Abstract: The present disclosure provides compositions, systems, and methods related to engineered vascular tissue models. In particular, the present disclosure provides compositions, systems, and methods pertaining to three-dimensional engineered vascular tissue models generated using vascular smooth muscle cells which emulate the structure and functionality of human vasculature.

Abstract: Described are methods for embedding one or more therapeutic agents into vascular grafts and other scaffold-based devices, and methods of implanting vascular grafts comprising tubular scaffolds into subjects. The tubular scaffolds comprise hydrogel nanofibers that have internally aligned polymer chains and may contain one or more therapeutic agents.

Abstract: The presently disclosed subject matter provides a scalable and electrostretching approach for generating hydrogel microfibers exhibiting uniaxial alignment from aqueous polymer solutions. Such hydrogel microfibers can be generated from a variety of water-soluble natural polymers or synthetic polymers. The hydrogel microfibers can be used for controlled release of bioactive agents. The internal uniaxial alignment exhibited by the presently disclosed hydrogel fibers provides improved mechanical properties to hydrogel microfibers, and contact guidance cues and induces alignment for cells seeded on or within the hydrogel microfibers.

Abstract: Described are methods of making vascular grafts from man-made tubular scaffolds, tubular scaffolds, and methods implanting vascular grafts comprising tubular scaffolds into subjects. The tubular scaffolds of the present invention are made of hydrogel nanofibers that have internally aligned polymer chains and may be cellularized.

Abstract: The present invention describes methods for quantifying and analyzing cell migration and drug screening. Such methods include a gel (or a hydrogel) comprising a polymer, and cells that forms an oxygen gradient within the gel by controlling the balance of the diffusion of oxygen through the top of the gel and by the consumption of oxygen uptake by the cells. The migration of the cells is determined while the cells are grown in the gel of the present invention.

Abstract: Low oxygen tension is a critical regulator of the developing or regenerating vasculature. The present invention is based on the determination that low oxygen tension during early stages of early vascular cell (EVC) derivation induces endothelial commitment and maturation of pluripotent stem cells. Inhibition of reactive oxygen species generation during the early stages of differentiation abrogates the endothelial inductive effects of the low oxygen environments. Methods of generating various types of cells from pluripotent stem cells (PSCs) are described, as well as compositions and methods of use thereof. In particular, generation of EVCs, bicellular vascular populations, early endothelial cells (ECs) and pericytes via culture in a low oxygen environment is described.

Abstract: Low oxygen tension is a critical regulator of the developing or regenerating vasculature. The present invention is based on the determination that low oxygen tension during early stages of early vascular cell (EVC) derivation induces endothelial commitment and maturation of pluripotent stem cells. Inhibition of reactive oxygen species generation during the early stages of differentiation abrogates the endothelial inductive effects of the low oxygen environments. Methods of generating various types of cells from pluripotent stem cells (PSCs) are described, as well as compositions and methods of use thereof. In particular, generation of EVCs, bicellular vascular populations, early endothelial cells (ECs) and pericytes via culture in a low oxygen environment is described.

Abstract: Early vascular cells (EVCs), including endothelial cells and pericytes, are generated from hiPSCs. Unlike the isolated endothelial progenitor cells, the differentiated ECs mature and are functional. When encapsulated in synthetic hydrogel, EVCs respond to matrix cues and self-assembled to form three-dimensional EVCs. Moreover, these EVCs respond to hypoxic microenvironment and undergo vasculogenesis to form complex 3D networks.

Abstract: The present invention relates to the area of in vitro cell populations useful for generating vascular networks in vitro and are suitable for use in vivo for regeneration of vascular tissue. In some embodiments, the bipotent cell population of the present invention comprise endothelial cells and pericytes that express vascular endothelial cadherin and are 95% or more positive for CD105 and CD146, and which work syergistically to recreate vascular tissues in vitro.

Abstract: Novel hydrogels that can serve as 3D hypoxic microenvironments are disclosed. Oxygen controllable, hypoxia-inducible hydrogels (HI hydrogels) are composed of a phenolic agent and polymer backbone, which can form hydrogel networks via oxygen consumption in an enzyme-mediated crosslinking reaction. The HI hydrogels are degradable, cytocompatible, and have tunable mechanical properties. Oxygen levels and gradients within the HI hydrogels are controlled and precisely predicted. As a result, the HI hydrogels induce prolonged hypoxic conditions. The HI hydrogels guide vascular morphogenesis in vitro by activating hypoxia-inducible factors and promote neovascularization from tissue, as well as stimulate tissue in dynamic in vivo environments. The HI hydrogels are a new class of biomaterials that are useful in many applications, ranging from the engineering of de novo tissues and disease models to the treatment of vascular disorders.

Abstract: Described are methods of making vascular grafts from man-made tubular scaffolds, tubular scaffolds, and methods implanting vascular grafts comprising tubular scaffolds into subjects. The tubular scaffolds of the present invention are made of hydrogel nanofibers that have internally aligned polymer chains and may be cellularized.

Abstract: Methods for promoting skin regeneration, promoting hair follicle regeneration, and reducing scarring by topically administering polysaccharide-based hydrogel compositions to injured skin are presented.

Abstract: The present invention describes methods for quantifying and analyzing cell migration and drug screening. Such methods include a gel (or a hydrogel) comprising a polymer, and cells that forms an oxygen gradient within the gel by controlling the balance of the diffusion of oxygen through the top of the gel and by the consumption of oxygen uptake by the cells. The migration of the cells is determined while the cells are grown in the gel of the present invention.

Abstract: The presently disclosed subject matter provides a scalable and electrostretching approach for generating hydrogel microfibers exhibiting uniaxial alignment from aqueous polymer solutions. Such hydrogel microfibers can be generated from a variety of water-soluble natural polymers or synthetic polymers. The hydrogel microfibers can be used for controlled release of bioactive agents. The internal uniaxial alignment exhibited by the presently disclosed hydrogel fibers provides improved mechanical properties to hydrogel microfibers, and contact guidance cues and induces alignment for cells seeded on or within the hydrogel microfibers.

Abstract: Slow vascularization of functional blood limits the transplantation of tissue constructs and the recovery of ischemic and wounded tissues. Blood vessel ingrowth into polysaccharide-based hydrogel scaffolds remains a challenge. A synergistic effect of multiple angiogenic GFs was established; the co-encapsulation of VEGF plus other growth factors induced more and larger blood vessels than any individual GF, while the combination of all GFs dramatically increased the size and number of newly formed functional vessels. Rapid, efficient, and functional neovascularization may be achieved.

Abstract: The present invention is in the area of pluripotent stem cells and more particularly deals with a method to differentiate a vascular network from stem cells.

Abstract: Early vascular cells (EVCs), including endothelial cells and pericytes, are generated from hiPSCs. Unlike the isolated endothelial progenitor cells, the differentiated ECs mature and are functional. When encapsulated in synthetic hydrogel, EVCs respond to matrix cues and self-assembled to form three-dimensional EVCs. Moreover, these EVCs respond to hypoxic microenvironment and undergo vasculogenesis to form complex 3D networks.

Abstract: This invention relates, e.g., to a method for differentiating mammalian (e.g., human) pluripotent stem cells (PSCs) into endothelial cells (ECs) in vitro, by plating a single-cell suspension of PSCs onto a suitable surface such as type IV collagen and culturing the cells with VEGF after which ECs can be harvested. A preferred embodiment of the method first cultures the cells without VEGF and then sequentially cultures the cells with VEGF. Differentiation can be enhanced by adding an inhibitor of transforming growth factor ? to the culturing with VEGF.

Abstract: Described are methods for differentiating mammalian pluripotent stem cells towards a population of cells that can self-organize into vascular networks in vitro when harvested cells of the present invention are embedded into a hydrophilic matrix such as a hydrogel.

Abstract: Novel hydrogels that can serve as 3D hypoxic microenvironments are disclosed. Oxygen controllable, hypoxia-inducible hydrogels (HI hydrogels) are composed of a phenolic agent and polymer backbone, which can form hydrogel networks via oxygen consumption in an enzyme-mediated crosslinking reaction. The HI hydrogels are degradable, cytocompatible, and have tunable mechanical properties. Oxygen levels and gradients within the HI hydrogels are controlled and precisely predicted. As a result, the HI hydrogels induce prolonged hypoxic conditions. The HI hydrogels guide vascular morphogenesis in vitro by activating hypoxia-inducible factors and promote neovascularization from tissue, as well as stimulate tissue in dynamic in vivo environments. The HI hydrogels are a new class of biomaterials that are useful in many applications, ranging from the engineering of de novo tissues and disease models to the treatment of vascular disorders.