title: Engineering of in vitro 3D capillary beds by self-directed angiogenic sprouting.
abstract: In recent years, microfluidic systems have been used to study fundamental aspects of angiogenesis through the patterning of single-layered, linear or geometric vascular channels. In vivo, however, capillaries exist in complex, three-dimensional (3D) networks, and angiogenic sprouting occurs with a degree of unpredictability in all x,y,z planes. The ability to generate capillary beds in vitro that can support thick, biological tissues remains a key challenge to the regeneration of vital organs. Here, we report the engineering of 3D capillary beds in an in vitro microfluidic platform that is comprised of a biocompatible collagen I gel supported by a mechanical framework of alginate beads. The engineered vessels have patent lumens, form robust ~1.5 mm capillary networks across the devices, and support the perfusion of 1 µm fluorescent beads through them. In addition, the alginate beads offer a modular method to encapsulate and co-culture cells that either promote angiogenesis or require perfusion for cell viability in engineered tissue constructs. This laboratory-constructed vascular supply may be clinically significant for the engineering of capillary beds and higher order biological tissues in a scalable and modular manner.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Juliana M
authors.initials: JM
authors.lastname: Chan
authors.forename: Ioannis K
authors.initials: IK
authors.lastname: Zervantonakis
authors.forename: Tharathorn
authors.initials: T
authors.lastname: Rimchala
authors.forename: William J
authors.initials: WJ
authors.lastname: Polacheck
authors.forename: Jordan
authors.initials: J
authors.lastname: Whisler
authors.forename: Roger D
authors.initials: RD
authors.lastname: Kamm
mesh_terms: D000464:Alginates; D002196:Capillaries / Q000254:growth & development*; D002478:Cells, Cultured; D018920:Coculture Techniques; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D007150:Immunohistochemistry; D044085:Microfluidics; D018919:Neovascularization, Physiologic; D054457:Tissue Scaffolds
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020723:Glucuronic Acid