Bioartificial lung

• US 9,005,885 B2
• Filed: 06/04/2010
• Issued: 04/14/2015
• Est. Priority Date: 06/04/2009
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Ott, Harald C.
• Primary Examiner(s): Lankford, Blaine
• Assistant Examiner(s): BERKE-SCHLESSEL, DAVID W
• Application Number:
  US13/375,260
• Publication Number:
  US 20120141439A1
• Time in Patent Office: 1,775 Days
• Field of Search: None
• US Class Current: 435/1.2
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/3891 as distinct cell layers
• CPC Class Codes: A61M 16/0054 Liquid ventilation
• CPC Class Codes: A61M 2210/1039 Lungs
• CPC Class Codes: C12M 21/08 for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00
• CPC Class Codes: C12M 25/14 Scaffolds; Matrices in general C12N5/0068
• CPC Class Codes: C12M 29/10 Perfusion
• CPC Class Codes: C12M 33/00 Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus chemical or physical laboratory apparatus in general B01L, devices for taking cell samples A61B10/0045, withdrawing or distributing predetermined quantities of fluid B01L99/00
• CPC Class Codes: C12M 33/04 by injection or suction, e.g. using pipettes, syringes, needles pipettes in general B01L3/02
• CPC Class Codes: C12M 41/30 of concentration

Abstract

Presented is an airway organ bioreactor apparatus, and methods of use thereof, as well as bioartificial airway organs produced using the methods, and methods of treating subjects using the bioartificial airway organs.

Claims

1. A method of providing a fuctional bioartificial airway organ, the method comprising:

providing a decellularized lung tissue matrix comprising airway and vascular architecture;

seeding a lumen of the vascular architecture by perfusing endothelial cells through the vascular architecture;

seeding the lung tissue matrix with epithelial cells over the airway architecture through a wet ventilation line;

providing the lung tissue matrix with wet ventilation, through the airway architecture, and perfusion, through the vascular architecture, for a time sufficient to produce a wet-matured organ; and

providing the wet-matured organ with dry ventilation through the airway architecture, and with perfusion through the vascular architecture, for a time sufficient for providing a functional bioartifical lung that allows for the exchange of oxygen.

2. The method of claim 1, wherein the epithelial cells are human alveolar basal epithelial cells.

3. The method of claim 1, wherein

the endothelial cells are suspended in a fluid at a concentration of about 100 million cells per 10 cc of fluid;

and

the epithelial cells are suspended in a fluid at a concentration of about 100 million cells per 5 cc of fluid.

4. The method of claim 1, further comprising

monitoring the lung tissue matrix until the time sufficient to produce a wet-matured organ has passed;

stopping the wet ventilation to the wet-matured organ;

applying an artificial surfactant to the wet-matured organ; and

starting the dry ventilation to the wet-matured organ.

5. The method of claim 1, wherein providing the lung tissue matrix with wet ventilation comprises:

connecting the airway architecture to a wet ventilator via a wet ventilator line;

connecting the lung tissue matrix to a compliance chamber via a wet ventilation line;

increasing a wet airway pressure over the wet ventilation line; and

providing a wet positive and expiratory pressure (wPEEP) to the lung tissue matrix by elevating the compliance chamber.

6. The method of claim 5, wherein the wet ventilation is provided at a physiologic tidal volume.

7. The method of claim 1, wherein providing the wet-matured organ with dry ventilation comprises:

connecting the airway architecture to a dry ventilation chamber via a dry ventilation line;

connecting the dry ventilation chamber to a first dry ventilator over a dry positive and expiratory pressure (dPEEP) line;

increasing a dry airway pressure over the dry ventilation line;

disconnecting the wet ventilation line; and

connecting the wet-matured organ to a second dry ventilator via a dry ventilator line.

8. The method of claim 1, wherein the lung tissue matrix comprises decellularized human lung tissue or an artificial lung matrix.

9. The method of claim 1, wherein the bioartificial lung comprises a sufficient number of cells to provide full lung function or a fraction thereof.