Cardiac tissue constructs and methods of fabrication thereof
First Claim
1. A microfabrication platform for forming a tissue construct, comprising:
- a microwell;
a ramped support structure provided within said microwell, said ramped support structure comprising an annular ramped surface and an upper platform, wherein said annular ramped surface extends upwardly from a base of said microwell to said upper platform; and
one or more retaining structures provided on said upper platform of said ramped support structure, wherein said one or more retaining structures are positioned to apply tension to a tissue construct within said microwell during formation of the tissue construct.
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Accused Products
Abstract
Methods and devices are provided for the formation of cardiac tissue constructs. In some embodiments, methods are provided for forming cardiac tissue constructs that including cardiomyocytes, non-myocytes, and extracellular matrix, and which exhibit properties associated with healthy cardiac tissue. In some embodiments, microfabrication platforms are provided to support the transmission of dynamic electromechanical forces, such that the cardiac microtissue constructs may be formed mimicking the basic microenvironment found in the heart. The microfabrication platform may include retaining features for stabilizing the position of the microtissue construct during its formation, and the microfabrication platform may include a ramped support configured to produce tissue constructs having a ring geometry. In some embodiments, the microfabrication platform may be configured to for the application of point electrical stimulation, and/or to amplify the transduction of force into a visible displacement.
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Citations
29 Claims
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1. A microfabrication platform for forming a tissue construct, comprising:
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a microwell; a ramped support structure provided within said microwell, said ramped support structure comprising an annular ramped surface and an upper platform, wherein said annular ramped surface extends upwardly from a base of said microwell to said upper platform; and one or more retaining structures provided on said upper platform of said ramped support structure, wherein said one or more retaining structures are positioned to apply tension to a tissue construct within said microwell during formation of the tissue construct. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 28, 29)
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22. A method of forming a tissue construct using a microfabrication platform;
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the microfabrication platform comprising; a microwell; a ramped support structure provided within the microwell, the ramped support structure comprising an annular ramped surface and an upper platform, wherein the annular ramped surface extends upwardly from a base of the microwell to the upper platform; and one or more retaining structures provided on the ramped support structure, wherein the one or more retaining structures are configured to apply tension to a tissue construct within the microwell during formation of the tissue construct; the method comprising; dispensing, into the microwell, a cell-containing pre-polymerized matrix that is configured to form the tissue construct according to a remodeling process, wherein the pre-polymerized matrix is dispensed into a region surrounding the ramped support structure without contacting the one or more retaining structures; and incubating the microwell for a time duration suitable for remodeling of the pre-polymerized matrix into the tissue construct, such that the tissue construct moves upwards along the ramped support structure during the remodeling process and is retrained in a ring geometry by the retaining structures. - View Dependent Claims (23, 24, 25, 26)
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27. A microfabrication platform for forming a tissue construct, comprising:
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a microwell; a support structure provided within said microwell, said support structure comprising an annular lateral surface and an upper platform, wherein said lateral surface extends upwardly and inwardly from a base of said microwell to said upper platform; and two or more retaining structures supported by said support structure, wherein said two or more retaining structures are configured to apply tension to a tissue construct within said microwell during formation of the tissue construct; wherein said lateral surface has a shape configured to raise the tissue construct from said well base while preventing tissue formation between said retaining structures during a tissue remodeling process.
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Specification