic translation research.
A functional multi-scale vascular network can promote 3D engineered tissue growth and improve transplantation outcome. In this work, by using a combination of living cells, biological hydrogel, and biodegradable synthetic polymer we fabricated a biocompatible, multi-scale vascular network (MSVT) within thick, implantable engineered tissues. Using a templating technique, macro-vessels were patterned in a 3D biodegradable polymeric scaffold seeded with endothelial and support cells within a collagen gel. The lumen of the macro-vessel was lined with endothelial cells, which further sprouted and anastomosed with the surrounding self-assembled capillaries. Anastomoses between the two-scaled vascular systems displayed tightly bonded cell junctions, as indicated by vascular endothelial cadherin expression. Moreover, MSVT functionality and patency were demonstrated by dextran passage through the interconnected multi-scale vasculature. Additionally, physiological flow conditions were applied with home-designed flow bioreactors, to achieve a MSVT with a natural endothelium structure. Finally, implantation of a multi-scale-vascularized graft in a mouse model resulted in extensive host vessel penetration into the graft and a significant increase in blood perfusion via the engineered vessels compared to control micro-scale-vascularized graft. Designing and fabricating such multi-scale vascular architectures within 3D engineered tissues may benefit both in vitro models and therapeutic translation research.
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