Micro blood vessels and tissue ducts
Inventors
Adams, André A. • Daniele, Michael • Ligler, Frances S.
Assignees
Publication Number
US-9926534-B2
Publication Date
2018-03-27
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 comprises a fiber including 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 ranging between 5 and 8000 microns and each individual polymer layer has a thickness between 0.1 and 250 microns. Such fibers are generated using a sheath flow technique, wherein a core stream is surrounded by one or more sheath streams, and polymerization of polymerizable materials contained in the streams forms the tubular fiber.
The fibers can mimic natural biological structures such as synthetic blood vessels, tissue ducts, or nerves, and can incorporate multiple layers containing different living animal cells. The fibers may be hollow or have a lumen filled with polymer, and their dimensions and structure can be controlled by the relative flow rates and shaping features in the microfluidic channel used in their manufacture. Cells can be added during fabrication in a biocompatible prepolymer or culture medium, allowing for cell encapsulation, adherence, or embedding within the fibers.
The problem being addressed stems from limitations in current tissue engineering and microfluidic technologies. Existing methods for engineering blood vessels commonly rely on cells grown within channels or seeded onto scaffolds, which do not produce free-standing vessels capable of branching or superfusion. Many existing models are planar and constrain tissue thickness due to limited nutrient transport, lacking physiologically appropriate, round, flexible, multi-cellular tubular structures. Prior fiber fabrication techniques often employ conditions incompatible with living cells, such as elevated temperature, high shear, or organic solvents. There is a need for precise fabrication of engineered blood vessels and ducts with physiologically appropriate shapes, dimensions, and properties, integrated into tissue-on-chip models, achieved via biocompatible manufacturing methods.
Claims Coverage
The patent includes two independent claims focused on methods of generating tubular fibers with living animal cells incorporated, employing specific channel structures and sheath flow techniques.
Use of fluid transporting structures on opposing channel surfaces to create sheath flow
A method wherein a channel has fluid transporting structures across its top and bottom surfaces, located facing one another, to generate a sheath flow comprising a core stream surrounded by sheath stream(s). These structures control the positioning and shape of the core within the channel.
Fabrication of tubular fibers containing living animal cells within the lumen and/or layers
The method involves introducing polymerizable material and living animal cells in core or sheath streams, forming one or more polymer layers surrounding a central lumen, with the cells disposed within the lumen or polymer layers, resulting in fibers with an outer diameter of 5 to 8000 microns and polymer layer thicknesses of 0.1 to 250 microns, polymerized to form tubular fibers.
Production of multilayer tubular fibers with differential cell placement
A method creating fibers with two or more concentric sheath streams surrounding the core, each potentially containing different living animal cells in different layers or lumen, allowing the fiber to have spatially distinct cellular arrangements, suitable for structures like blood vessels, ducts, or nerves.
The independent claims cover methods of producing multilayer, tubular polymer fibers incorporating living animal cells within the fibers' lumen and/or layers, using microfluidic channels with fluid transporting structures on opposing surfaces to control sheath flow and fiber geometry, with sizes and compositions tailored to mimic biological vessels and ducts.
Stated Advantages
Provides biocompatible methods for producing shaped polymer fibers containing living cells under mild conditions compatible with cell viability.
Enables production of free-standing, multi-layered tubular fibers mimicking natural blood vessels, ducts, or nerves with physiologically appropriate shapes, sizes, and flexibility.
Allows incorporation of multiple cell types in distinct layers or lumen, supporting complex tissue architectures and modeling.
Facilitates continuous, controlled fabrication of fibers with variable dimensions and shapes using microfluidic sheath flow with amenability to scale up.
Supports integration of engineered blood vessels into tissue-on-chip models, enhancing nutrient delivery and physiological relevance of in vitro tissue models.
Documented Applications
Synthetic blood vessels for tissue engineering and vascularized tissue-on-chip models.
Tissue ducts serving as conduits for fluid transfer in physiological studies.
Nerve scaffolds for directed nerve growth and neuroregenerative tissue engineering.
Biosensing and biomanufacturing using fibers encapsulating living bacterial cells or spores for continuous monitoring or bioremediation.
Encapsulation of enzymes or biological molecules within fibers for catalysis, sensing, or therapeutic delivery.
Liquid waveguides for optical measurements in microfluidics.
Flow cytometry devices using sheath flow for particle focusing.
Fabrication of specialty polymeric filaments and fibers with controlled geometry and gradients for biomedical and materials applications.
Modeling bone development and healing with vascularized tissue bioreactors incorporating the fibers as micro-blood vessels.
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