DE2350050C2 - Moldings made of plastic that are compatible or harmless for biological tissue and cell tissue cultures - Google Patents

Description

The invention relates to a compatible or harmless for biological tissue and cell tissue cultures Molded body made of plastic.

The ever increasing use of plastics for instruments or devices that come into contact with biological substances has led to considerable difficulties, as most plastics are toxic to biological tissue or cell tissue. The toxicity is due to the fact that the plastic itself is toxic or that it contains, for example, toxic plasticizers, catalysts or initiators. If the toxic plastics are brought in compact with biological systems, this is it Plastic is responsible for the growth of the cells that come into contact with the plastic inhibited or prevented the reactions from being rejected or rejected or that allergic reactions or the growth of tumors.

One field in which this problem is particularly very serious is the culture or breeding of Cell tissues.

In the past, glass containers were used in this field, whereas nowadays there is a tendency to As in the field of bacteriology, plastic containers or gels are closed use.

Cell tissue cultures are very sensitive to toxic substances present in the container walls. It Considerable efforts have already been made to improve the "compatibility" of plastic containers to improve biological tissue. Most used in conjunction with tissue culture techniques Containers are transparent so that it is possible to see the result of tissue culture or tissue cultivation ascertain. It is therefore essential that any improvements in the compatibility of the Plastic container with the tissue culture does not affect the necessary degree of transparency.

ίο An essential area of use of Plastics is the medical or surgical field, in particular with regard to the insertion of Plastic implants in the body. Plastic implants usually get rid of that quickly Body repelled or refused, whereby they are also responsible for local inflammation and irritation are, whereby the healing process is impaired and the treatment result is worsened.

In order to solve the problem in the tissue culture field, it is necessary become. Use containers or objects made of glass or a specially treated plastic, z. B. Containers or objects made of polystyrene that have an outer layer made of a transparent material have, which is not toxic to biological tissues. This last-mentioned alternative the price of the container or object is increased considerably so that the use of such Article narrow limits are set.

jo implants are usually made of metal. the Experience shows that certain metals, such as

■ Tantalum, are compatible with biological tissues. The manufacturing price of such an implant is very high high, which is disadvantageous from an economic point of view. The thermal conductivity of the metal continues to lead to physical discomfort, for example if the patient is undergoing shortwave treatment.

It is also from William Goldie "Metallic Coating of Plastics" (1968), especially pages 39 bis 49, an electroless catalytic plastic plating known, by sensitizing for example with Sn (II) salts in a first stage, activation, for example, with a Pd salt in a second stage and finally applying the final metal layer in a third stage.

From this known three-stage process, however, there is no indication of tissue compatibility derive the finally obtained plastic molding.

The invention is based on the object of a per se for biological tissue and cell tissue cultures intolerable or harmful plastic tissue-compatible to rwache with partial application of the Process steps of the known metallization process.

According to the invention, this object is achieved in that at least the ones in contact with the tissue The upcoming molded body surface is provided with a noble metal coating, which by sensitizing the

ho plastic and subsequent treatment with a LiHung of the corresponding noble metal salt applied is.

In order to obtain a plastic molded body with a tissue-compatible surface, according to FIG

The invention taught that known metallization processes to be completed prior to the third treatment stage essential for this process, essentially according to the method known per se

upstream sensitization and activation stages. According to the invention it was recognized that these two Steps are sufficient to make a tissue-incompatible plastic tissue-compatible.

According to a preferred embodiment, the plastic or the surface of the plastic body is provided with a precious metal label, which after sensitization of the plastic is applied with a tin salt or tin (II) oxide. After another The invention is embodied in the plastic or the surface of the plastic body with a noble metal coating provided by treatment with a solution of a salt based on gold, rhodium, Platinum or palladium is applied.

The plastic molding expediently consists of a transparent plastic, in particular made of polystyrene, polyacrylonitrile or mixed polymers.

In order to find out the "compatibility" of various coatings with biological tissues, different containers tested. Five different cell chains were used in these experiments, namely the normal cell chain FBL (L) produced by the human embryo lung, which is commercially available Fiber incendiary line WI-38 and three tumor cell lines, namely one from a lung tumor CA (L) fast growing cell line derived from, one osteogenic sarcoma cell line OS-138 and one Cell line derived from MG-105 malignant glioma. The culture medium used was "Eagles Medium" with 10% calf serum.

Three different types of plastic Petri dishes were used, namely dishes P treated according to the invention and metallized with platinum, a commercially available dish without a metal coating, but with a different! Transparent coating F was provided and an untreated sample dish K. The dishes with a different type of transparent coating F were representative of the dishes which were previously regarded as the most suitable dishes in the available area.

The tests were carried out taking into account three different properties, namely:

1. Adhesion effect (= A.E.). The test was carried out by placing 1000 cells per plate in a culture bez. Nutrient medium were introduced, wöbe; the

in growth of the cells was one, two or four calendar days. At the end of the growing season the cell tissue culture medium was aspirated and the cells on the bottom of the plate with Methanol fixed and using standard techniques

π colored. The test result was determined by

the number of adherent cells was counted.

2. Propagation Effect (C.E.). In this test, 1000 cells were introduced into each plate and. after 10 days was the number of cell colonies

counted in that contained more than 25 cells. Coherent cell colonies that contained a large number of cells (e.g. 200-300) were counted as one colony because it can be assumed that such a colony would begin

2-, borrowed several cells and therefore contained

did not in itself constitute a criterion for improved growth.

3. Speed of growth. 20,000 cells were grown on plates, which on the one hand according to the

were trained in invention and on the other hand by

were of the type with a different type of transparent coating. The cells were from the Plates removed after 1, 2, 5, 6, 7, 8, 10, 13 and 17 days and placed in a so-called cell scope

j-, counted.

The cling effect for cell strings WI-38, FBL (L), MG-105, OS-138 and CA (L) is in Table 1 shown.

Table 1

"Anhaft-EfTekt" of the cell chain WI-38, FBL (L), MG-105, OS-138 and CA (L).

Petri dish

Calendar day after the WI-38 Wind up

FBL (L)

MG-105

OS-138

CA (L)

170 229 140 231 227 400 408 111 32 320 834 620 0 35 480 182 223 197 201 182 279 401 504 307 497 2731 1632 2428 1427 2692 209 164 307 199 265 321 392 608 307 454 1039 1724 1432 2031 2323

As can be seen from the table, the initial sticking effect is essentially the same for the three types of Petri dishes used, although the persistence of the sticking effect is lower in the case of the types of Petri dishes than in the case of dishes P which are metallized with platinum according to the invention are, or as with the shells F with a different type of transparent coating. The trays P according to the invention apparently have a slightly better adhesive effect after four days than the trays F with a different type of transparent coating. although in this respect it must be assumed overall that the bowls P according to the invention and the bowls F with a different type of transparent coating have essentially the same adhesive effect.

Multiplication Effeki

The proliferation effect of the cell chains is shown in Table 2.

Table 2

Multiplication effect of the cell chains WI-38, FBL (L) ₁ MG-105, OS-138 and CA (L).

Petri W! 08 FBL (L) MG-105 OS-I33 CA (L) peel K 8th 0 0 4th 7th P. 59 35 64 28 44 F. 42 36 49 11th 18th

As can be seen from the table, the platinum coating has a considerably increased multiplication effect.

The difference in the propagation effect between the dishes F with a different type of transparent coating and the dishes P metallized according to the invention with platinum is less pronounced, although the growth capacity of most cell chains appears to be greater in the case of plastic metallized with platinum than in dishes with a different type of transparent coating, whereby however, there is an exception to the chain FBL (L).

Growth rate

With the respective cell chains, a comparison was made between platinum-plated plates and the like Plates with a different type of transparent coating carried out and it was found that the Growth rate and the final saturation index for the three tumor cell lines and the normal cell chains in the same order of magnitude for both the platinum-plated shells and the bowls with a different type of transparent coating <! lay. It cannot be determined that there is a final saturation index. It however, it can be determined that the cell chains have the same growth opportunity in platinum metallized Trays and trays with a different type of transparent coating, while the untreated ones Shells inhibit or prevent growth.

The tests show that a plastic metallized with platinum, taking into account the sticking effect provides an improvement in terms of the "compatibility" of the material with biological tissues. One with Platinum metallized plastic considerably improves the ability of cells to grow, known as Multiplication effect. In most of the culture or breeding experiments, the growth rate was of the cell chains on plastic dishes metallized with platinum as well as on the commercially available ones available bowls with a different type of transparent coating the same.

The dishes according to the invention used in the experiments consisted of polystyrene which had been treated with a platinum salt. Containers made of other plastics such as polymethacrylate and polyethylene, which in themselves inhibit or prevent cell growth, were tested in other series of tests. It was found that these containers, after being coated with platinum, had properties comparable to those of the dishes used in the above-mentioned experiments and manufactured according to the invention. Tests have been carried out in a similar manner with dishes which have been metallized with other metals such as gold, palladium and rhodium, with likewise good results.
A method by which Petri dishes of the type discussed above and exposed to the tests can be produced is now described with reference to the following example.

example

Treatment of plastic trays with platinum salt

Several plastic dishes made of polystyrene with a diameter of 5 cm were treated with 0.5 ml of a solution for ^{30 seconds at a temperature of 20 ° C.}

Treated that by dissolving 100 mg of tin-II fluoride in a mixture of 200 ml of methanol and 5 ml of acetone. After this treatment

step the dishes were washed with 1 ml of ethanol.

Then 0.5 ml of an ethanol solution containing 2% water and 0.1 mg platinum chloride were added.

The solution was then allowed to act on the plate at about 30 ° C. for one minute before the dish emptied and air dried.

After the dishes had been coated with metal in the manner described, they were sterilized ^{in sealed packs by gamma radiation, for example radiation of 60 Co.}

Claims (5)

Patent claims: 1. Shaped bodies that are compatible or harmless for biological tissue and cell tissue cultures made of plastic, characterized in that at least those in contact with the fabric The upcoming molded body surface is provided with a noble metal coating, which by sensitizing the Plastic and subsequent treatment with a solution of the corresponding precious metal salt is applied. 2. For biological tissue and cell tissue cultures compatible or harmless shaped body according to claim I _1, characterized in that it is provided with a noble metal coating, which is applied after sensitizing the plastic with a tin salt or tin (II) oxide 3. Shaped bodies that are compatible or harmless for biological tissue and cell tissue cultures according to claim 1 or 2, characterized in that it is provided with a noble metal coating, the by treatment with a solution of a salt based on gold, rhodium, platinum or palladium is applied 4. Shaped bodies that are compatible or harmless for biological tissue and cell tissue cultures according to one of claims 1 to 3, characterized in that it is made of transparent plastic consists 5. Shaped bodies that are compatible or harmless for biological tissue and cell tissue cultures according to one of claims 1 to 4, characterized in that it is made of polystyrene, polyacrylonitrile or mixed polymers.