Cross-circulation platform for recovery, regeneration, and maintenance of extracorporeal organs

Patent metadata

Field	Value
Publication number	US-12446572-B2
Application number	US-202418615506-A
Country	US
Kind code	B2
Filing date	Mar 25, 2024
Priority date	Jul 13, 2016
Publication date	Oct 21, 2025
Grant date	Oct 21, 2025

Abstract

Described are systems, methods, and devices relating to normothermic extracorporeal support of an organ, tissue, or bioengineered graft comprising cross-circulation (XC) perfusion for prolonged periods (days to weeks) via an XC perfusion circuit in connection with an extracorporeal host (e.g., animal, patient, organ transplant recipient) are disclosed. The XC perfusion circuit comprises auto-regulation of blood flow based on the trans-organ blood pressure difference between arterial and venous pressure. Recipient support enabled 36 h of normothermic perfusion that maintained healthy lungs with no significant changes in physiologic parameters and allowed for the recovery of injured lungs. Extended support enabled multiscale therapeutic interventions in all extracorporeal lungs. Lungs exceeded transplantation criteria.

First claim

What is claimed is:

1. A system for physiologic regulation of an extracorporeal organ, tissue or bioengineered graft via cross-circulation with a host organism, comprising
an extracorporeal organ chamber for containing and supporting the extracorporeal organ, tissue or bioengineered graft, wherein the chamber comprises a time- and temperature-controlled humidifier that directs a misting spray onto the organ, tissue or bioengineered graft and into the chamber to maintain a humid environment within the chamber; and
an extracorporeal cross-circulation circuit for connecting the extracorporeal organ, tissue or bioengineered graft with a host organism for cross-circulation of blood or plasma, which circuit comprises:
fluid conduits providing flow of the blood or plasma between a vascular system of the host organism to vasculature of the extracorporeal organ, tissue or bioengineered graft;
wherein a first fluid conduit for connecting the host organism to the extracorporeal organ comprises thereon a circulating pump which pumps blood through a circuit which splits to return blood cells directly back to a blood vessel of the host organism and plasma to the extracorporeal organ, and wherein the first fluid conduit comprises an oxygenator.

2. The system of claim 1 , wherein the oxygenator is downstream from the pump.

3. The system of claim 1 , which comprises one or more of
an arterial pressure sensor for sensing extracorporeal in-flow line pressure;
a venous pressure sensor for sensing extracorporeal out-flow line pressure.

4. The system of claim 3 , wherein the circulating pump regulates blood or plasma flow within a predetermined percentage range based on the trans-organ pressure difference between arterial and venous pressure measured by an arterial pressure sensor and venous pressure sensor.

5. The system of claim 1 , wherein one or more fluid conduits further comprise a flow probe, a sample port and/or a temperature probe.

6. The system of claim 1 , further comprising a heating element associated with at least one of the fluid conduits.

7. The system of claim 1 , further comprising the extracorporeal organ in place in the chamber and connected to the extracorporeal cross-circulation circuit.

8. The system of claim 7 , wherein the extracorporeal organ is a liver or lung.

9. The system of claim 8 , wherein the extracorporeal organ is a liver and the first fluid conduit comprises an oxygenator.

10. The system of claim 1 , wherein the extracorporeal organ chamber comprises
an organ-specific organ-negative molded soft bladder for supporting the organ, tissue or graft, and/or
a liquid-circulating loop in the interior of the soft bladder for recirculating liquid from a temperature-controlled reservoir by a pump to provide a temperature-controlled interior of the bladder maintained with recirculating temperature-controlled liquid in a range from 4° C. to 40° C.

11. The system of claim 1 , wherein the chamber further comprises one or more of the following features: integrated scale for monitoring and recording organ weight, real-time macroscopic video recording of the organ with remote monitoring capability, access ports with sterile air filter for biopsies and/or imaging, access for sterile manual interventions in chamber, and sterilizable and single-use disposable components.

12. The system of claim 1 , wherein the extracorporeal cross-circulation circuit further comprises one or more of the following features: a re-circulation tubing jacket for warming exposed tubing, integrated heat exchanger, integrated access ports for blood sampling, and remote monitoring and control of the circulating pump.

13. The system of claim 1 , which maintains the extracorporeal organ, tissue, or bioengineered graft in the chamber within a temperature range of from 30° C. to 40° C.

14. The system of claim 1 , wherein the circulating pump maintains a trans-organ blood pressure difference of between about 5-15 mm Hg.

15. The system of claim 1 , wherein the extracorporeal cross-circulation circuit cross-circulates plasma and further comprises at least one of the following:
a filter (PF) configured to permit return of blood cells directly to the host organism and perfusion of plasma through the organ, tissue or bioengineered graft; and
a leukocyte reduction filter (L) configured to prevent immunologic cells exiting the organ, tissue or bioengineered graft from entering the vascular system of the host organism.

16. The system of claim 1 , further comprising an extracorporeal organ chamber stand comprising
automatic height adjustability based on feedback from extracorporeal organ in-flow and out-flow line pressures; wherein the organ chamber stand includes the ability to raise and lower the organ chamber to modulate cross-circulation circuit pressures so that desirable perfusion rates are maintained;
at least one organ-specific accessory; and
a power source.

17. The system of claim 1 , wherein the extracorporeal cross-circulation circuit comprises a filter that permits return of blood cells directly to the host organism and perfusion of plasma through the extracorporeal organ.

18. A method of physiologic regulation of a extracorporeal organ, tissue or bioengineered graft via normothermic cross-circulation with a host organism, comprising
containing and supporting the extracorporeal organ, tissue or bioengineered graft in an extracorporeal organ chamber of the system of claim 1 , wherein the chamber comprises a time- and temperature-controlled humidifier and misting spray onto the organ, tissue or bioengineered graft and into the chamber to maintain a humid environment within the chamber; and
wherein the extracorporeal cross-circulation circuit of the system connects the extracorporeal organ, tissue or bioengineered graft with a host organism for cross-circulation of blood or plasma,

so as to thereby effect physiologic regulation of the extracorporeal organ, tissue or bioengineered graft via normothermic cross-circulation with a host organism.

19. The method of claim 18 , wherein the extracorporeal organ is a liver or lung.

Assignees

• Univ Columbia

Inventors

• Bacchetta Matthew
• Chicotka Scott
• Fung Kenmond
• Guenthart Brandon
• O'Neill John
• Vunjak-Novakovic Gordana

Classifications

• C12M41/16

  by recirculation of culture medium at controlled temperature · CPC title

• C12M29/14

  Pressurized fluid · CPC title

• C12M29/12

  Pulsatile flow · CPC title

• A01N1/16

  Physical preservation processes · CPC title

• A01N1/143 Primary

  for organ perfusion · CPC title