KR19990008070A - Apparatus and methods for sterilization, transplantation, culture, preservation, transport and testing of synthetic or natural vascular grafts - Google Patents

Abstract

An apparatus and method are described for sterilizing, endografting, culturing, storing, transporting and testing vascular endothelium. In particular, the present invention relates to apparatus and methods for transplanting and culturing human cells and vascular grafts. The device according to the invention comprises a fluid reservoir 10, a pump 12, an alternating pressure source 16 and at least one treatment chamber 14. By means of the alternating pressure exerted on the support structure 32 in the processing chamber 14 in which the vascular outgrowth skeleton 26 is placed, a variable radial stress acts on the skeleton 26. The stresses affect tissue-reinforced vascular epithelium with fibrous tissues and cells oriented to preserve natural blood vessels with normal physiological function and long-term dimensional stability.

Description

Apparatus and methods for sterilization, transplantation, culture, preservation, transport and testing of synthetic or natural vascular grafts

Vascular tissue grafts are used by vascular and chest tube surgeons to repair and replace arterial, venous blood vessels that are weakened or damaged due to diseases such as aneurysms, atherosclerosis, and diabetes. Historically, vascular tissue transplantation has been accomplished by implanting organs made of polyester (e.g., techron), expanded polytetrafluoroethylene (ePTFE) and other composite or biological tissue grafts, or allografts by patient's own saphenous grafts. This was done.

However, synthetic cuticles have inadequate conservation rates for many uses, while allografts are time consuming, expensive, and require major surgery that can shock the patient. Fixed breakfast transplants do not require transplantation by host cells, which is essential for tissue maintenance. As a result, fixed tissue transplants degrade over time and fail to function.

Because currently used synthetic and biological transplants are not suitable and allografts are limited in supply and expensive, tissue-enhanced transplants develop sterile, transplanted and cultured with cells. These tissue-enhanced grafts are superior to other tissue grafts used in prophylactic therapy because they remain stable for a long time and have a higher retention rate of natural blood vessels with normal physiological function.

Historically, transplantation and culture of blood and carp have been done in a static environment such as Petri Petri dishes. However, there are several drawbacks to transplanting and culturing tissue in this environment. For example, poor circulation of nutrients in static systems ineffectively slows transplantation and culture. In addition, cells transplanted and cultured in a dynamic environment maintain better physiological functions in the human body once transplanted. Thus, a dynamic environment is required to transplant and culture tissue-enhanced vascular grafts and other artificial organs.

The present invention relates to the sterilization, transplantation, culture, preservation, transport and testing of vascular grafts. In particular, the present invention relates to a device and a method in which the endothelium can survive with the cells by sterilizing the blood and endothelium after transplanting and culturing the endothelium and the endothelium.

1 shows a rapid apparatus of the present invention for extinction, endografting, culturing, storage transport and testing of an artificial organ;

2 shows a preferred alternating pressure source;

3 shows a device according to the invention for testing sterilization, transplantation, culture storage, transport of an artificial organ that can be processed simultaneously of multiple artificial organs;

4 shows another embodiment of an apparatus according to the invention for sterilizing, transplanting, culturing, storing and transporting an artificial organ;

* Code Description

10 ... fluid handling unit 12 ... pump

14 ... processing chamber 16 ... alternating pressure source

26 ... skeleton 28 ... inlet

30 ... outlet 32 ... tube

33 ... clip 36 ... valve

38 ... timer

It is an object of the present invention to provide a dynamic environment for transplanting, culturing and testing vasculature of various sizes and diameters.

It is another object of the present invention to provide an uncontaminated closed system for sterilizing, transplanting, culturing, preserving and transporting vascular endothelium.

In accordance with the present invention, an apparatus and method are provided for sterilizing, endografting, culturing, preserving, transporting and testing vasculature. The present invention relates to an apparatus and a method for transplanting and culturing blood and grafts so that cells and tissue-enhanced vascular grafts can survive.

The device according to the invention comprises a fluid reservoir, a pump, at least one carburizing chamber, a tube for holding carp in the processing chamber and an alternating pressure source for applying radial stress to the artificial organs in the processing chamber. Radial stress on the tube placed vascular endothelial skeleton in the treatment chamber during transplantation and incubation arranges the fibrous tissue and cells and vascular epithelium to maintain better physiological function in the human body. In this way, the present invention uses a mechanically simple device to create a dynamic environment for culturing tissue-enhanced vascular epithelium or other transplant organs.

The following examples according to the present invention describe devices and methods for sterilizing, endografting, culturing, storing, transporting and examining vascular endothelium, and those skilled in the art can readily apply the described methods and structures. It will be recognized. The same numbers are repeated in different figures, which represent the same parts in each figure.

1 shows a system for sterilizing, endografting, culturing, storing, transporting and testing vascular endothelium. According to a preferred embodiment of the invention, the system consists largely of a fluid reservoir 10, a pump 12, a treatment chamber 14 and an alternating pressure source 16.

Fluid reservoir 10 is used to store fluid in this system. Examples of suitable storage devices are sterilizable rigid receptors and Gibco-BRL 1 L incubators. The storage device 10 includes a filter to provide a gas source for the fluid in the system. Fluids that can be used in this system include sterile fluids, tanning fluids, fluids containing cells or fluids containing cultures. In a preferred embodiment, during the examination, transplantation, and incubation, the fluid advantageously consists of a fluid that remains the same as body temperature and has a viscosity that is about the same as the viscosity of the blood. An example of a fluid having a viscosity similar to blood viscosity is glycerol salts.

Fluid in fluid reservoir 10 is withdrawn via fluid line 18 by pump 12. Fluid line 18 and other fluid lines are in the form of medical tubes that are durable and suitable for transporting fluid when in use. The pump 12 is suitably a fluid pump capable of imparting a variable flow rate. Such pumps include the Masterflex L / S digital drive pumps manufactured by Cole-Palmer. Those skilled in the art can select a suitable pump from a variety of commonly used pumps. Pump 12 moves fluid through fluid line 20 from fluid reservoir 10 to process chamber 14.

The treatment chamber 14 is made of a biocompatible rigid material that can be sterilized, such as Teflon, polycarbonate, PVC and stainless steel. The treatment chamber 14 is composed of two parts, which are fixed by an adhesive or a male and female screw and are prevented from leaking. Observation is formed in the chamber to view the vascular epithelium in the treatment chamber 14, or the chamber is made of a transparent material such as polycarbonate or PVC. Inlet 28 and outlet 30 of process chamber 14 allow fluid to circulate through the chamber. Inlet 28 and outlet 30 allow fluid to circulate through the chamber. Inlet 28 and outlet 30 are used to secure process chamber 14 to fluid lines 20 and 22, respectively. Fluid line 22 connects fluid reservoir 10 and chamber 14 to create a closed system.

The treatment chamber 14 surrounds the inflatable tube 32 on which the vascular epidermal skeleton is placed. As will be described in detail below, the backbone 26 can be made from natural carp backbone materials as well as synthetic materials that do not cause rejection reactions. The tube 32 is made of a suitable elastomer, such as PET or a silicone balloon used for angioplasty, which is capable of expansion and contraction. The length and diameter of the treatment chamber 14 and the tube 32 can be varied to accommodate various lengths and diameters of the vasculature. This is useful when the system sterilizes, transplants, cultures, stores, transports and tests various types of vascular grafts, such as coronary, carotid, iliac and leg grafts. Porous clips or grommet 33 are disposed at both ends of the skeleton 26 in the tube 32 to keep the skeleton in place in the tube during processing. However, those skilled in the art will appreciate that various components other than clips or grommet may be used to hold the skeleton 26 in the tube 32. The grommet 33 is useful if the tube is made smaller than the diameter of the skin so that the fluid can circulate between the skin and the tube while preventing the carnival from slipping in the tube.

Tube 32 is expanded or contracted by an alternating pressure source 16, the signaled embodiment of which is shown in detail in FIG. In particular, FIG. 2 shows a pump 34 capable of providing positive and negative pressure (vacuum), such as a piston or diaphragm pump. The valve 36 receives positive and negative pressure through each line 40, 42 at the pump 34. In response to the signal generated by the timer 38, the valve 36 causes an alternating pressure to be applied from the line 24 to the tube 32. Valve 36 is to be applied. Valve 36 is in the form of an inline valve capable of regulating and controlling multiple pressure lines. Examples of such valves are MAC 45s, models 45A-AA1-DAAA-1BA.

By expanding and contracting the tube 32 with an alternating pressure source 16, the tube 32 exerts a variable radial stress on the vascular epithelium skeleton 26. This radial stress is advantageous because it is sensed by living cells attached to the skeleton, aligning the cells parallel to the stress axis and secreting extracellular matrix molecules arranged parallel to the stress axis. In this way, vascular endothelium is formed of fibrous tissues and cells that are made to have more resistant physiological physiology.

The system according to the invention comprises a plurality of chambers 14 for processing a plurality of vascular effusions. 3 shows a system according to the invention with two processing chambers 14. Although FIG. 3 shows only two processing chambers connected to the present system, those skilled in the art will clearly appreciate that several chambers can be connected to the present system in a similar manner. In particular, the line 20 can be divided to connect to each inlet 28, the line 24 can be divided to connect to each tube 32, and the line 22 to each chamber 14. It can be divided to be connected to the outlet 30 of the. In this way, many vascular grafts are transplanted, cultured or examined simultaneously.

Alternatively, each treatment chamber 14 may be connected to a separate fluid reservoir 10 and pump 12 so that it can be broadly divided into multiple treatment chambers and a single alternating pressure source 16 in the present system. It should be noted that in this system each treatment chamber 14 uses the same alternating pressure source and pump 12 but can be combined with other reservoirs 10 as pumps 12 with multiple pump lines can be used. .

7 shows another embodiment according to the present invention for sterilizing, endografting, culturing, storage transport and testing vascular grafts. According to this embodiment the system consists largely of a fluid reservoir 10, a bladder pump 50, a treatment chamber 46 and an alternating pressure source 54.

The fluid reservoir 10 and the fluid in the fluid reservoir are described in detail in FIG. 1. Fluid in the fluid reservoir 10 is withdrawn through the fluid line 60 by the bladder pump 50. Fluid line 60 and all other fluid lines of the present invention may be made from a medically durable tube suitable for receiving fluids when in use. Bladder pump 50 consists of hydraulic pump 51 and bladder 53, which is made of a suitable elastomeric material. A suitable bladder for example is a manual blood pump with a Cutter / Miles double valve. Bladder pump 50 is alternately compressed and inflated by alternating pressure source 54 with valve 52 and timer 55 through fluid line 58 from liquid reservoir to treatment chamber 46. Acts on the fluid. The alternating pressure source 54 is a device capable of imparting positive and negative pressure, such as a piston or a diaphragm pump. The valve 52 receives a positive (+) pressure and a negative (-) pressure at the pump 54 through lines 64 and 66. In response to the signal generated by the timer 55, the valve 52 may alternately apply positive and negative pressures from the line 62 to the bladder 53. The valve 52 is in the form of an inline valve capable of controlling multiple lines and determining the flow direction. These valves include the MAC 45S and Model 45A-AA1-DAAA-1BA.

When a negative pressure is applied to bladder 53, fluid is received from fluid reservoir 10 until bladder 53 is filled with fluid and fully inflated. While the bladder 53 is inflating, the check valve 72 will ensure that no force is applied to the fluid line 60. In this way, fluid circulating to the processing chamber 46 flows.

The treatment chamber 46 is made of a biologically suitable rigid material that can be sterilized, such as Teflon, polycarbonate, PVC and stainless steel. The processing chamber 46 is composed of two parts, which are fixed by adhesive or male and female threads and are leak-tight. Observation is formed in the chamber so that the vascular epithelium can be seen in the processing chamber 46, or the chamber is made of a transparent material such as polycarbonate or PVC. Inlet 68 and outlet 70 of processing chamber 46 allow fluid to circulate through the chamber. Inlet 68 and outlet 70 are used to secure process chamber 46 to fluid lines 58 and 56, respectively. Fluid line 56 connects fluid reservoir 10 and chamber 46 to form a closed system. Although only one processing chamber 46 is shown in FIG. 4, it should be appreciated that the fluid lines 56, 58, 60 may split to connect to one or more processing chambers in parallel with the system of the present invention.

The processing chamber 46 surrounds the porous tube 48 on which the vascular endothelial skeleton is placed. The skeleton 26 has been described in detail in FIG. 1. Porous tube 48 is made of a suitable rigid material, such as Teflon, PVC, polycarbonate, or stainless steel, through which fluid can pass. An example of a suitable porous tube is a porous plastic tube made by Porex Technologies. Porous tube 48 is made of a suitable elastomer, such as PET or a silicone balloon used in angioplasty, which allows fluid to pass through and expands and contracts. The length and diameter of the treatment chamber 46 and the tube 48 can be varied to accommodate various lengths and diameters of the vasculature. This is useful when the system sterilizes, transplants, cultures, stores, transports and tests various types of vascular endothelium. Porous clips or grommet 33 are disposed at both ends of the skeleton 26 in the tube 32 to keep the skeleton in place in the tube during processing.

If the tube 48 is made of a rigid porous material, the variable hydraulic pressure generated by the action of the bladder pump 50 will act on the fluid through the porous material. Hydraulic pressure through the porous material exerts a variable radial stress on the vascular endoskeletal. Or if the tube 48 is made of porous elastomeric material, the tube 48 expands and contracts the porous tube 48 with the bladder pump 50 imparted by the bladder pump 50, thereby reducing the tube 48. ) Applies a variable radial stress to the vascular epithelium skeleton 26. Again, like the rigid tube 48, the flow of fluid through the porous material of the elastomer will exert a variable radial stress on the framework 26. In this way, it exerts cyclic radial loads on the skeleton and cells, and vascular grafts are formed of fibrous tissue and cells made to have more resistant physiological functions in the human body.

Inlets and outlets of the processing chamber 14 (FIGS. 1, 3) and the processing chamber 46 (FIG. 4) may be sealed in a known manner (eg, luer lock or screw plugs) to prevent contamination of the sealed process chamber. You should know that you can. Sealing chambers can be used to sterilize, store and transport vascular epithelium and other organs. In particular, the vascular endothelial skeleton 26 fixed in the sealing chambers 14 and 46 before being placed into the system shown in FIGS. 1, 3 and 4 as a sealing chamber is characterized by chemical methods such as ethylene oxide or acetic acid peroxide, electron beam or gamma It will be sterilized by methods such as radiation or by steam sterilization. Sealed treatment chambers 14, 46 comprising sterile vascular endothelium skeletons are placed and opened in the systems shown in FIGS. 1, 3 and 4 for endograft and culture without contaminating the system of the present invention and vascular endothelium. do.

Implanting and culturing the vascular epithelium in the treatment chambers 14,46 can be performed in a known manner with another advantage due to the radial stress applied to the vascular epithelium during use. Examples of suitable transplants and cultures for three-dimensional cell culture growth are described in US Pat. 5,266,480, which is incorporated herein by reference. To establish a three-dimensional substrate, inject the substrate into the desired cells, and maintain culture. Patent NO. The techniques described in 5,266,480 are readily available to those of ordinary skill in the art.

Once the vascular epithelium reaches the desired cell density, it will be injected into the stock treatment chambers 14, 46. If the processing chamber is filled with a preservative, the inlet and outlet of the chamber are closed to form a closed chamber that can be used to store and transport cultured and preserved vascular endothelium. The preservative will be frozen in the chambers 14, 46 because the preservative is preferred for cryopreservation. In the manner described above, the sealing chambers 14 and 46 can be used to sterilize, incubate, store and transport vasculature or other organs.

Various embodiments of the invention have been described. The detailed description herein is merely exemplary and the present invention is not limited to the above examples. Therefore, it will be apparent to those skilled in the art that the present invention may be modified as described without departing from the scope of the following claims.

Claims (39)

A chamber having first and second portions through which fluid can flow; A support structure located within the chamber that is shaped and sized to support the tubular prosthesis; Device consisting of parts that impart radial stress to an artificial organ. The apparatus of claim 1 wherein the support structure is movable between a first position and a second position. The device of claim 2, wherein the radially stressing device comprises a component for moving the support structure between a first position and a second position. 4. The device of claim 3, wherein the support structure includes an expandable tubular member having an outer diameter that can vary with pressure in the tubular member, the tubular member adapted to receive a tubular artificial organ. 5. The device of claim 4, wherein the movable device includes an alternating pressure source connected to the tubular member for moving the support structure from the first position to the second position. The device of claim 1 wherein the support structure is made of a porous material. 7. The device of claim 6, wherein the stressing device is comprised of components that act to allow fluid to flow through the support structure. 8. The device of claim 7, wherein the fluid transfer device is comprised of a pump that applies alternating pressure. A chamber having a first portion and a second portion through which fluid can flow; A variable support structure located within the chamber that is shaped and sized to support the tubular artificial organ; The support structure can move between first and second positions, wherein the movement of the support structure can impart variable radial stress to the tubular artificial organ. 10. The device of claim 9, wherein the support structure comprises an inflatable member suitable for receiving a tubular artificial organ. The device of claim 10 wherein the inflatable member is comprised of an inflatable tubular member having an outer diameter that can vary with pressure in the tubular member. 12. The device of claim 11, wherein the inflatable member is made from an angioplasty balloon. 12. An apparatus according to claim 11, comprising an alternating pressure source connected with a tubular member for moving said support structure from a first position to a second position. 14. The pump of claim 13, further comprising: a pump to apply pressure at a first level and pressure at a second level; The alternating pressure source includes a valve connected between the support structure and the pump to alternately apply first and second levels of pressure to the support structure, the pressure of the first level affecting the first position and the second level of Pressure is applied to the second position. 15. The apparatus of claim 14, wherein the valve is connected to a timer for opening and closing the valve. 12. The device according to claim 11, wherein the inflatable tubular member is sized to separate the tubular member and the artificial organ at a first position to define a passage allowing fluid to circulate between the tubular member and the artificial organ. . 17. The device of claim 16, wherein the artificial organ is held in place on the support structure by a grommet. A housing defining a first and second portion through which fluid can flow and an endograft and culture chamber; A vascular endothelial support structure mounted within the chamber and adapted to support the vascular endothelial to allow fluid between the first and second portions to circulate around the endothelial surface; And An apparatus for transplanting and culturing vascular endothelium consisting of a pressure source for alternating expansion of the vascular endothelium support structure from a first position to a second position to exert variable radial stress on the endothelium. 19. The device of claim 18, wherein the vascular endothelial support structure is comprised of an elastic tube. 20. The pump of claim 19, further comprising: a pump for applying a first level of pressure and a second level of pressure; The pressure source includes a valve connected between the pump and the support structure to alternately apply pressure of the first and second levels to the support structure, the pressure of the first level pushing the support structure to the first position and the second The pressure at the level pushes the support structure to the second position. 19. The apparatus of claim 18, comprising a plurality of housings. 19. The device of claim 18, wherein the first and second portions of the housing can be sealed to receive, sterilize, store and transport vascular endothelium. A housing defining a first and second portion through which fluid can flow and an endograft and culture chamber; And A porous vascular epithelial support structure mounted to the chamber and connected to the first position such that fluid flows out of the second position through the porous support structure at the first position; Wherein the flow of fluid through the support structure exerts radial stress on the carcass mounted on the support structure. 24. The device of claim 23, comprising a pump for applying a variable pressure to the fluid flowing into the housing. The apparatus of claim 24 wherein said pump is a bladder pump. 23. The apparatus of claim 22, wherein the support structure is a rigid porous tube. 23. The apparatus of claim 22, wherein the support structure consists of an elastic porous tube. Exposing the artificial organ to a fluid for internal transplantation and culture; Applying radial stress to the tubular organs during endografting and culturing to arrange the cells in the desired form in the artificial organs. 29. The method of claim 28, further comprising: in the step of applying radial stress, placing the artificial organ in a support structure; Moving the support structure between the first and second positions to impart radial stress to the artificial organ. 졔 29. The method of claim 29, wherein the support structure is made of an elastic tube. 31. The method of claim 30, wherein in the step of inflating the support structure the tube is moved from the first position to the second position by means of a pump which in turn exerts a first level pressure and a second level pressure. Way. 29. The method of claim 28, wherein in the step of applying radial stress, the artificial organ is disposed in the porous support structure; Acting on the fluid to pass through the porous support structure such that radial stress is imparted from the fluid to the artificial organ. 33. The method of claim 32, wherein the porous support structure is made of a rigid tubular member. Having a fluid source; Pumping fluid from the fluid source to move the fluid; Supporting the artificial organ in a chamber that is connected rather than fluid flow; A method of processing a tubular artificial organ, comprising moving the artificial organ from a first contracted position to a second expanded position when fluid flows. 35. The method of claim 34, wherein the diameter of the artificial organ can be changed by moving the artificial organ. 36. The method of claim 35, wherein the supporting step comprises positioning an artificial organ relative to the elastic tube in the chamber and the variable actuation step comprises moving the tube from the first inflated position to the second retracted position. Way. 37. The method of claim 36, wherein a pump is used to move the tube from the first expanded position to the second retracted position, wherein the pump alternately applies first and second levels of pressure to the tube. 36. The method of claim 35, wherein in the supporting step, an artificial organ is placed relative to the porous tube structure in the chamber and a variable pressure is applied to the fluid through the tube structure during the variable movement phase of the artificial organ. 39. The method of claim 38, wherein a pressure is applied to the fluid through the tube structure using a pump, the pump applying pressure to the tube structure at first and second levels.