PRESSURIZED SYSTEM FOR TISSUE TRANSPORT AND PRESERVATION

Abstract

Systems and methods of the invention generally relate to prolonging viability of bodily tissue, through the use of pressurizer element operable in a sealed organ transport system purged of air and filled with preservation fluid. The pressurizer element is operable to capture and maintain pressure from a fluid-fill line during set-up of the container. Increased pressure within the container reduces edema in the organ during storage and transport by providing a compressive force on the organ.

Claims

1. A system for storage of an organ, the system comprising: a sealable organ container comprising a vent port, and internal volume, and a fill port; a pressurizer in fluid communication with the sealable organ container operable to provide an increased internal volume for the sealable organ container in response to increased fluid pressure within the sealable organ container; and a fluid source in fluid communication with the fill port through a fill valve.

2. The system of claim 1, wherein the organ is a heart.

3. The system of claim 1, wherein the pressurizer comprises a bellows.

4. The system of claim 3, wherein the pressurizer provides an increased internal volume for the sealable organ container by expanding in response to increased fluid pressure within the sealable organ container.

5. The system of claim 3, wherein the pressurizer provides an increased internal volume for the sealable organ container by compressing in response to increased fluid pressure within the sealable organ container.

6. The system of claim 3, wherein the bellows is spring-energized.

7. The system of claim 1, wherein the pressurizer is disposed between the fill valve and the fill port.

8. The system of claim 1, wherein the pressurizer is disposed on an external wall of the sealable organ container.

9. The system of claim 5, wherein the pressurizer is disposed entirely within the sealable organ container.

10. The system of claim 1, wherein the pressurizer comprises an elastomeric material resistant to expansion and disposed in a fill line between the fill valve and the fill port.

11. The system of claim 1, wherein the sealable organ container is rigid.

12. The system of claim 1, wherein the organ container is plastic and becomes rigid upon being filled with fluid.

13. A method for storage of an organ, the method comprising: providing an organ storage system comprising: a sealable organ container comprising a vent port, and internal volume, and a fill port; a pressurizer in fluid communication with the sealable organ container operable to provide an increased internal volume for the sealable organ container in response to increased fluid pressure within the sealable organ container; and a fluid source in fluid communication with the fill port through a fill valve; sealing an organ within the sealable organ container; opening the vent port; elevating the fluid source above the sealable organ container; opening the fill valve to allow fluid from the fluid source to flow into the sealable organ container; closing the vent port upon fluid escaping therefrom; energizing the pressurizer with fluid pressure from the elevated fluid source; closing the fill valve; and disconnecting the fluid source from the fill valve.

14. The method of claim 13, further comprising elevating the fluid source at least 50 cm above the sealable organ container.

15. The method of claim 13, wherein the pressurizer comprises a bellows.

16. The method of claim 15, wherein the bellows is spring-energized.

17. The method of claim 13, wherein the pressurizer is disposed between the fill valve and the fill port.

18. The method of claim 13, wherein the pressurizer is disposed on an external wall of the sealable organ container.

19. The method of claim 13, wherein the pressurizer is disposed entirely within the sealable organ container.

20. The method of claim 13, wherein the pressurizer comprises an elastomeric material resistant to expansion and disposed in a fill line between the fill valve and the fill port.

21. The method of claim 13, wherein the sealable organ container is rigid.

22. The method of claim 13, wherein the sealable organ container is plastic and becomes rigid upon being filled with fluid.

23. The method of claim 13, wherein the organ container comprises an elastomeric material resistant to expansion and acts as a pressurizer upon being filled with fluid.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] FIG. 1 shows a prior art organ transport arrangement.

[0015] FIG. 2 shows a prior art organ transport canister.

[0016] FIG. 3A shows an organ transport system with an unengaged bellows-type pressurizer in the fill neck.

[0017] FIG. 3B shows an organ transport system with an engaged bellows-type pressurizer in the fill neck.

[0018] FIG. 4 shows an exemplary method of filling and pressurizing an organ transport canister.

[0019] FIG. 5A shows an organ transport system with an un-engaged bellows-type pressurizer in the canister.

[0020] FIG. 5B shows an organ transport system with an engaged bellows-type pressurizer in the canister.

[0021] FIG. 6A shows an organ transport system with an un-engaged balloon-type pressurizer in the fill neck.

[0022] FIG. 6B shows an organ transport system with an engaged balloon-type pressurizer in the fill neck.

[0023] FIG. 7 shows a free-floating bellows-type pressurizer.

[0024] FIG. 8A shows an organ transport system with an un-engaged free-floating bellows-type pressurizer in the canister.

[0025] FIG. 8B shows an organ transport system with an engaged free-floating bellows-type pressurizer in the canister

DETAILED DESCRIPTION

[0026] Devices, systems and methods are described herein that are configured for extracorporeal preservation and transportation of bodily tissue. Specifically, devices and methods for creating and maintaining pressure within organ storage and transport containers are described. Systems and methods can be used to reduce edema in transported organs by maintaining an increased pressure in the surrounding fluid to prevent swelling by applying a compressive force to the organ. It is thought that the increased pressure further approximates the internal conditions of the human body to which the organ is usually subjected, thereby prolonging organ viability during storage and transport.

[0027] A controlled thermal environment can be maintained for the organ through the use of a rigid container completely filled with preservation fluid and purged of air. Systems can be filled with fluid at an increased pressure derived from mechanical pumping or through elevation of the fluid source. In order to adjust and maintain a desired pressure in the range of about 25 to about 50 cm H.sub.2O given a rigid container and a relatively incompressible fluid within the container, systems and methods of the invention use a pressurizer to introduce a desired level of volumetric compliance. The resistance to compression in bellows-type pressurizers or to expansion in balloon-type pressurizers can be selected to achieve and maintain the desired pressure within the system. The resistance can manipulated as a function of material choice, spring-rate, gas volume (e.g., in gas-energized bellows) to achieve the desired pressure within the system.

[0028] The system may use any of a number of cooling media to maintain the temperature inside an insulated transport container during transport. Cooling media may comprise eutectic cooling blocks, which have been engineered to have a stable temperature between 2-10° C., for example. The cooling media can be arranged in recesses in the interior of the insulated vessel. The recesses may be a slot or the recess may be a press-fit, or the cooling media may be coupled to the walls of the insulated vessel using a snap, screw, hook and loop, or another suitable connecter. Eutectic cooling media suitable for use with the invention is available from TCP Reliable Inc. Edison, N.J. 08837, as well as other suppliers. Other media, such as containerized water, containerized water-alcohol mixtures, or containerized water-glycol mixtures may also be used. The container need not be rigid, for example the cooling media may be contained in a bag which is placed in the recess. Using the cooling media, e.g. eutectic cooling blocks, the invention is capable of maintaining the temperature of the sample in the range of 2-10° C. for at least 60 minutes, e.g., for greater than 4 hours, for greater than 8 hours, for greater than 12 hours, or for greater than 16 hours.

[0029] In various embodiments, cooling blocks may include eutectic cooling media or other phase change material (PCM) such as savENRG packs with PCM-HS01P material commercially available from RGEES, LLC or Akuratemp, LLC (Arden, N.C.). Exemplary PCM specifications including a freezing temperature of 0° C.+/−0.5° C., a melting temperature of 1° C.+/−0.75° C., latent heat of 310 J/g+/−10 J/g, and density of 0.95 gram/ml+/−0.05 gram/ml. Pouch dimensions may vary depending on application specifics such as tissue to be transported and the internal dimensions of the transport container and external dimensions of the tissue storage device, chamber, or canister. PCM may be included in pouches approximately 10 inches by 6 inches having approximately 230 g of PCM therein. Pouches may be approximately 8.5 mm thick and weigh about 235 g to 247 g. In some embodiments, pouches may be approximately 6.25 inches by 7.75 inches with a thickness of less than about 8.5 mm and a weight of between about 193 g and about 201 g. Other exemplary dimensions may include about 6.25 inches by about 10 inches. Pouches may be stacked or layered, for example in groups of 3 or 4 to increase the total thickness and amount of PCM. In certain embodiments, PCM containing pouches may be joined side to side to form a band of coupled PCM pouches. Such a band may be readily manipulated to wrap around the circumference of a cylindrical storage container and may have dimensions of about 6 inches by about 26 inches consisting of approximately 8 individual pouches joined together in the band. Pouches may be formed of a film for containing the PCM having a desirable moisture vapor transmission rate to avoid PCM mass loss over time. Suitable films include X2030 EVOH and nylon pouch film available from Protect-all (Darien, Wis.) and pluss plain laminate 162μ OP nylon multilayer film 350 mm available from Shrinath Rotopack Pvt. Ltd. (India).

[0030] As shown in FIGS. 1 and 2 and noted above, rigid containers, purged of air (FIG. 2), provide benefits over typical bags (FIG. 1). Specifically, the container shown in FIG. 2 and similar containers detailed in U.S. Pat. No. 9,426,979 provide significant advantages in temperature control for the enclosed environment and also provide a deeper fluid well resulting in greater bulk pressure of the fluid on the organ in the canister embodiments in FIG. 2. Observations using canisters similar to that shown in FIG. 2 indicate that factors other than temperature control are contributing to better-than-expected organ condition following transport. Upon examination, it is believed that the greater fluid pressure in the canister reduces organ edema and contributing to the positive results.

[0031] In order to generate and maintain greater pressure (above the 8-20 cm H.sub.2O observed in rigid canisters such as shown in FIG. 2), systems and methods of the invention use a variety of pressurizers, examples of which are shown in FIGS. 3 and 5-8.

[0032] Two components can be added to a purging canister transport system such as shown in FIG. 2 to achieve the desired pressures. First, a compliant, compressible pressurizer element, wetted on one side (internally or externally) and energized by elastic deformation (of metal, elastomer, or gas). Second, a fill valve can be added at a fill port or along fill line in order to close off and capture the in-line pressure of a fluid during filling. Any valve can be used including manually controlled ball, butterfly, choke, diaphragm, gate, globe, knife, needle, pinch, piston, or plug valve. In certain embodiments a simple rolling clamp such as used on intra-venous tubing may be used on the fill line. In some embodiments, a leak-proof quick-disconnect coupling may alternatively be used for the fill valve. In some embodiments an automatic one-way check valve may be used to allow fluid to flow in until the pressure is equalized across the system and flow stops. In such embodiments, the purge valve must be closed once the system has filled with fluid and all air has been purged from the canister to prevent further outflow of fluid and allow pressure to build in the container.

[0033] An exemplary pressurizer element is shown in FIG. 7 comprising a bellows configured to compress in response to external pressure. The pressurizer element resists compression and, through that resistance, maintains a pressure in the surrounding fluid by reducing the volume that the fluid would otherwise fill. The resistance of the pressurizer may be provided through the use of an elastomeric material such as a medical-grade rubber or may be imparted by a spring contained within the pressurizer element as shown in FIG. 7. In some embodiments the pressurizer may be filled with a compressible gas and the resistance of that gas to compression can impart the resistance to volumetric expansion of the container and the resulting increased fluid pressure therein. The resistance and range of travel should be selected to correspond to the desired range of pressures desired in the container during transport such that the pressurizer is responsive to the in-line filling pressure but does not fully compress or expand upon exposure to the pressure ranges discussed herein.

[0034] The bellows may rely on inherent shape memory in the material of the bellows itself to provide resistance to expansion or compression or may use, for example, springs opposing the expansion or compression of the bellows via compression or tension. Any known spring type may be used including coiled materials or elastic bands to provide expansion resistance. The expansion- or compression-resisting force may be a single rate or may be progressive or adjustable. In various embodiments, a constant force spring can be used to maintain system pressure. Constant force springs are springs for which the force they exert over their range of motion is relatively constant. Constant force springs may be constructed from rolled ribbons of, for example, spring steel.

[0035] In certain embodiments, the pressurizer can, instead of passively maintaining pressure, be used to actively create pressure by, for example, manually compressing a bellows-type pressurizer, filling the container with fluid, sealing the container, and manually releasing the compressed pressurizer. The pressurizer can thereby create additional pressure above the in-line pressure of the fill fluid.

[0036] FIG. 3 shows an in-Line pressurizer 103 using a spring-energized bellows in unengaged (FIG. 3A) and engaged or energized (FIG. 3B) configurations. The bellows are externally wetted meaning that external fluid pressure compresses the bellows. In FIG. 3A the fill valve 105 is opened, allowing fluid to fill the container 101 until all air is purged from the system through a one-way purge port in the container lid. In FIG. 3B, the purge port has closed and the container 101 is filled with fluid. The pressurizer 103 has compressed in response to the in-line pressure from the fluid. The fill valve 105 has been closed, thereby trapping the fill pressure within the container 101. That pressure is maintained by the expanding force of the pressurizer 103. The in-line pressure of the fluid can be imparted through elevation of the fluid source above the container 101 or through mechanical pumping or other pressurizing means.

[0037] An exemplary filling procedure according the certain methods is illustrated in FIG. 4. An elevated fluid source (in the illustrated case, a bag of preservation solution) is used to create in-line fluid pressure. The fluid source can be elevated at least 50 cm above the container. The final distance can be selected based on the final transportation pressure desired in the container. The pressurizer, as shown in FIG. 4, is an internally-wetted spring-energized bellows. As opposed to the externally-wetted bellows shown in FIG. 3, the internally wetted bellows is compressed by the energizing spring and expands in response to fluid pressure on the inside of the bellows. The spring resists the expansion and maintains the pressure in the system once the fill valve is closed.

[0038] During set-up in FIG. 4, the elevated fluid source is connected, via the in-line fill valve, to the container system with the organ therein, the lid sealed, the vent port open, and the pressurizer empty. The fill valve is opened to allow fluid to enter the system. As fluid fills the system, trapped air escapes through the open vent port (or purge port or valve) in the container lid. When all the air has been purged, fluid will escape through the vent port. In response to observing fluid escaping through the vent port, a user can close the vent port. Alternatively, an automatic vent port can be used for example comprising a material that, when wetted, expands to close the port.

[0039] Once the vent port is closed, pressure will be allowed to build within the system to equal the in-line pressure caused by the elevated fluid source. The pressurizer will thereby be energized, expanding (or compressing in other embodiments) in response to the force of the fluid pressure within the system. Once the pressurizer is energized, the fill valve can be closed, thereby sealing the system and maintaining a pressure within the container equal to the in-line pressure from the elevated fluid source through the spring-energized resistance of the pressurizer. A pressure gauge can be positioned along the system (e.g., on the canister, on the fill line, or in the pressurizer to allow for monitoring and management of the internal pressure in the canister during set up and transport. In certain embodiments, the pressurizer may be variably compliant (e.g., have an externally adjustable spring rate) to allow pressure to be changed within the system after the container is filled and sealed.

[0040] After the fill valve is closed, the fill line to the fluid source can be disconnected and the container is ready for transport.

[0041] FIGS. 5A and 5B show an in-lid pressurizer using an externally-wetted, spring-energized bellows affixed to the lid and extending into the organ compartment. Externally-wetted pressurized bellows are inherently stable and are resistant to buckling. In FIG. 5A the fill valve is open and the pressurizer has not been energized. FIG. 5B shows an energized pressurizer in response to the in-line pressure from the fill line where the fill valve has been closed to trap in the fluid pressure.

[0042] FIGS. 6A and 6 B show an in-line pressurizer using an elastomeric balloon which inflates during the filling process and is energized by stretching of the in-line material (e.g., the balloon). The material's inherent resistance to expansion or stretching provides the resistance to mechanically maintain the pressure in the system once the fill valve is closed as in FIG. 6B. FIG. 6A shows an un-expanded pressurizer and open fill valve during the filling process. In certain embodiments, the container itself may comprise an elastomeric balloon in which the tissue or organ is disposed before filling with preservation fluid. The walls of the container can therefore act as a pressurizer capturing the fluid pressure during filling through expansion against an elastic resistance.

[0043] FIGS. 8A and 8B show a floating pressurizer using either a spring-energized or gas-energized bellows. The pressurizer may be designed such that it sinks when compressed giving a clear visual indication that the system is properly pressurized. In order to accomplish that, the density of the pressurizer when compressed should be greater than the density of the pressurized solution. The floating pressurizer can be tethered to the surface of the container to prevent contact with the organ and potential damage thereto during transport.

[0044] Materials for valves and pressurizers, wherever surfaces may contact the preservation fluid or the organ to be transported, should be selected based on biocompatibility and inertness with respect to the preservation fluid. Considerations such as sterility and ability to be sterilized are also used in material selection.

INCORPORATION BY REFERENCE

[0045] References and citations to other documents, such as patents, patent applications, patent publications, journals, books, papers, web contents, have been made throughout this disclosure. All such documents are hereby incorporated herein by reference in their entirety for all purposes.

EQUIVALENTS

[0046] Various modifications of the invention and many further embodiments thereof, in addition to those shown and described herein, will become apparent to those skilled in the art from the full contents of this document, including references to the scientific and patent literature cited herein. The subject matter herein contains important information, exemplification and guidance that can be adapted to the practice of this invention in its various embodiments and equivalents thereof