WO1996025185A1

WO1996025185A1 - Artificial vessel systems and process for producing them

Info

Publication number: WO1996025185A1
Application number: PCT/EP1996/000608
Authority: WO
Inventors: Axel Haverich; Gustav Steinhoff; Sörge Kelm; Knut Peer Walluscheck
Original assignee: Axel Haverich; Gustav Steinhoff; Kelm Soerge; Knut Peer Walluscheck
Priority date: 1995-02-15
Filing date: 1996-02-13
Publication date: 1996-08-22
Also published as: DE19505070C2; DE19505070A1

Abstract

The invention relates to an artificial blood vessel system with an internal surface coating. As against prior art systems, the artificial blood vessel system of the invention has increased cell adhesion and retention, especially of endothelial cells. The invention also relates to a process for producing an artificial vessel system in which a two-component coating is applied to the inner surface of the vessels in two steps. The first component is macromolecular and contains more than one primary amino group. The preferred macromolecular component is poly-L-lysine hydrobromide. The second component, which is added in process step b), contains at least two active groups, including at least one aldehyde group. It is of special advantage here to use glutaric dialdehyde. The third component comprises an oligo saccharide, oligo peptide or oligo protein containing an arginine-glycine asparagine (RGD) sequence which especially increases the fixing of endothelial cells.

Description

Artificial vascular systems and processes for their manufacture

The invention relates to an artificial blood vessel system, on the precoated surfaces of which a substance with cell adhesion is applied.

The invention further relates to a method for producing the artificial vascular system, in which the inner surface of the vascular system is precoated and, in a further process step, a substance is applied which is bound by certain cell adhesion receptors.

The chemical and physical composition of artificial vascular systems is constantly being further developed and improved, since autologous vascular systems as a replacement for natural vascular systems are only available to a limited extent. In the vascular systems, the inner surface, which activates numerous mechanical and metabolic properties, is of particular importance. This is particularly true for artificial blood vessel systems, because the inner surface of these vascular systems is crucial for the trouble-free blood flow and blood clotting.

For example, the use of untreated, synthetic vascular grafts, which are used as a blood vessel replacement in particular in cardiac and vascular surgery, can cause the vascular systems in patients to become occluded. can also lead to lethal consequences, such as a stroke.

In order to avoid such disturbances in artificial vascular systems, the inner surface must be pretreated accordingly. In artificial vascular prostheses, for example, endothelial cells (EC) are introduced into the interior of the system. The accumulation of a natural endothelial cell layer on the inner walls of the artificial vascular systems reduces the risk of thrombosis and thus the rate of occlusion of the artificial prosthesis.

A major disadvantage, however, is that the adhesion of cells, in particular endothelial cells, to the inner walls of the synthetic materials is very low. Endothelial cell colonization on the inner walls is promoted, however, if a substance is applied there beforehand which increases the desired cell adhesion. These substances are then recognized and bound by the receptors of the cells that are to be colonized. With regard to the endothelial cell adhesion in artificial blood vessels, various methods are known which improve this adhesion to the inner walls of the vascular system. The inner surface of these synthetic blood vessel systems is e.g. precoated using various matrix proteins.

Plasma proteins such as collagen and laminin, which improve adhesion of the endothelial cells, are known in particular as precoating substances. Fibronectin, which is applied to PTFE surfaces, is considered to be the main success substance for cell adhesion.

Sank et al. disclose a process in which PTFE grafts are initially either with plasma proteins such as gelatin, laminin, fibronectin and collagen or with peptides that are RGD- Sequence included, coated directly. This is followed by colonization with endothelial cells (Sank et al., Am J Surg 1992, No. 164, pages 199-204).

European patent application EP 0 531 547 AI describes an artificial blood vessel system which is coated with a plasma protein which has endothelial cell adhesion. The proteins used are collagen, gelatin, laminin and fibronectin. The plasma protein is covalently bound to the inner walls of the synthetic material of the vascular system via functional hydroxide, carboxyl-epoxy or amino groups.

Endothelial cells can then be colonized on these inner walls pre-coated in this way.

However, some of these methods known from the prior art have considerable disadvantages.

For example, a complicated and long-lasting precoating, which takes place before cell colonization, stands in the way of a wide range of clinical applications. A possible transmission of virus infections, which can occur, for example, by pre-coating with human plasma components such as fibrin glue, should also be avoided. Can be ^{"Furthermore,} an intravascular application of plasma proteins thrombin and fibrin is thrombogenic highly and possibly promotes coagulation, an endothelial cell monolayer not provided immediately after the endothelial colonization obtained. The known methods are mainly used to coat surfaces of polytetrafluoroethylene (PTFE). The Coating of dacron and polyurethane surfaces was also carried out, albeit less frequently.

The adhesion of endothelial cells to fibronectin and also to laminin and tenascin is due to an amino acid sequence. lead, which is contained in these plasma proteins. This substance is a peptide which contains an arginine-glycine-asparagine (RGD) amino acid sequence. A substance which contains at least one arginine-glycine-asparagine amino acid sequence is called RGD-containing substance in the following. This sequence is recognized by integrin receptors of the endothelial cell and other cells (Takemoto et al., ASAIO Transactions 1989; No. 35, pages 354-356).

Compared to the naturally occurring sequences in plasma proteins, however, cell adhesion is increased by synthetic peptides containing RGD. This is attributed to the different structures of the synthetic peptides compared to the natural sequences. In addition, synthetic RGD-containing peptides for cell receptors can be more selective than peptides that correspond to the natural sequences of extracellular matrix proteins. Substances which contain an RGD sequence are recognized and bound by various cell receptors, in particular endothelial cell receptors.

If the RGD-containing substance is brought directly onto the synthetic inner surface of the vessel, the RGD-containing substance is only randomly, unspecifically and incompletely bound to the synthetic material. This has the consequence that the density of the RGD sequences on the inner walls of the vascular system is very low. This low density in turn only results in a low cell population. A trouble-free flow through the artificial vascular system cannot be guaranteed. The direct coating of the surface of the vessel with an RGD-containing substance is therefore not to be regarded as optimal, both for cell adhesion and retention and for the resulting metabolic properties of the artificial vascular system.

The object of the present invention is to provide an artificial blood vessel system in which the Adhesion and retention of cells, in particular of endothelial cells, is increased and improved. The use of such artificial blood vessel systems results in an uninterrupted blood flow, which reduces the risk of thrombosis and thus reduces the occlusion rate of the artificial vascular prosthesis.

It is also an object of the present invention to provide a method for producing an artificial vascular system which leads to a significant increase in the adhesion and retention of cells on the inner wall of the vascular systems and thus to an improvement in the metabolic properties of the artificial vascular systems .

The features of the independent claims serve to solve this problem.

Advantageous configurations are defined in the subclaims.

The artificial blood vessel system is made of a synthetic material such as polytetrafluoroethylene (PTFE), polyurethane, silicone and the like. The artificial blood vessel systems according to the invention contain an inner precoated surface to which a substance with cell adhesion properties is applied. The coating of the inner surface comprises two components which are reacted with one another, namely a first macromolecular component with more than one primary amino group, and a second component which has at least two reactive groups, of which at least one aldehyde group. The use of a poly-lysine hydrohalide, preferably a poly-L-hydrohalide and in particular a poly-L-lysine hydrobromide, is particularly suitable. Glutaraldehyde is preferably used as the second component. The substance applied to the pre-coated inner surface which promotes cell adhesion is an oligosaccharide, peptide or protein. These substances have at least one RGD Sequence on. Cell receptors, in particular endothelial cell receptors, are bound via this RGD sequence.

The artificial blood vessels according to the invention bring about an increased cell colonization and retention compared to the artificial blood vessel systems known from the prior art due to the high density of the adhesion-promoting substances. As a result, the blood flow and blood clotting run smoothly. Adverse effects, e.g. occlusion of the artificial blood vessel systems are effectively avoided.

Because of the increased cell adhesion and retention, the artificial blood vessel system according to the invention is particularly suitable as a replacement for natural arterial vascular systems. The artificial vascular systems according to the invention are particularly suitable in cardiac and vascular surgery as a replacement for natural vascular systems.

These artificial blood vessel systems can be produced, for example, using the inventive method - as described below.

The method according to the invention for producing an artificial vascular system consisting of a synthetic material in which the inner surface is precoated and subsequently a substance is applied which is recognized and bound by cell adhesion receptors comprises the following method steps:

a) In a first process step, the artificial vascular system is coated with a macromolecular component which must have more than one primary amino group.

b) In a second process step, the primary amino group-containing, macromolecular component with a implemented second component, which contains at least two reactive groups, including at least one aldehyde group.

c) ^'The b and by the steps a)) pre-coated, artificial Liehe vascular system is reacted with a substance which is recognized by specific cellular receptors and bound.

The artificial vascular system according to the invention mainly consists of a synthetic material, such as polytetrafluoroethylene (PTFE), polyurethane, silicone and the like. In process step a) the inner wall of the artificial vascular system is coated with the first macromolecular component. An important aspect of the inventive method is that the primary amino groups of the macromolecular component of process step a) are arranged in side chains. Poly-lysine hydrohalide, in particular poly-L-lysine hydrohalide, is preferably used as the macromolecular component. The use of poly-L-lysine hydrobromide is particularly advantageous.

In process step b), this macromolecular component is reacted with a second component, the second component being used in a molar amount which is suitable for functionalizing all the primary amino groups of the first component. The use of glutardialdehyde is particularly advantageous here. The artificial vascular system is coated on the inside by process steps a) and b). After the inner surface has been precoated, a peptide, saccharide or protein is optionally applied to the coated surface in process step c), which causes cell adhesion and retention of the desired cells. This substance can be an oligopeptide, saccharide or protein. It must contain at least one reactive group that can react with the derivatized coating material, e.g. primary amino groups.

Process steps a) and b) lead to a coating the artificial inner walls of the vessel, which consists of two components. It has been shown here that the second component of the coating, which contains at least two reactive groups and at least one aldehyde group thereof, is particularly important for the invention. This component acts as a spacer between the inner surface of the vascular system and the cell receptors of the cells that are located on the surface. The two-component coating effects a targeted orientation and binding of the substances that cause cell adhesion; This is because the primary NH ₂ groups of the first component, which are regularly spaced from one another and are spaced apart from one another, are used to selectively bind the second component, which is preferably a glutardialdehyde. The glutardialdehyde is bound via the first aldehyde functions to the primary amino groups of the artificial vascular system precoated with poly-lysine hydrohalide, in particular with poly-L-lysine hydrobromide. The pre-coated vascular system is then reacted with a substance that has specific adhesion to the cells that are to be colonized. Oligosaccharides, peptides or proteins, which contain, for example, an RGD sequence, are particularly suitable for the adhesion and retention of endothelial cells and other cells. The freely available aldehyde functions of the two-component coating, which can be provided in particular by a derivatized polyysine, bind, for example, primary amino groups of the substances having specific cell adhesion used. The coating mechanism of the method according to the invention is shown in FIGS. 1 a) to c).

Because of the method according to the invention, there is no random and uncoordinated binding of the substances promoting cell adhesion, in particular the RGD peptides or proteins. The binding of these substances to the synthetic inner walls is deliberately arranged at regular intervals Aldehyde functions of the second coating components are achieved. The resulting greater density and stability of the biologically active peptides or proteins leads at the same time to an increase in cell colonization and cell retention. The increased cell colonization on the inner walls of the vessel counteracts a closure of the vascular system. The metabolic properties of the artificial vascular systems are significantly improved.

The following exemplary embodiment explains the invention without, however, restricting it.

Embodiment

1. Production of the artificial vascular system

In step a), the PTFE graft (n = 5) is filled with 40 μm / ml poly-L-lysine hydrobromide (Sigma GmbH, Deisenhofen, Germany) in PBS (phosphate-buffered saline) and incubated at room temperature for 24 hours to enable adsorption of the polypeptide on the PTFE material. After rinsing the transplant with PBS, a solution of 0.2% glutardialdehyde (Sigma GmbH, Deisenhofen, FRG) in PBS is instilled into the grafts in process step b) and left to stand for 10 minutes. The graft is rinsed again with PBS. In step c), the graft pre-coated in this way is completely filled with 100 μg / ml of a synthetic peptide which promotes the adhesion of endothelial cells in PBS (Gly-Arg-Gly-Asp-Ser-Pro-Lys) (Gibco, Life Technologies Inc. , Gaithersburg, USA), which contains the RGD sequence, filled and left for 60 minutes. After removal of the peptide solution, a solution with 1% bovine serum albumin (Sigma Chemical Co., St. Louis, USA) in PBS is introduced into the grafts for 30 minutes in order to occupy possible unbound aldehyde sites. The graft is then washed with PBS.

2. Endothelial cell colonization

An endothelial cell culture is created on the RGD-peptide-coated vascular system, which is obtained from a surface vein, for example from an adult's saphene (AHSVEC). Endothelial cells from the second to third culture passages are treated with trypsin, centrifuged and resuspended in the complete nutrient medium. An aliquot is used for cell counting in a hemocytometer and the cell suspension is adjusted to a cell density of 1.2 x 10 ⁵ endothelial cells / cm ² in order to cover the available prosthesis surface of 6.3 cm ² . The graft is filled with the endothelial cell suspension by means of a syringe, closed at both ends and incubated for 30 minutes in a humidified incubator in an atmosphere of 5% carbon dioxide / 95% air at a temperature of 37 ° C. After 15 minutes, the graft segments are rotated once through 180 °. At the end of the colonization process, the grafts are rinsed with the nutrient medium.

Comparative tests

A comparison of the endothelial cell adhesion and retention on uncoated, vascular systems coated with plasma proteins, coated according to the invention and coated with polylysine / glutardialdehyde (without RGD) was carried out.

Group 1 represents an uncoated PTFE vascular system. A PTFE graft coated with human fibronectin is referred to as Group 2. Comparative groups 1 and 2 were produced by the processes known from the prior art.

Group 3 is a precoated blood vessel system according to the invention, which is produced as described in the exemplary embodiment has been .

Group 4 is a pre-coated blood vessel system which was produced in accordance with process steps a) and b) according to the invention. However, there is no RGD-containing substance with cell adhesion.

In the experiments to determine the endothelial cell adhesion and retention on the inner walls of the vessel before and after perfusion of the PTFE vascular systems of groups 1, 2, 3 and 4, endothelial cells were populated. At the end of the colonization process, the grafts of groups 1, 2, 3 and 4 were briefly rinsed with nutrient medium. Then a Luer connector was removed and a defined segment with a length of 1 cm from groups 1, 2, 3 and 4 was prepared for an examination in a scanning electron microscope (SEM).

The Luer connectors were then replaced and the grafts placed in an artificial flow circuit in order to determine the resistance to shear stress and the cell retention of an applied endothelial cell seed on the PTFE surfaces (see FIG. 2). A pulsating flow was performed using a roller pump (Medax, Kiel, FRG) of a cardiotomy container, equipped with a perfusion medium filter and an air bubble filter (Sorin Biomedica, Saluggia, Italy) and an extracorporeal standard perfusion tube (Jostra, Hirrlingen, FRG) in one closed, sterile system. The PTFE grafts provided with a cell culture, which were enclosed in a specially developed glass tube, were integrated into the circuit via the previously inserted Luer connectors. The system was filled with 500 ml of M-199 nutrient medium, 10% human serum and antibiotics. No endothelial cell growth factors were added to the perfusion medium and the temperature was raised to 37 while performing with a water bath

O'Cf kept. Before using the system, the ^" Perfusion medium incubated at 37 "C in an atmosphere of 5% CO ₂ /95% room air. The pressure was adjusted and kept constant at 35/5 mm mercury (Hg), which gave 30 pulsations per minute. The pressure was measured with a membrane The transducer and a pressure monitor (Hewlett Packard, Andover, USA). The speed of the flow circuit was 100 ml / minute, which was maintained for one hour. After perfusion, both Luer connectors were removed from the respective transplants in groups 1 and 2 , 3 and 4 removed, a specific graft segment cut out and prepared for scanning electron microscopy.

The following steps were taken to prepare the removed graft segments for scanning electron microscopy (SEM):

1 cm long samples of flowed grafts containing the cell seeds are examined by means of scanning electron microscopy with regard to their quantification and morphology.

Immediately after preparation from the artificial vascular systems, the samples are fixed in 3.5% glutaraldehyde for at least 4 hours and rinsed with phosphate buffer solution. This is followed by post-fixation for 2 hours in 2% osmium tetroxide in buffer solution. After dehydration using various ethanol solutions, the samples are dried to their critical point with liquid CO ₂ , sputter-coated in a vacuum evaporator with gold / palladium, and with a scanning electron microscope (Philips XL 20, Kassel, Germany), which has an acceleration voltage of 25 kV is operated, examined.

Results of the comparison tests

A summary of the results of the scanning electron microscopy is shown in FIGS. 3 to 5. The results of the comparative tests for groups 1, 2 and 3 show that the endothelial cell adhesion and retention on PTFE-coated vascular prostheses according to the invention after colonization (FIGS. 3a, 4a, 5a) and perfusion (FIGS. 3b, 4b , 5b) are significantly increased and improved in an artificial flow circuit compared to the uncoated and coated PTFE vascular prostheses known from the prior art.

Cell adhesion and retention on the grafts before and after perfusion

Group 1: In uncoated PTFE vascular systems, 30 minutes after cell colonization of 1.2 × 10 ⁵ AHSVEC / cm ^2, 14.9% ± 3.1% of the area was covered with endothelial cells. After the perfusion, the endothelial cell adhesion was 2.0% ± 1.0%. Cell retention was 13.9% ± 7.9% (see Figures 6 and 7).

Group 2: The pre-coating of PTFE grafts with human fibronectin resulted in endothelial cell adhesion after endothelial cell colonization of 26.0% ± 3.3%. After perfusion in the artificial circuit, the endothelial cell adhesion was 11.8% ± 1.6%. The calculated cell retention was 45.5% ± 2.1%. Both endothelial cell adhesion and retention were considerably higher than in group 1 (see FIGS. 6 and 7).

Group 3: Endothelial cell adhesion of 30.6% ± 2.1% was observed in the PTFE vascular systems pretreated according to the invention. Perfusion of the PTFE grafts resulted in endothelial cell adhesion of 19.3% ± 2.8%. Endothelial cell retention was 62.9% + 7.5%. Compared to group 1 and group 2 (see FIGS. 6 and 7), there was a further significant increase in endothelial cell adhesion and retention. This better result is primarily due to the precoating technique according to the invention. In the von Sank ' et al. The RGD peptides are applied directly to the PTFE material without pre-coating. Further subordinate differences consist in the fact that Sank et al. have used another RGD peptide in a lower concentration using PTFE patch instead of tubular prostheses. The lower peptide concentration and the use of a PTFE patch also lead to that of Sank et al. Result found that endothelial cell adhesion on RGD piptide coated PTFE is slightly lower than on fibronectin coated PTFE. The results relating to the cell adhesion of groups 1 and 2 of the comparative experiments described are in contrast to this.

Group 4: The precoating of PTFE grafts according to the process steps according to the invention with polylysine / glutardialdehyde (however, there is no RGD-containing substance with cell adhesion) resulted in endothelial cell adhesion after endothelial cell colonization of 10.5% ± 1.1%. After perfusion in the artificial circuit, the endothelial cell adhesion was 0.7% ± 0.2%. The calculated cell retention was 6.6% ± 1.5%. Both endothelial cell adhesion and retention were considerably lower compared to group 3 (see FIGS. 6 and 7).

The improved results with regard to cell adhesion and cell retention of the artificial vascular system according to the invention can be attributed to the precoating method of the invention. In the method according to the invention, two intermediate steps are used to connect the cell adhesion-demanding substance to the inner wall of the vascular system surface. This leads to a strong biochemical bond of the adhesion-promoting substance with the graft and an increased resistance to shear stress. The substance promoting adhesion is bound to the artificial inner walls via the aldehyde group of the second component that is still available. Proteins and peptides with at least one RGD sequence bound to the second coating component, for example, via primary amino groups.

A comparison of groups 1, 2, 3 and 4 shows that group 3, which corresponds to the artificial blood vessel systems according to the invention, has a higher resistance to shear stress. This increased resilience was determined based on the extent of endothelial cell adhesion and retention after perfusion in the artificial circuit. While 19.3% ± 2.8% endothelial cell adhesion was found after perfusion on the transplants according to the invention coated with RGD peptides, this was only 11.8% ± 1.6% in the case of fibronectin-coated transplants. . The endothelial cell adhesion after perfusion was 2.0% ± 1.0% on uncoated grafts. On grafts coated exclusively with polylysine / glutardialdehyde, the endothelial cell adhesion after perfusion was only 0.7% ± 0.2%.

In the case of uncoated grafts, only 13.9% ± 7.9% of the originally adhering endothelial cells were present after a one-hour shear stress. An endothelial cell retention of 45.5% ± 2.1% was measured on fibronectin-coated grafts. The endothelial cell retention was 6.6% + 1.5% on grafts coated exclusively with polylysine / glutardialdehyde. By far the highest endothelial cell retention of 62.9% ± 7.5% was again found in the case of PTFE grafts which were precoated in accordance with the invention.

Compared to the prior art, the cell adhesion and retention of endothelial cells on vascular systems coated according to the invention is considerably increased. Due to their improved metabolic properties, the coated vascular systems according to the invention reduce or avoid disturbances and side effects which arise, for example, from contact of the circulating blood stream with the plastic material. The improved metabolic properties compared to the prior art are due to an increased density of the biologically active substances that promote cell adhesion. The inventive vascular systems replace the natural vessels in the cardiovascular system, particularly in cardiac and vascular surgery.

Description of the figures

Figure 1: Schematic representation of biochemical reactions in the inventive method. Glutardialdehyde binds via aldehyde functions to the primary amino group of polylysine, with which the PTFE material is precoated (a). The available aldehyde functions of the derivatized polylysine can bind primary amino groups of the synthetic, adhesion-promoting RGD peptides (b). Through the integrin family of cell matrix receptors, endothelial cells interact with the RGD sequence bound to the inner wall of the vascular system and adhere to the PTFE graft (c).

Figure 2: Schematic representation of the artificial circuit. Cardiotomy container (1) with air bubble filter (2), perfusion medium filter (3), water bath (4), extracorporeal perfusion tube (5), membrane measuring transducer (6), pressure and temperature monitor (7), glass tube holding the graft enclosed, with inlet and outlet for the surrounding medium (8), PTFE-graft (9) populated with cells, temperature transducer (10), roller pump (11), flow nutrient medium (12), inlet for C0 ₂ setting (13 ), Inlet for nutrient medium (14). The arrows point in the direction of the river.

FIG. 3: scanning electron micrography of an uncoated PTFE graft after a 30-minute endothelial cell colonization (1.2 × 10 ⁵ EC / cm ² ) (FIG. 3 a) and after a one-hour perfusion in a flow circuit (100 ml / min .) (Fig. 3 b). Original magnification x 618. FIG. 4: scanning electron micrography of a fibronectin-coated PTFE graft after 30 minutes of endothelial cell colonization (1.2 × 10 ⁵ EC / cm ² ) (FIG. 4 a) and after an hour's perfusion in the flow circuit (100 ml / min.) (Fig. 4 b). Original magnification x 618.

FIG. 5: scanning electron micrography of a PTFE graft which is coated with adhesion-demanding RGD peptide, 30 minutes after endothelial cell colonization (1.2 × 10 ⁵ EC / cm ² ) (FIG. 5 a) and after one hour of perfusion in the flow circuit (100 ml / min.) (Fig. 5 b). Original magnification x 618.

FIG. 6: Comparison of the endothelial cell adhesion on uncoated, coated with fibronectin (HFN), with polylysine / glutardialdehyde (PL / GA; without RGD) and with adhesion-demanding

RGD peptide (RGD) coated PTFE grafts. The area covered with EC (%) 30 minutes after endothelial cell colonization

(1.2 x 10 ⁵ EC / cm ² ) and after perfusion in a flow cycle

(100 ml / min.). Calculated standard deviation in brackets.

FIG. 7: Comparison of the EC retention (adherent cells after per fusion / original adherent cells after colonization) on uncoated, coated with fibronectin (HFN), with polylysine / glutardialdehyde (PL / GA; without RGD) and with adhesion-promoting RGD peptide (RGD) coated PTFE grafts. Calculated standard deviation in brackets.

Claims

claims

1. Artificial blood vessel system comprising an inner coated surface to which a substance with cell adhesion is applied, characterized in that the inner pre-coated surface contains two components which have been reacted with one another, namely a macromolecular component containing more than one primary amino group and a component which has at least two reactive groups, including at least one aldehyde group, and the substance with cell adhesion is an oligosaccharide, peptide, or protein, in particular a peptide, saccharide or protein with at least one RGD (arginine-glycine-asparagine) Amino¬ acid sequence.

2. Artificial blood vessel system according to claim 1, characterized in that the artificial vascular system consists of a synthetic material such as polytetrafluoroethylene (PTFE), polyurethane, silicone and the like.

3. Artificial blood vessel system according to claim 1, characterized in that the protein, saccharide or peptide containing at least one RGD (arginine-glycine-asparagine) amino acid sequence is bound by cell receptors, in particular endothelial cell receptors.

4. Artificial blood vessel system according to claim 1, characterized in that the primary amino groups of the first macromolecular component of the coated inner surface are arranged in side chains.

5. Artificial blood vessel system according to one of claims 1 and 4, characterized in that in the surface coating the first macromolecular component is poly-lysine hydrohalide, preferably a poly-L-lysine hydrohalide and in particular poly-L-hydrobromide.

6. Artificial blood vessel system according to claim 1, characterized in that in the surface coating the second component is glutardialdehyde.

7. Process for the production of an artificial vascular system, consisting of a synthetic material, by pre-coating the inner surface and subsequently applying a substance that is recognized and bound by cell adhesion receptors.

characterized by the following process steps:

a) the artificial vascular system is coated with a first macromolecular component which contains more than one primary amino group

b) the primary amino group-containing macromolecular component is reacted with a second component which contains at least two reactive groups, including at least one aldehyde group c) the artificial vascular system precoated by steps a) and b) is coated with an oligosaccharide, peptide or protein, in particular a peptide, saccharide or protein which has at least one RGD

(Arginine-glycine-asparagine) amino acid sequence has been implemented.

8. The method according to claim 7, characterized in that the artificial vascular system consists of a synthetic material such as polytetrafluoroethylene (PTFE), polyurethane, silicone and the like.

9. The method according to claim 7, characterized in that the primary amino groups of the macromolecular component of step a) are arranged in side chains.

10. The method according to claim 9, characterized in that the macromolecular component is a poly-lysine hydrohalide, preferably a poly-L-lysine hydrohalide and in particular poly-L-lysine hydrobromide.

11. The method according to claim 7, characterized in that the macromolecular component is reacted with glutardialdehyde as the second component in process step b), the second component being used in a molar amount which is suitable for all NH ₂ groups of the first Functionalize component.

12. The method according to claim 7, characterized in that the protein, saccharide or peptide containing at least one RGD sequence is bound by cell receptors, in particular by endothelial cell receptors.