title: Geometric control of vascular networks to enhance engineered tissue integration and function.
abstract: Tissue vascularization and integration with host circulation remains a key barrier to the translation of engineered tissues into clinically relevant therapies. Here, we used a microtissue molding approach to demonstrate that constructs containing highly aligned "cords" of endothelial cells triggered the formation of new capillaries along the length of the patterned cords. These vessels became perfused with host blood as early as 3 d post implantation and became progressively more mature through 28 d. Immunohistochemical analysis showed that the neovessels were composed of human and mouse endothelial cells and exhibited a mature phenotype, as indicated by the presence of alpha-smooth muscle actin-positive pericytes. Implantation of cords with a prescribed geometry demonstrated that they provided a template that defined the neovascular architecture in vivo. To explore the utility of this geometric control, we implanted primary rat and human hepatocyte constructs containing randomly organized endothelial networks vs. ordered cords. We found substantially enhanced hepatic survival and function in the constructs containing ordered cords following transplantation in mice. These findings demonstrate the importance of multicellular architecture in tissue integration and function, and our approach provides a unique strategy to engineer vascular architecture.
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jan D
authors.initials: JD
authors.lastname: Baranski
authors.forename: Ritika R
authors.initials: RR
authors.lastname: Chaturvedi
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Stevens
authors.forename: Jeroen
authors.initials: J
authors.lastname: Eyckmans
authors.forename: Brian
authors.initials: B
authors.lastname: Carvalho
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Solorzano
authors.forename: Michael T
authors.initials: MT
authors.lastname: Yang
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Miller
authors.forename: Sangeeta N
authors.initials: SN
authors.lastname: Bhatia
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000737:chemistry; D000818:Animals; D001706:Biopsy; D003094:Collagen / Q000737:chemistry; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008809:Mice, Inbred C3H; D009130:Muscle, Smooth / Q000378:metabolism; D018919:Neovascularization, Physiologic; D051381:Rats; D012038:Regeneration; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000199:Actins; D003094:Collagen
keywords: angiogenesis; liver; regenerative medicine; tissue engineering; vascular biology