US-12618042-B2 - System and method for creating tissue

US12618042B2US 12618042 B2US12618042 B2US 12618042B2US-12618042-B2

Abstract

A system and method for growing and maintaining biological material including producing a protein associated with the tissue, selecting cells associated with the tissue, expanding the cells, creating at least one tissue bio-ink including the expanded cells, printing the at least one tissue bio-ink in at least one tissue growth medium mixture, growing the tissue from the printed at least one tissue bio-ink, and maintaining viability of the tissue.

Inventors

Christopher C. Langenfeld
Richard J. Lanigan
Michael A. Baker
David Blumberg, Jr.
Richard E. Andrews
Derek G. Kane
Dane C. Fawkes
Thomas J. Bollenbach
Michael C. Tilley
Stuart A. Jacobson
John F. Mannisto
David D. B Cannan
Dirk A. Van der Merwe
Dean Kamen
Jason A. Demers
Frederick Morgan
Timothy D. Moreau
Brian D. Tracey
Matthew Ware

Assignees

DEKA PRODUCTS LIMITED PARTNERSHIP

Dates

Publication Date: 20260505
Application Date: 20240216

Claims (13)

1 . A tissue enclosure for the creation of tissue, comprising: a core including a cavity having a granular scaffolding therein, at least one material ingress and at least one material egress; an ingress filter assembly operably coupled to each of the at least one material ingress; an egress filter assembly operably coupled to each of the at least one material egress, said ingress and egress filter assemblies preventing tissue from migrating from said cavity; and at least one monitoring area operably coupled to said core to provide viewing of said cavity, wherein tissue is maintained at least by fluid flowing through the cavity between the at least one material ingress and the at least one material egress, wherein the tissue is monitored through the at least one monitoring area.
2 . The tissue enclosure as in claim 1 further comprising: at least one plenum operably coupled with at least one of said ingress and/or said egress filter assemblies, the at least one plenum enabling the application of pressure to the cavity.
3 . The tissue enclosure as in claim 1 further comprising: at least one heater maintaining the temperature of the cavity.
4 . The tissue enclosure as in claim 1 further comprising: at least one medium surrounding the tissue within the cavity.
5 . The tissue enclosure as in claim 4 , wherein the at least one medium is a gel.
6 . The tissue enclosure as in claim 1 , wherein a multi-dimensional printer prints the tissue into the cavity.
7 . The tissue enclosure as in claim 2 , each of the at least one ingress and egress filter assemblies further comprising: at least one filter; at least one filter support operably coupled with the at least one filter; and at least one filter frame operably coupling the at least one filter and the at least one filter support with the at least one plenum.
8 . The tissue enclosure as in claim 1 , further comprising: a tissue enclosure top removably enclosing the tissue within the core.
9 . The tissue enclosure as in claim 1 , wherein the at least one monitoring area is a transparent window.
10 . A tissue enclosure for the creation of tissue comprising: a core having an open cavity, at least one monitoring area and at least one opening into the cavity, the core accommodating at least one material ingress and at least one material egress, the core containing the tissue, a granular scaffolding supporting the tissue, media, and metabolism products from the tissue; an incoming chamber in fluidic communication with said cavity and admitting a first material, the incoming chamber emitting the first material in response to a differential pressure within the tissue enclosure; at least one first filtration zone operably positioned between the incoming chamber and the core, the at least one first filtration zone subjecting the first material to at least one filter having a first pore size; an effluent chamber in fluidic communication with said cavity; and at least one second filtration zone operably positioned between effluent chamber and the core, the at least one second filtration zone subjecting the first filtered material, the media, the tissue, and the metabolism products to at least one filter having a second pore size, wherein the tissue enters the cavity through the at least one opening, and wherein the tissue is confined within the cavity by the at least one first filtration zone and the at least one second filtration zone, and wherein the life of the tissue is maintained by the first material entering the cavity through the at least one material ingress and by the metabolism products exiting the cavity through the at least one material egress.
11 . The tissue enclosure as in claim 10 wherein the at least one opening enables printing of the tissue.
12 . The tissue enclosure as in claim 10 wherein the at least one monitoring area comprises: a transparent window disposed opposite the at least one opening.
13 . The tissue enclosure as in claim 10 further comprising: at least one mount button accommodating kinematic mounting of the tissue enclosure upon a tissue enclosure holder having corresponding mount wells.

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser. No. 17/465,153, filed Sep. 2, 2021; which is a divisional of U.S. patent application Ser. No. 15/805,790, filed Nov. 7, 2017;which claims the benefit of: U.S. Provisional App. 62/418,784, filed Nov. 7, 2016; andU.S. Provisional App. 62/534,984, filed Jul. 20, 2017, all of which are incorporated herein by reference in their entirety. BACKGROUND The present teachings relate generally to tissue engineering, and more specifically to systems and methods to enable tissue creation. The current approach to growing structures in a granular gel bioreactor is to supply a fluid or pneumatic pressure gradient on an upstream reservoir or plenum to encourage flow through the granular gel and any cells or structures suspended in the gel. The flowing material could include nutrients and could wash away waste products from the structures. It might be optimal if the structures could remain positionally static while the nutrients flow through them. However, depending on the granular gel concentration, pressure amplitudes used, and other factors, the structures may only remain positionally static at a pressure gradient too low to provide a feasible flow rate of material. If the movement of the structures is too high, the structures may compress to a point where the cellular viability or future functionality of the tissue is compromised. In 2016, approximately 119,000 people were on a waiting list for an organ transplant, and yet only 33,606 transplants occurred, an 8.5% increase over 2015. This disparity continues to grow. Tissue engineering and regenerative medicine seek to address this shortage by creating viable cells, tissues, and organs for transplantation in a controlled setting such as a bioreactor. These cells, tissues, and organs could potentially replace animal and human subjects for drug development and testing. In order to accomplish this goal, tissue engineering has turned to 3D tissue printing. Tissue printing uses living cells and other biological materials as bio-ink to produce a 3D structure. There are three categories of printing technologies used in this field: inkjet-based bioprinting, pressure-assisted bioprinting, and laser-assisted bioprinting. In order to maintain the viability of the printed tissue structure, a steady supply of nutrients must enter a bioreactor that can house the printed tissue while waste exits from it. The field of tissue engineering faces the challenge of monitoring tissue production, which is crucial to ensuring that cells are growing and differentiating properly while receiving the appropriate nutrients and signals. However, monitoring developing tissue presents a unique challenge: obtaining high resolution images of developing cells and tissue in a non-invasive manner. Creating human tissue can involve problems such as achieving the necessary precision in a timely way to create the tissue, and maintaining the viability of the tissue while it awaits use. Currently tissue engineering is primarily a manual and empirical process without a great deal of reproducibility or quality assurance. What is needed is a combination of state-of-the-art engineering solutions applied to the biological problems of creating and maintaining tissue. One such technology is three-dimensional printing that can be used to print living cells, scaffolds for living cells, and/or complete organs. However, three-dimensionally printing even simple living tissues can require substantial improvements over current three-dimensional printing technology. Further, what is needed is a repeatable process so that the results of tissue creation can be predictable. Therefore, what is needed is a complete, automated system for creating tissue and maintaining its viability. SUMMARY The method of the present teachings for growing tissue can include, but is not limited to including, producing a protein associated with the tissue, selecting cells associated with the tissue, expanding the cells, creating at least one tissue bio-ink including the expanded cells, printing the at least one tissue bio-ink in at least one tissue growth medium mixture, growing the tissue from the printed at least one tissue bio-ink, and maintaining viability of the tissue. The method can optionally include maintaining the tissue, and packaging the tissue for transport. Producing the protein can include forming a recombinant protein precursor based on viral vectors associated with the tissue and cell lines associated with the tissue, forming disassociated protein precursor cells based on subjecting the recombinant protein precursor to at least one disassociation reagent and stress, creating at least one protein bio-ink based on the disassociated protein precursor cells and a sterile gel, creating at least one printable protein bio-ink based on the at least one protein bio-ink and at least one protein support material, printing the