title: Directed endothelial cell morphogenesis in micropatterned gelatin methacrylate hydrogels.
abstract: Engineering of organized vasculature is a crucial step in the development of functional and clinically relevant tissue constructs. A number of previous techniques have been proposed to spatially regulate the distribution of angiogenic biomolecules and vascular cells within biomaterial matrices to promote vascularization. Most of these approaches have been limited to two-dimensional (2D) micropatterned features or have resulted in formation of random vasculature within three-dimensional (3D) microenvironments. In this study, we investigate 3D endothelial cord formation within micropatterned gelatin methacrylate (GelMA) hydrogels with varying geometrical features (50-150 μm height). We demonstrated the significant dependence of endothelial cells proliferation, alignment and cord formation on geometrical dimensions of the patterned features. The cells were able to align and organize within the micropatterned constructs and assemble to form cord structures with organized actin fibers and circular/elliptical cross-sections. The inner layer of the cord structure was filled with gel showing that the micropatterned hydrogel constructs guided the assembly of endothelial cells into cord structures. Notably, the endothelial cords were retained within the hydrogel microconstructs for all geometries after two weeks of culture; however, only the 100 μm-high constructs provided the optimal microenvironment for the formation of circular and stable cord structures. Our findings suggest that endothelial cord formation is a preceding step to tubulogenesis and the proposed system can be used to develop organized vasculature for engineered tissue constructs.
authors.affiliation: Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nikkhah
authors.forename: Nouran
authors.initials: N
authors.lastname: Eshak
authors.forename: Pinar
authors.initials: P
authors.lastname: Zorlutuna
authors.forename: Nasim
authors.initials: N
authors.lastname: Annabi
authors.forename: Marco
authors.initials: M
authors.lastname: Castello
authors.forename: Keekyoung
authors.initials: K
authors.lastname: Kim
authors.forename: Alireza
authors.initials: A
authors.lastname: Dolatshahi-Pirouz
authors.forename: Faramarz
authors.initials: F
authors.lastname: Edalat
authors.forename: Hojae
authors.initials: H
authors.lastname: Bae
authors.forename: Yunzhi
authors.initials: Y
authors.lastname: Yang
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D049109:Cell Proliferation; D002470:Cell Survival; D042783:Endothelial Cells / Q000166:cytology*; D005780:Gelatin / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008689:Methacrylates / Q000737:chemistry*; D018613:Microscopy, Confocal; D055616:Microtechnology; D009024:Morphogenesis; D013499:Surface Properties; D023822:Tissue Engineering / Q000379:methods
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D008689:Methacrylates; D005780:Gelatin