Tissue engineered cellular sheets, methods of making and use thereof
First Claim
1. A method of making a living stent, said method comprising:
- culturing a population of adherent cells, in a culture container in the presence of one or more tissue manipulation device(s) under conditions to allow the formation of a tissue sheet comprised of cells and extracellular matrix formed by the cells in contact with the one or more tissue manipulation device(s) whereby the one or more tissue manipulation device(s) anchors the tissue sheet in the culture container;
removing the tissue sheet from the culture container;
contacting a biocompatible tubular structure with the tissue sheet to form one or more layers of the tissue sheet in contact with the tubular structure thereby forming a living stent; and
removing one or more tissue manipulation device(s) prior to, during, or after contacting the tubular structure.
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0 Petitions
Accused Products
Abstract
The disclosure provides methods and composition to build living tissue covered stents and the like. These tissue coated stents provide a barrier against cell migration to the lumen of the vessel. Since the tissue can surround and envelope the stent, foreign body responses to the stent material are reduced and delayed. The tissue coating is also relatively impermeable to transmural flow, so the wrapped stent can act as a bypass vessel. The tissue is also robust enough to act as a stand alone vessel, without requiring the presence of the metallic stent. These stents can be endothelialized to reduce thrombosis. The genetic modifications described in this disclosure allow for functional organs to be built that express agents that are anti-restenotic or anti-thrombogenic. The use of tissue manipulation devices further allows for the assembly of complex tissue engineered organs. The tissue manipulation devices provide a method of anchoring the tissue sheets to the cell culture substrate to promote prolonged maturation and subsequent increased mechanical strength. The tissue manipulation devices also provide a technique to facilitate removal of the sheet from the culture container and subsequent production steps to assemble more complex three dimensional organs from the robust sheet. The tissue manipulation devices also facilitate automated handling of the sheets in the assembly processes.
38 Citations
31 Claims
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1. A method of making a living stent, said method comprising:
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culturing a population of adherent cells, in a culture container in the presence of one or more tissue manipulation device(s) under conditions to allow the formation of a tissue sheet comprised of cells and extracellular matrix formed by the cells in contact with the one or more tissue manipulation device(s) whereby the one or more tissue manipulation device(s) anchors the tissue sheet in the culture container; removing the tissue sheet from the culture container; contacting a biocompatible tubular structure with the tissue sheet to form one or more layers of the tissue sheet in contact with the tubular structure thereby forming a living stent; and removing one or more tissue manipulation device(s) prior to, during, or after contacting the tubular structure. - View Dependent Claims (5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 20, 23, 25)
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2. A method of making a living stent, said method comprising:
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culturing a population of adherent cells in a culture container in the presence of one or more tissue manipulation device(s) under conditions to allow the formation of a tissue sheet comprised of cells and extracellular matrix formed by the cells in contact with the one or more tissue manipulation device(s) whereby the one or more tissue manipulation device(s) anchors the tissue sheet in the culture container; removing the tissue sheet from the culture container; and contacting a biocompatible tubular structure with the tissue sheet to form one or more layers of the tissue sheet in contact with the tubular structure thereby forming a living stent; wherein the tubular structure is a biocompatible stent made of a biodegradable material.
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3. A method of making a living stent, said method comprising:
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culturing a population of adherent cells in a culture container in the presence of one or more tissue manipulation device(s) under conditions to allow the formation of a tissue sheet comprised of cells and extracellular matrix formed by the cells in contact with the one or more tissue manipulation device(s) whereby the one or more tissue manipulation device(s) anchors the tissue sheet in the culture container; removing the tissue sheet from the culture container; and contacting a biocompatible tubular structure with the tissue sheet to form one or more layers of the tissue sheet in contact with the tubular structure thereby forming a living stent; wherein the tubular structure is a biocompatible stent made of a non-biodegradable material.
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4. A method of making a living stent, said method comprising:
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culturing a population of adherent cells in a culture container in the presence of one or more tissue manipulation device(s) under conditions to allow the formation of a tissue sheet comprised of cells and extracellular matrix formed by the cells in contact with the one or more tissue manipulation device(s) whereby the one or more tissue manipulation device(s) anchors the tissue sheet in the culture container; removing the tissue sheet from the culture container; and contacting a biocompatible tubular structure with the tissue sheet to form one or more layers of the tissue sheet in contact with the tubular structure thereby forming a living stent wherein the tubular structure is a support mandrel. - View Dependent Claims (18, 19)
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21. A method of making a composition, said method comprising:
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a) preparing a tissue sheet cultured in vitro by culturing a population of adherent cells, in a culture container in the presence of one or more tissue manipulation device(s), wherein the population of adherent cells grow to form the tissue sheet whereby the tissue sheet is in contact with the one or more tissue manipulation device(s); and b) enveloping a biocompatible stent comprising a therapeutic agent with the tissue sheet. - View Dependent Claims (24, 26, 27, 28, 29, 30, 31)
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22. A method of making a composition, said method comprising:
forming a tissue sheet of cells into a tubular structure by rolling the tissue sheet upon itself one or more times, wherein the tissue sheet is produced from a population of adherent cells cultured in a culture container in the presence of one or more tissue manipulation device(s), wherein the population of adherent cells grow to form the tissue sheet anchored by the one or more tissue manipulation device(s).
Specification