Systems and methods for reperfusion injury
Inventors
Prabhakarpandian, Balabhaskar • Pant, Kapil • Roehm, Kevin Daniel • Bhatt, Ketan Harendrakumar
Assignees
Publication Number
US-11782051-B2
Publication Date
2023-10-10
Expiration Date
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Abstract
A method of creating a reperfusion injury can include: providing a cell culture device having an internal chamber with at least one port coupled to a perfusion modulating system capable of modulating perfusion in the internal chamber, wherein the internal chamber includes a cell culture; perfusing a fluid through the internal chamber with the perfusion modulating system, wherein the perfusion modulating system includes at least one pump; reducing fluid flow through the internal chamber; reperfusing fluid flow through the internal chamber; and creating a reperfusion injury in the cell culture by the reperfusion of the fluid flow through the internal chamber. The cell culture includes at least one type of tissue cell. The cell culture can include a tissue construct formed of hydrogel and/or extracellular matrix.
Core Innovation
A method of creating a reperfusion injury described in the abstract and summary uses a cell culture device having an internal chamber with at least one port coupled to a perfusion modulating system capable of modulating perfusion in the internal chamber, wherein the internal chamber includes a cell culture. The method includes perfusing a fluid through the internal chamber with the perfusion modulating system (wherein the perfusion modulating system includes at least one pump), reducing fluid flow through the internal chamber, reperfusing fluid flow through the internal chamber, and creating a reperfusion injury in the cell culture by the reperfusion of the fluid flow through the internal chamber.
The background states that ischemia and hypoxia occur in pathological conditions such as cancer, stroke, acute renal failure, and myocardial infarction, and that reperfusion can create a reperfusion injury involving reactive oxygen species, altered calcium handling, microvascular and endothelial dysfunction, altered cellular metabolism, and activation of neutrophils, platelets and complement. The patent frames the need for devices and methods that provide improved experimental analysis and studies on cells and cultures that experience reperfusion and reperfusion injury, noting limitations of in vivo animal models and of existing in vitro approaches.
Claims Coverage
The patent includes one independent method claim. The main inventive features extracted from that independent claim are listed below.
Method for creating a reperfusion injury in a cell culture device
Providing a cell culture device having an internal chamber with at least one port coupled to a perfusion modulating system capable of modulating perfusion in the internal chamber, wherein the internal chamber includes a cell culture; perfusing a fluid through the internal chamber with the perfusion modulating system (wherein the perfusion modulating system includes at least one pump); reducing fluid flow through the internal chamber; reperfusing the fluid flow through the internal chamber; and creating the reperfusion injury in the cell culture by reperfusing the fluid flow through the internal chamber.
The independent claim covers a procedure that couples a cell culture device to a perfusion modulating system with at least one pump to induce reduced flow and subsequent reperfusion in an internal chamber containing a cell culture, thereby creating a reperfusion injury.
Stated Advantages
Provides improved experimental analysis and studies on cells and cultures that experience reperfusion and reperfusion injury.
Enables a platform for studying myocardial ischemia and ischemia/hypoxia in a physiological microenvironment including synthetic microvascular networks (SMN) or idealized microvascular networks (IMN).
Amenable to medium to high throughput assays and integration with well plate formats for therapeutic screening.
Allows real-time visualization and monitoring, including use of electrodes (2D and 3D) for non-invasive electrical monitoring of cells.
Can reduce reliance on animal studies and provide a cost-effective tool for studying new therapeutic approaches.
Documented Applications
Modeling ischemia, hypoxia, and reperfusion injury on cultured cells by modulating perfusion in microfluidic devices.
Studying myocardial ischemia (MI) by simulating interruption and reperfusion of media/oxygen supply to myocytes in a physiological microenvironment.
Assaying cells from organs including brain, cardiac, kidney, liver and intestine to model ischemia reperfusion injury (IRI).
Developing and screening therapeutics and stem cell therapies for treating ischemia, hypoxia, and post-reperfusion injury using medium to high throughput assays.
Monitoring cellular responses before, during, and after ischemia and reperfusion using optical methods and electrodes to assess viability, pH/hypoxia, biomarkers, and electrical activity.
Characterizing biochemical and cellular mechanisms associated with IRI, including production or changes in reactive oxygen species, intracellular calcium, microvascular and endothelial dysfunction, activation of neutrophils, platelets and complement, eicosanoids, nitric oxide, endothelin, cytokines, proteases, and related biomarkers.
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