Micro blood vessels and tissue ducts
Inventors
Adams, André A. • Daniele, Michael • Ligler, Frances S.
Assignees
Publication Number
US-10208289-B2
Publication Date
2019-02-19
Expiration Date
2026-06-09
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Abstract
A fiber includes one or more layers of polymer surrounding a central lumen, and living animal cells disposed within the lumen and/or within at least one of the one or more layers, wherein the fiber has an outer diameter of between 5 and 8000 microns and wherein each individual layer of polymer has a thickness of between 0.1 and 250 microns. Also disclosed are model tissues including such fibers, and method of making such fibers. The fibers can serve as synthetic blood vessels, ducts, or nerves.
Core Innovation
The invention provides a fiber comprising one or more layers of polymer surrounding a central lumen, with living mammalian cells disposed within the lumen and/or within at least one of the polymer layers. The fiber has an outer diameter between 5 and 8000 microns and polymer layers each with thickness between 0.1 and 250 microns. The fiber is generated via a sheath flow method, where a core stream is concentrically surrounded by sheath streams in a microfluidic channel and polymerization of the polymerizable material forms the fiber. Multiple layers and complex shapes can be made by controlling the flows and channel structures.
The problem being addressed is the difficulty in producing physiologically appropriate engineered blood vessels, tissue ducts, nerves, and similar tubular structures suitable for tissue engineering and tissue-on-chip models. Prior techniques often produce cell cultures on planar substrates or channels that limit 3D tissue formation, involve complex manufacturing, or do not allow formation of free-standing, flexible, biocompatible tubular structures with living cells incorporated. There is a need for methods producing micro-scale vascularized tissues and ducts with multilayered architectures including cells arranged spatially as in natural tissues.
Claims Coverage
The claims include two independent claims directed to model tissues comprising fibers and methods of their construction, featuring living animal cells arranged in polymer layers and lumens formed by sheath flow and polymerization. The main inventive features correspond to the composition, structure, cellular disposition, and functional configuration of the fibers within model tissues.
Fiber with polymer layers and hollow lumen containing living cells
A fiber comprising one or more layers of polymer surrounding a hollow central lumen with an inner polymer surface nearest the lumen; living animal cells disposed in the model tissue including at least endothelial cells adhered to the inner polymer surface and optionally a second cell type within polymer layers or hydrogel scaffold; fiber having an outer diameter between 5 and 8000 microns and layer thickness between 0.1 and 250 microns; fiber remains intact during fluid flow serving as a physiological model of a blood vessel; and the fiber is surrounded by a hydrogel three-dimensional scaffold with inlet and outlet ports directing fluid through the lumen.
Model tissue with fibers having multiple concentric polymer layers and distinct cell types
A model tissue comprising a fiber with at least two concentric polymer layers surrounding a central lumen; living animal cells comprising at least endothelial cells adhered to the inner polymer surface and optionally in the lumen; at least two different animal cells disposed in different polymer layers or lumen; inlet and outlet ports operable to direct fluid through the lumen; fiber dimensions as above; fiber at least partially surrounded by a hydrogel matrix serving as three-dimensional scaffold distinct from outer polymer layer.
The independent claims cover model tissues incorporating fibers composed of polymer layers surrounding a central lumen, with living animal cells arranged in defined spatial configurations including endothelial cells lining the lumen and other cell types in polymer layers or scaffold. The fibers function as physiological models of blood vessels, tissue ducts, or nerves, having specified geometries and being integrated with fluidic ports and hydrogels. The inventive features emphasize the multilayered polymer fibrous architecture with living cells, luminal fluid flow, and biomimetic tissue constructs.
Stated Advantages
Capability to create fibers with physiologically relevant dimensions and multilayered architecture mimicking natural blood vessels, ducts, or nerves.
Ability to incorporate living animal cells within lumen and polymer layers preserving cell viability during polymerization.
Facilitation of three-dimensional tissue culture with biomimetic nutrient delivery through hollow lumens.
Modular and continuous manufacturing via hydrodynamic focusing enabling variable fiber shapes, sizes, and multi-component compositions.
Integration of engineered microvascular networks into tissue-on-chip systems for improved modeling of biological processes including vascularized bone formation.
Documented Applications
Model tissues comprising micro-blood vessels for studying vascular biology, tissue engineering, and physiological processes such as intramembranous ossification.
Tissue-on-chip systems incorporating free-standing vasculature with three-dimensional hydrogel scaffolds for culturing osteogenic and other cell types.
Fabrication of engineered blood vessels, tissue ducts, and nerve conduits with concentric layers of living cells mimicking natural tissue structures.
Use as physiological models for blood flow and nutrient delivery in research and drug screening.
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