Synthetic microfluidic systems for wound healing and hemostasis
Inventors
Prabhakarpandian, Balabhaskar • Pant, Kapil
Assignees
Publication Number
US-9291614-B2
Publication Date
2016-03-22
Expiration Date
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Abstract
A method of assaying wound healing can include: growing cells on the matrix in the first flow channel; introducing an agent that removes the matrix from the junction; introducing a matrix material into the second flow channel so as to form the second matrix in the second flow channel and junction; and detecting cellular migration into the junction onto the second matrix. The agent that removes the matrix can include a biomolecule or chemical agent. The method can include removing cells in the matrix in the junction before introducing the matrix material into the second flow channel. A bioactive agent can be introduced into the junction to determine if it modulates cellular migration and/or clot formation into the intersection openings of tissue and vascular channels.
Core Innovation
Wounds and uncontrolled bleeding or hemorrhage remains the leading cause of preventable death following trauma, and current in vitro models for testing wound healing and hemostatic efficacy rely primarily on experiments performed in static environments and fail to reproduce both the injury characteristics and the variety of physiological and biological mechanisms involved in wound healing and stopping hemorrhage; therefore, there remains a need in the art for a better system and methodology for studying wound healing and hemostasis.
The present invention includes a device and methodology to study and characterize wound healing or hemostasis in idealized and physiologically realistic microenvironments, and the device and methodologies allow for the study and visualization in real time of wound healing or hemostasis and provide a platform for developing therapeutics for wound healing or hemostasis.
In one embodiment, a device can include a central channel having an inlet and an outlet; one or more outer channels adjacent to the central channel, each outer channel having an inlet and an outlet; a wall located between the central channel and one or more outer channels; at least one aperture between the central channel and one or more outer channels so as to fluidly couple the central channel and one or more outer channels; and a degradable matrix located in the at least one aperture so as to fluidly isolate the central channel and one or more outer channels from each other.
Claims Coverage
The independent claim (one independent claim identified) includes 10 main inventive features.
Central channel having an inlet and an outlet
The claim recites a central channel having an inlet and an outlet.
Outer channels adjacent to the central channel
The claim recites one or more outer channels adjacent to the central channel, each outer channel having an inlet and an outlet.
Wall located between channels
The claim recites a wall located between the central channel and one or more outer channels.
At least one aperture fluidly coupling channels
The claim recites at least one aperture in the wall between the central channel and one or more outer channels so as to fluidly couple the central channel and one or more outer channels.
Degradable matrix isolating the aperture
The claim recites a degradable matrix located in the at least one aperture so as to fluidly isolate the central channel and one or more outer channels from each other.
Endothelial cell culture in central channel
The claim recites culturing endothelial cells in the central channel [procedural detail omitted for safety].
Tissue cell culture in outer channels
The claim recites culturing tissue cells in the one or more outer channels [procedural detail omitted for safety].
Degradation of matrix to couple channels
The claim recites degrading the degradable matrix in the at least one aperture so as to fluidly couple the central channel and the one or more outer channels [procedural detail omitted for safety].
Flowing blood through the central channel
The claim recites flowing blood, whole or diluted, through the central channel [procedural detail omitted for safety].
Determination of hemostasis by aperture occlusion
The claim recites determining whether or not hemostasis occurs at the at least one aperture by determining whether or not the at least one aperture becomes occluded after the degradable matrix has been degraded from the at least one aperture, and, when the at least one aperture becomes occluded, hemostasis is determined to have occurred.
The independent claim covers a microfluidic device architecture with central and outer channels separated by a wall with apertures containing a degradable matrix, together with cell culture in the channels, controlled removal of the degradable matrix to open fluidic coupling, perfusion of blood through the central channel, and determination of hemostasis by occlusion of the aperture.
Stated Advantages
Allows study and characterization of wound healing and hemostasis in idealized and physiologically realistic microenvironments.
Enables study and visualization in real time of wound healing or hemostasis.
Provides a platform for developing, testing and screening hemostatic and anti-thrombotic drugs and wound healing therapeutics with data that translate to relevant in vivo conditions.
Reduces the need for animal experiments and reduces reagent/cell use via disposable chips and a flow- and morphologically realistic environment.
Documented Applications
Studying wound healing phenomena including creation of uniform, repeatable wounds and detecting cellular migration into wounded locations.
Assaying hemostasis and modeling hemorrhage, including creating bleeding wounds of varying sizes and monitoring clot formation and occlusion after induced injury.
Screening and testing hemostatic agents, hemostatic dressings, anti-thrombotic drugs, and drugs that promote wound healing in physiologically realistic flow conditions.
Modeling effects of altered mechanical and chemical environments, including dilution of coagulation factors, changes in pH and temperature, and other coagulopathy-relevant parameters.
Medium to high-throughput screening and real-time visualization for quantitative assessment of thrombotic potential and therapeutic efficacy.
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