DE2531588C2 - Umbilical cord vessel transplants and their manufacture - Google Patents

Description

30th

The invention relates to the method for producing transplants as defined in the claims formed and hardened umbilical cord vessels of a mammal and the later it.! elderly transplants.

A major problem in vascular reconstructive surgery is the delivery of blood to organs and organs Tissues whose blood supply is either the result of congenital damage or acquired disorders gen is insufficient. z. B. through trauma. Atherosclerosis and the like. Originally, artery grafts were made Used by humans to ensure blood transport, but limited to Available quantity, the insufficient size * 5 outdoor areas. the development of aneurysms and atherosclerosis made the search for one more suitable replacement necessary.

Artificial grafts made of porous and pliable plastic have been made, but bring them that way this involves the following problems:

1. Infection in a foreign body graft is catastrophic, often causing bleeding. Sepsis and Death.

2. The inner surface can cause thrombosis and coagulation of the transplant as a consequence and can lead to an embolism of the clot.

3. The stiffness of the plastic layer can cause twisting and kinking, especially in the area «> of a joint.

4. Because of the risk of coagulation, artificial vessels with smaller diameters are often unusable.

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Other types of grafts that have tested with greater or lesser success are foreign grafts from cattle, according to Cutler. Bruce S., et al, The Modified Bovine Arterial Graft: A Clinical Study, Surgery 76,963 (1974) Cumulative Tolerance is not satisfactory In addition, it is expressly pointed out in this reference that So far, no vascular grafts have been performed with bovine arteries below the knee joint because the vessel kinks when the knee joint is bent

The following were also tested: collagen books that Both calf veins and self-graft were formed within the recipient patient where the This patient is the donor as well as a homograft where another person is the donor various substitutes also pose problems as they are difficult to obtain, small in size, of inconsistent size, time consuming to acquire, and problems with vascular valves, slight twisting, which can lead to occlusions, and tapers in the incorrect Direction. This last problem is particularly acute when calf veins are used as the veins Must be turned over when used for arteries so that the blood is in the opposite direction Direction flows

In view of the aforementioned difficulties, it is evident that there is an urgent need for one Vascular replacement is available in which these problems do not exist appear. In addition, it would be highly desirable to have such replacement parts stored and in A variety of different dimensions and shapes could be kept ready to use right out of the box to be. The invention solves this problem.

The mammalian umbilical cord contains structures that act as grafts in the vasculature or for others Lines can be used in the human body. The umbilical cord contains one vein and two Arteries surrounded by Wharton's jelly. Both the arteries and the vein are suitable for the Use in Surgery Compound grafts can come in various sizes and Molds are made.

The arteries and veins removed from the umbilical cords can be used fresh or after storage where they are either frozen or chemically preserved for storage. One treatment with antibiotics or other means of sterilization can be done. Although the formation of Antigens in these parts is low. treatment with enzymes can produce any antigenic substance be eliminated.

Generally, the cord is somewhat coiled and the arteries are twisted around the vein. Accordingly, mechanical or chemical treatment can be used to stretch the vein and the Arteries may be necessary.

When manufactured for use as veins and arteries, the Wharton's jelly can be either removed manually or by flushing with saline. A mandrel, which preferably is rejuvenated. can be inserted into the vein, after which the vein and arteries emerge easily from the Umbilical cord itself can be removed.

The advantages of the umbilical vessels, whether fresh or preserved, for processing into ducts or Reinforcement parts are as follows:

1. Easy availability.

2. high flexibility with no tendency to kink.

3. Distinctive strength, especially in ducts with a small diameter,

4. very soft, natural inner surface with a extremely low tendency to clot,

5. low tendency for infections,

6. low antigenicity

7. controllable diameter,

8. size choice for large and small vessels,

9. Sufficient length for virtually any use,

10. Adaptability to a wide variety of shapes including tapers and curves,

11. Compatibility with an external carrier in the form a mesh to reinforce larger vessels, soft under pulsating conditions be used,

12. Processability into upper layers to promote the Healing from surface trauma, such as wounds and Burns.

20th

Accordingly, the object of the invention is to provide an improved material for use as a vascular prosthesis, Reinforcement of organs, reinforcement of anastomas and acceleration of healing To provide surface trauma.

For a better understanding of the invention, reference is made to the drawings below further elaborated

F i g. 1 is a perspective view of an umbilical cord before treatment.

F i g. Figure 2 is a cross section through an umbilical cord on a cylindrical mandrel.

F i g. Figure 3 is a partial cross-section of a vessel made from an umbilical cord, hydraulically towards the inside pressed into a mold

Fig.4 is a cross section through a vessel from a Umbilical cord on a tapered thorn.

F i g. Figure 5 is a perspective view of a segment of an umbilical cord.

F i g. 6 is a side view of a vessel which is reinforced on one side by a segment in the form of a patch

Fig. Figure 7 is a cross-sectional view of an anastamosis reinforced by a segment in the form of a stripe.

F i g. 8 is a perspective view of an eyeball; where <ier area of transition into the retina in the Inside the eyeball is reinforced by a loop, this loop consisting of an umbilical cord-based vessel was formed.

If desired ODC ^r necessary, the vein or artery of the umbilical cord can be cut in the longitudinal direction and are assembled to form the composite parts of larger diameter. The umbilical cord vessel or part of it can be used after treatment to reinforce, support or seal a weakened area or damage to any part of the body, such as the heart, heart valves, bladder or to cover superficial wounds to promote healing.

Before removal from the umbilical cord, the blood vessels, particularly the vein, appear almost closed and quite small, as can be seen in Fig. 1, which shows an enlarged perspective view of part of an umbilical cord. The umbilical vein 11 and artery 12, as mentioned, are from FIG Surrounded by Wharton guests. Furthermore ', the arteries ⁴ sin 12 is rotated around the vein 11 and wound around and also contain the Hoboken-flaps. These are some factors that made the use of these vessels for grafts obscure. It has already been mentioned that the introduction of a dome into the vein 11 facilitates the removal of the remainder of the umbilical cord, but the arteries 12 can also be carefully cut out of the umbilical cord and pulled onto spikes. When this is done and they are sufficiently tanned, the Hoboken valves are removed. Vessels less than 1 mm in diameter can easily be made and permanently shaped using a suitable tanning solution. The umbilical vein is considerably larger than the arteries and can be stretched on a mandrel so that blood vessels with an internal diameter of even 1 cm can be created. Such vessels can of course be cut open and laid flat, in whatever condition they are suitable as patches for reinforcing organs, for completing anastomoses, and for covering superficial wounds.

After cutting out the appropriate vessel or of the vessels and the removal of residual blood they are for a few minutes, preferably 3 to For 10 minutes, sprayed with a hardener This step results in partial removal of the hobokf-i valves from the arteries. To the most suitable aldehydes include, for example, formaldehyde, glyoxal, dialdehyde starch and glutaraldehyde, being glutaraldehyde from the standpoint of preventing trace antigenicity and T.irombogenicity is most suitable and in second place is a solution of dialdehyde starch. The concentration of Glutaraldehyde solution is between 0.15 and 0.6%. The concentration of dialdehyde starch should be between 0.5 and 2.0 wt%. At lower concentrations, the glutaraldehyde solution will not make the material sufficiently non-antigenic, while at higher concentrations the reaction is too rapid runs and makes the walls of the vessel brittle

After treating a vessel with a hardening solution, the vessel is placed on a mandrel with a suitable Forni pulled. The blood vessel on the spine will then immersed in a vessel with hardening solution for 15 to 45 minutes, during which time the vessel adheres to the Adjusts the shape of the mandrel. A preferred solution for hardening is 0.5% glutaraldehyde solution, buffered with I% sodium bicarbonate so that the pH of the solution is between 7.5 and 8.5. The hardening agent causes that the blood vessel adapts to the shape of the dome, and also increases the strength of the vessel material. A vein 11 on a cylindrical mandrel 15 is shown in FIG.

Another means of forming a blood vessel w '* d η shown in Fig. 3, wherein a vein 11 in a tubular hollow form 18 is introduced, the end 19 of the vein 11 with the stopper 21 is locked. The other end 22 of the vein 11 becomes connected to TjHe 23 under moderate pressure for the introduction of hardening solution 16. The pressure of the Hardening solution 16 presses the vein 11 against the interior the shape 18 and adapts its shape. This procedure results in a blood vessel with a softer exterior.

The procedure of shrinking a vein or artery with a cylindrical mandrel 15 as in FIG F i g. 2 or a tapered mandrel 25 as in FIG. 4 has the advantage that any internal irregularities how the hoboken valves are eliminated, being

in Fig. 4 denotes a section of a vessel, which can be a vein or an artery, with 24. Small diameter arteries are especially valuable for replacing blood vessels in the body. the Umbilical cords from larger mammals contain larger vessels, making them larger and thicker-walled Vessels and pieces become available in this way. Smaller mammals make vessels with smaller ones Diameters available as required for special applications such as in fingers or toes are.

It should be noted that for the use of segments in pulsating blood vessels with internal Reinforcement with an artificial mesh is not necessary for diameters below about 2 mm. This follows not only from the fact that pipes with a smaller diameter can withstand greater pressures, but also from the fact that that when the vessels contract, the wall thickness c is reinforced. Soaking the vessels in alcohol prior to treatment in aldehyde will result in stiffer grafts.

After the vessel has hardened, it is pre-rinsed to remove most of the hardener. One A 10% solution of NaHCOi can be used for this purpose. The jar is then 30 to Treated 45 minutes with a reagent which reacts with remaining aldehyde. Suitable materials are amino acids, their alkali salts, hydroxylamine, peroxides, peracids and hypochlorites. the Amino acids as sodium salts and preferably L-sodium gluconate, L-sodium alanine. L-sodium phenylalanine and L-cysteine are particularly suitable for this purpose because they have an antithrombogenic effect, with am the glutamate works best. The mechanism is believed to be based on the condensation of the amino group the amino acid with the carbonyl group of the aldehyde is based. This leaves the carboxyl group des Free of condensate to give a negative charge to the surface of the vessel. Negatively charged Surfaces are known to be antithrombogenic.

It is stored in a solution of 40 to 50% aqueous alcohol containing about 1% Propylene oxide.

As is readily apparent, modifications of the procedure outlined above are possible: for example, after the vein has been flushed out of the umbilical cord, a spike, either tapered or straight, can be inserted into the vein, the cord frozen, the spike placed in a jig and all elements except the vein are ground away on a lathe. The outside of the vein can be ground down so that the wall thickness is tapered evenly or if desired. As expected, the vessel or vessel segment must be rendered sterile after such an operation. Common non-destructive techniques such as radiation. Antibiotics and elevated temperature can be used. An increase in the temperature up to 60 ^° C. during the tanning reaction also increases the speed of this reaction. The same technique can be used to remove any remaining traces of tanning agent.

Another modification is the vein slit open and lay flat. Using a flat dome makes it easier to create flat ones Segments. The vessel can then be cut into segments 20 of any desired size, as in FIG F i g. 5, such segments can be used as reinforcements or patches. One use one such segment is shown in Figure 6 where a vessel 26 which may be part of the intestines and sewn together to form a seam 27. This suture in the vessel 26 can be reinforced by a segment 29 is placed as a patch over the seam 27 and this is sewn to the vessel 26.

The function of such a patch is more than just reinforcement. As is well known. is it at

to sew together wall parts in body organs necessary not to pull the seams too tight and the Do not arrange the seams too tightly, otherwise the blood supply to the organ wall can be shut off which case a gangren can occur. As a result, using standard techniques, a The seam line in the wall leaks. It is for this reason that derivatives are used so often. A reinforcement of the seam, as in FIG. 6 shown largely reduces or completely avoids this risk.

Another possibility of using a segment is shown in Fig.7, which is an anastamosis in an intestine 31 shows. In accordance with standard surgical practice two ends 32 and 33 of the viscera 31 are turned inwards and the ends are then sutured with sutures 34 sewn together. A segment 36 is then placed around the junction between ends 32 and 33 sewn, whereby the risk of the intestinal contents seeping out into the abdomen is largely reduced or is turned off. Needless to say, there are two or more layers around the seam can be arranged, although F i g. 7 shows only a single layer from segment.

Segments can e.g. B. for lining the pericardium or another heart valve or for covering an artificial implant such as a pacemaker. Segments can also be in the plastic surgery can be used as an inert building material.

Although the tensile strength of a hardened vessel is only moderate. it has other properties that it is for make surgical use highly suitable. These are the non-antigenicity mentioned earlier and non-thrombogenicity as well as a characteristic flexibility, lubricity and complete compatibility with body organs and vessels.

There are a variety of surgical procedures in which the grafts are of great benefit

so can be used. It has already been mentioned that a segment is used to reinforce a seam and a Anastamosis can be used. It can also be used to reinforce a weak point or damage in an organ wall, such as B. the urinary bladder can be used. A segment can be shaped like this that it forms a beneficial connection between the bladder and the skin. A particularly important one Use as a rotinal loop around the eye. The need for such a noose occurs in the

ω surgical practice on when a detached retina should be restored. The manner in which an eye loop is used is in F i g. 8, where an eyeball 47 with a pupil 48 and the area 49 where a surgical procedure was made is shown. The area of intervention must be kept under pressure until the The retina has finally bound to the eyeball. For this purpose a loop 51 is made around the eyeball

twisted, so that the eyeball against the retina the inside of which is pressed. This generally requires that the internal pressure in the eyeball be reduced by about JO mm Hg is increased.

So far, retinal slings for the eye have been made from silicone plastic or fascia lata. That the first-mentioned material can. Erode the eyeball and cause an i.ifection. A certain fraction for this reason such interventions failed; as a result, blindness can occur. The usage of Fascia lata, on the other hand, requires an anterior one Operation to preserve the material. The replacement by one produced in the manner according to the invention Segment eliminates these difficulties. The material is fully compatible with the body and has no tendency to erode the eyeball.

Another important area of application for umbilical cord vessel grafts is in the Connection with Hauiirarispiaiiiaiiuiien. uuci one Burned or wounded skin, even if infected, can be a piece of this material be placed. In many cases, even a bandage is not necessary. The graft gets into the skin quickly integrated. The healing, including healing an underlying infection, takes place under the graft quickly instead of and without the need to change surgical dressings. When the cure is sufficiently advanced, the graft is rejected. It is of particular importance that this Temporary grafts can stay in place for a few months during the healing process.

The use of the transplants in humans or mammals thus brings numerous advantages, as can be seen from the above. The material is available in virtually unlimited quantities, and / μ its production required treatment is simple. Many modifications are also possible to suit specific requirements. As a result, sterile vessel segments can be manufactured in large quantities and at a low cost. They can be stored indefinitely and come in a variety of shapes and thicknesses to suit virtually any requirement. When stored in dilute glutaraldehyde solution, they only need to be rinsed in sterile water or saline or in dilute NaHCOi solution to be ready for use. If desired, they can also be rinsed in sodium L-glutamate to remove residual aldehyde.

When preparing for tanning and shaping, cleaning, rinsing or spraying liquids can be used passed through the veins and arteries of the umbilical cord. Solutions containing water, sterile saline, Ringer's lactate solution, hydrogen peroxide, sodium bicarbonate solution. Include alcohol and transplant perfusate solution. Antithrombogenic agents used for Treatment of the grafts that can be used include L-Sodium Glutamate, L-Alanine. L-phenylalanine. L-cysteine and L-lysine. These compounds are also used to treat vascular segments suitable for tanning to remove residues of the tanning agent.

Wharton's jelly can be wciucn mechanically or chemically using hyaluronidase to dissolve the riyiilutüi'iiüüi'c ii'i ucf Gäiici'ic cnifcmi. In addition, saline solution is effective for this purpose.

Mandrels for shaping the vessels can be made of glass, silicone plastic, stainless steel or another material inert to the vessels and the chemicals used in the process. The mandrel can be straight or curved, solid or hollow, cylindrical or tapered and smooth on its surface or be rough.

Especially when using larger vascular grafts with internal diameters greater than about 5 mm are to graze, it is desirable to reinforce these vessels by an outer covering of one Carrier net is attached. Both polyester and fluorocarbon plastics can be used the polyesters being preferred. Commercially available nets with large spaces (0.5 to 2.0 mm) can be wound around the vessels to give additional strength and support to the graft, with the mesh settling into the outer wall of the Graft embeds. A preferred form of such a mesh is a preformed tube.

Grafts reinforced by a mesh can be tested for their tightness and strength by they can be connected to a pulsation machine and solution with a pressure of 150 to 300 mm Hg is carried out.

For this purpose 2 sheets of drawings

Claims (5)

Patent claims: 1. Process for the production of grafts from shaped and hardened umbilical cord vessels of a mammal, characterized in that at least one of the main blood vessels an umbilical cord isolated, the blood vessel hardened with the help of an aldehyde and then with an amino acid, an alkali salt of an amino acid, a hydroxylamine, a peracid, a peroxide or treated with a hypochlorite to remove the residual aldehyde 2. The method according to claim 1, characterized in that that the blood vessel is hardened with a solution of glutaraldehyde in for 15 to 45 minutes a concentration of 0.15 to 0.6% by weight in Brings touch. 3. The method according to claim 1 or 2, characterized in that after curing a Prewash with water, saline or dilute sodium bicarbonate solution. 4. Transplants obtainable by the method of claims 1.2 or 3. 5. Transplants according to claim 4, characterized in that that they are reinforced on the outside by a flexible plastic net.