Microfabricated blood vessels undergo neoangiogenesis

• Published in: Biomaterials 2017-09, Vol.138, p.142-152
• Main Authors: DiVito, Kyle A, Daniele, Michael A, Roberts, Steven A, Ligler, Frances S, Adams, André A
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Anastomoses; Angiogenesis; Blood vessel; Capillaries - chemistry; Coculture Techniques; Dentistry; Endothelial Cells - cytology; Endothelial Cells - metabolism; Extracellular Matrix Proteins - metabolism; Feeder Cells; Fibroblasts - cytology; Fibroblasts - metabolism; Gelatin - chemistry; Humans; Hydrogels - chemistry; Microfluidics - methods; Microtechnology - methods; Microvessels - growth & development; Microvessels - ultrastructure; Neovascularization, Physiologic; Perfusion; Pericytes - cytology; Pericytes - metabolism; Polyhydroxyethyl Methacrylate - chemistry; Primary Cell Culture; Sheath-flow microfluidics; Tissue Engineering - methods; Umbilical Veins - cytology
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2017.05.012

Abstract The greatest ambition and promise of tissue engineering is to manufacture human organs. Before “made-to-measure” tissues can become a reality [1–3] , however, three-dimensional tissues must be reconstructed and characterized. The current inability to manufacture operational vasculature has limited the growth of engineered tissues. Here, free-standing, small diameter blood vessels with organized cell layers that recapitulate normal biological functionality are fabricated using microfluidic technology. Over time in culture, the endothelial cells form a monolayer on the luminal wall and remodel the scaffold with human extracellular matrix proteins. After integration into three-dimensional gels containing fibroblasts, the microvessels sprout and generate extended hollow branches that anastomose with neighboring capillaries to form a network. Both the microfabricated vessels and the extended sprouts support perfusion of fluids and particles. The ability to create cellularized microvessels that can be designed with a diameter of choice, produced by the meter, and undergo angiogenesis and anastomoses will be an extremely valuable tool for vascularization of engineered tissues. To summarize, ultraviolet (UV) photo-crosslinkable poly(ethylene glycol) and gelatin methacrylate polymers used in combination with sheath-flow microfluidics allow for the fabrication of small diameter blood vessels which undergo neoangiogenesis as well as other developmental processes associated with normal human blood vessel maturation. Once mature, these vessels can be embedded; perfused; cryogenically stored and respond to stimuli such as chemokines and shear stresses to mimic native human blood vessels. The applications range from tissue-on-chip systems for drug screening, characterization of normal and pathologic processes, and creation and characterization of engineered tissues for organ repair.