DE102022128813A1 - Anti-adhesive polymer coatings for short-term implants - Google Patents

Abstract

The present invention relates to hydrophilic (co)polymers with chemically reactive (covalently) bound anchor groups and/or crosslinking molecules, which allow attachment to the underlying substrate or linking of these polymers to form networks. The invention further relates to hydrogels and coatings, in particular implant coatings, which comprise the polymers according to the invention, as well as medical devices, such as implants, which are coated with a coating according to the invention.

Description

Field of the invention

The present invention relates to hydrophilic (co)polymers with chemically reactive (covalent) bound anchor groups and/or crosslinking molecules, which allow attachment to the underlying substrate or linking of these polymers to form networks. Coating short-term implants with such water-swellable polymer networks (hydrogels) prevents adhesion of cells and tissue to the surface (antifouling) without causing cytotoxicity, and at the same time achieves an intrinsic antibacterial effect without the need to add additional antibiotics or bactericides. Since the surrounding tissue cannot adhere to an anti-adhesive coated implant, it is not damaged when the implant is removed. In addition, the intrinsic antibacterial effect of certain coatings prevents an infection that often occurs during implantation.

The described coatings can serve as modifications for commercially available, medically approved implants for the purpose of simplifying the removal of the short-term implant after the end of the wearing period and preventing complications during implantation and wearing time.

Background of the invention

Modern implants in trauma surgery and orthopedics, which are implanted in the patient for a maximum of 12 months (short-term implants), are widely used to provide temporary support for the bone structure, for example after an acute accident. They are often made of titanium and must be removed in the event of complications, but at the latest after the end of the period of use.

The requirements for such short-term implants are contrary to those for long-term implants, which remain in the patient's body for several years or even decades (e.g. hip or knee implants). With long-term implants, complete integration of the implant into the body's own tissue is desired in order to achieve a permanent and stable support function. In contrast, for short-term implants it is desirable that the implants do not bond with the surrounding tissue in order to prevent ruptures during removal. Reasons for the need to remove an implant can be adhesions of surrounding tissue to the surface. Titanium implants form such adhesions more frequently than steel implants, for example. The adhesion of tendons to an implant plate, especially to a titanium surface, can lead to restricted movement and even stiffening of joints, for example in the hand and wrist area.

If nerves adhere to the surface of the plate, as can happen, for example, during plate osteosynthesis of the humeral shaft, this makes surgical removal of the plate much more difficult and significantly increases the risk of permanent nerve damage. Such avoidable complications are often associated with greater pain, prolonged healing processes and increased psychological stress for the patient. In addition, every implantation is fundamentally associated with an increased risk of infection. In the event of an infection, the result is usually the administration of antibiotics and/or an implant replacement with a longer hospital stay, which increases the physical and psychological stress for the patient and the costs for the health system, while at the same time straining the capacities of medical institutions. An anti-adhesive coating could both reduce complications after implantation and minimize the risks of implant removal.

At present, no relevant patented systems are known for anti-adhesive coatings of short-term implants. In contrast to surface modifications of short-term implants, some coatings for long-term implants to improve their properties are already known. Documented coatings consist, for example, of (click-functionalized) polymers [1-3] or hydroxyapatite and other calcium compounds. [4,5] These usually have an osteoconductive effect in order to enable good integration of the implant into the surrounding tissue. This means that these types of coating do not have an anti-adhesive effect, but, on the contrary, promote cell adhesion to the implant.

Other methods of implant coating require special processes, such as plasma treatments, laser deposition processes, or anodization, which in turn require more complex equipment and thus also entail increased costs. In addition, such methods are not or only partially suitable for more complex geometries.

In addition, there are already publications on implant modifications that produce an antibacterial effect. The majority of these coatings are based on antibiotic, bactericidal, silver or copper-containing coatings. [5,6] In this case, antibiotics are often released from the implant to the surrounding tissue over a limited period of time in order to prevent infection. This release of antibiotics can in turn lead to resistance or allergic reactions. Metal ion-based bactericides, on the other hand, can lead to local toxicity.

In addition to metal implants, bioresorbable implants are considered promising short-term implants, as they do not require removal after the period of wear has ended. However, degradable implants have different physical properties to metals, such as lower ductility and tensile strength. In particular, these implants do not offer consistently strong stabilization of the bone structure over their entire implementation period, but lose stability during the decomposition process. [7,8] For this reason, bioresorbable implants are only suitable to a limited extent for corresponding clinical questions in which constant robustness of the implant is required. The degradation products of the bioresorbable implant, which can be present locally in high concentrations, must also not be cytotoxic, as they could otherwise lead to undesirable reactions. The body must be able to metabolize or degrade these products. [8]

Accordingly, the object of the present invention is to provide novel and advantageous polymer coatings which, among other things, allow the use of implants as short-term implants.

Summary of the invention

The underlying problem is solved by providing a (co)polymer according to the invention.

The polymer chains of the present invention described here and on which the hydrogel is based consist of hydrophilic main monomers and crosslinking monomers, some with antibacterial structural motifs, and/or dedicated anchor groups for the corresponding implant substrate. By carefully selecting these modularly combinable monomers, it is possible to produce biocompatible, antiadhesive and antibacterial polymer networks at the same time.

For this invention, the linking of the polymer chains with benzophenone derivative-based crosslinking monomers by irradiation with UV light is a particular advantage. Such photochemically activated network formation can produce extremely thin (in the sub-micrometer range), uniform and covalently bonded coatings on the implant surface. Such light-induced crosslinking of the polymer coating can also be carried out with more complex implant geometries. In addition, the UV irradiation step allows simultaneous sterilization of the implant. By introducing an antibacterial structural motif (e.g. a quaternary ammonium group, which has an antibacterial effect due to its ionic structure) into the polymer chains for the coatings, the risk of infection for the patient during surgery can be reduced in order to prevent impairment of wound healing and tissue regeneration. In the invention described here, bactericidal active ingredients that must be added to the implant are not required, since the antibacterial effect is ensured solely by the intrinsic nature of the antiadhesive hydrogel. An undesirable free migration of such unbound active substances into the surrounding environment (tissue, bones, organs, etc.) is thus avoided.

In addition, the polymer network coating is extremely hard and mechanically stable when dry and only swells into a soft, anti-adhesive and antibacterial hydrogel after implantation in the body. In addition, the invention presented here does not require any technically complex processes and only consists of incubating the implant substrate (single-layer system) and/or applying a polymer solution to the implant (sandwich structure) and irradiating it with a UV lamp after drying.

These are far-reaching innovations in the coating development of implants.

1. 1. Polymer aufweisend eine Struktur der allgemeinen Formel (I)
   
   wobei A₁ -H oder -CH₃ ist; A₂ -H oder -CH₃ ist; A₃ -H oder -CH₃ ist; A₄ -H oder -CH₃ ist; R₁, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus
   
   
   
   R₂, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus
   
   wobei jeder „Spacer“ jeweils unabhängig voneinander ausgewählt ist aus der Gruppe bestehend aus linearen oder verzweigten Alkylketten und linearen oder verzweigten Ethylen- oder Propylenoxidketten, vorzugweise unabhängig voneinander ausgewählt aus linearen oder verzweigen C_1-20-Alkylketten; Rx, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; und Ry, jeweils unabhängig voneinander, -OH, Halogen (Br, Cl, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; R₃, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus
   
   
   wobei n₃, n₄, n₅, n₆ und n₇ jeweils unabhängig voneinander 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 oder 18 ist; R₄, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus
   
   Y ein Fragment A eines Kettenübertragungsreagenzes oder eine Endgruppe ist; und Z ein Fragment B des Kettenübertragungsreagenzes oder eine Endgruppe ist.
2. 2. Polymer gemäß Ausführungsform 1, wobei R₁, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus
   
3. 3. Polymer gemäß Ausführungsform 1, wobei R₁, für jede Wiederholungseinheit,
   
   ist.
4. 4. Polymer gemäß Ausführungsform 1, wobei R₁, für jede Wiederholungseinheit,
   
   ist.
5. 5. Polymer gemäß einer der Ausführungsformen 1 bis 4, wobei A₁ -H ist.
6. 6. Polymer gemäß einer der Ausführungsformen 1 bis 4, wobei A₁ -CH₃ ist.
7. 7. Polymer gemäß einer der Ausführungsformen 1 bis 6, wobei R₂, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus
   
   wobei n₁ und n₂ jeweils unabhängig voneinander 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 oder 20 ist; R_x, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; und R_y, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist.
8. 8. Polymer gemäß einer der Ausführungsformen 1 bis 6, wobei R₂, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus
   
9. 9. Polymer gemäß einer der Ausführungsformen 1 bis 6, wobei R₂, für jede Wiederholungseinheit,
   
   ist.
10. 10. Polymer gemäß einer der Ausführungsformen 1 bis 6, wobei R₂, für jede Wiederholungseinheit,
    
    ist, wobei jeder „Spacer“ jeweils unabhängig voneinander ausgewählt ist aus der Gruppe bestehend aus linearen oder verzweigten Alkylketten und linearen oder verzweigten Ethylen- oder Propylenoxidketten, vorzugweise unabhängig voneinander ausgewählt aus linearen oder verzweigen C_1-20-Alkylketten; R_x, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; und R_y, jeweils unabhängig voneinander, -OH, Halogen (Br, Cl, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist.
11. 11. Polymer gemäß einer der Ausführungsformen 1 bis 6, wobei R₂, für jede Wiederholungseinheit,
    
    ist, wobei n₁ und n₂ jeweils unabhängig voneinander 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 oder 20 ist; R_x, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; und R_y, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist.
12. 12. Polymer gemäß einer der Ausführungsformen 1 bis 6, wobei R₂, für jede Wiederholungseinheit,
    
    ist.
13. 13. Polymer gemäß einer der Ausführungsformen 1 bis 12, wobei A₂-H ist.
14. 14. Polymer gemäß einer der Ausführungsformen 1 bis 12, wobei A₂-CH₃ ist.
15. 15. Polymer gemäß einer der Ausführungsformen 1 bis 14, wobei R₃, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus
    
    wobei n₃, n₄, n₅, n₆ und n₇ jeweils unabhängig voneinander 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 oder 18 ist.
16. 16. Polymer gemäß einer der Ausführungsformen 1 bis 14, wobei R₃, für jede Wiederholungseinheit,
    
    ist, wobei n₃ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 oder 18 ist.
17. 17. Polymer gemäß einer der Ausführungsformen 1 bis 14, wobei R₃, für jede Wiederholungseinheit,
    
    ist.
18. 18. Polymer gemäß einer der Ausführungsformen 1 bis 14, wobei R₃, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus
    
19. 19. Polymer gemäß einer der Ausführungsformen 1 bis 18, wobei A₃ -H ist.
20. 20. Polymer gemäß einer der Ausführungsformen 1 bis 18, wobei A₃ -CH₃ ist.
21. 21. Polymer gemäß einer der Ausführungsformen 1 bis 20, wobei R₄, für jede Wiederholungseinheit,
    
    ist.
22. 22. Polymer gemäß einer der Ausführungsformen 1 bis 20, wobei R₄, für jede Wiederholungseinheit,
    
    ist.
23. 23. Polymer gemäß einer der Ausführungsformen 1 bis 20, wobei R₄, für jede Wiederholungseinheit,
    
    ist.
24. 24. Polymer gemäß einer der Ausführungsformen 1 bis 23, wobei A₄ -H ist.
25. 25. Polymer gemäß einer der Ausführungsformen 1 bis 23, wobei A₄ -CH₃ ist.
26. 26. Polymer gemäß Ausführungsform 1, wobei R₁, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus
    
    R₂, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus
    
    R₃, für jede Wiederholungseinheit,
    
    ist; und R₄, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus
    
27. 27. Polymer gemäß Ausführungsform 26, wobei A₁ -H ist, A₂ -H ist, A₃ -H ist, und A₄ -H ist.
28. 28. Polymer gemäß einer der Ausführungsformen 1 bis 27, wobei Z ein Fragment A eines Kettenübertragungsreagenzes und Y ein Fragment B des Kettenübertragungsreagenzes ist.
29. 29. Polymer gemäß einer der Ausführungsformen 1 bis 28, wobei das Kettenübertragungsreagenz ausgewählt ist aus der Gruppe bestehend aus Dithioester, Trithiocarbonate, Xanthate und Carbamate.
30. 30. Polymer gemäß einer der Ausführungsformen 1 bis 27, wobei Y
    
    ist, und Z
    
    wobei n₈ eine Ganzzahl von 1 bis 24 ist, vorzugsweise eine Ganzzahl von 1 bis 14, weiter bevorzugt eine Ganzzahl von 1 bis 11; am bevorzugtesten 1 oder 11 ist.
31. 31. Polymer gemäß einer der Ausführungsformen 1 bis 27, wobei Y und Z jeweils eine Endgruppe ist.
32. 32. Polymer gemäß einer der Ausführungsformen 1 bis 31, wobei x_[2] >0 bis <1 ist.
33. 33. Polymer gemäß einer der Ausführungsformen 1 bis 32, wobei x_[3] >0 bis <1 ist.
34. 34. Polymer gemäß einer der Ausführungsformen 1 bis 33, wobei x_[4] >0 bis <1 ist.
35. 35. Polymer gemäß einer der Ausführungsformen 1 bis 31, wobei x_[2] 0 ist und x_[3] >0 bis <1 ist; und optional x_[4] >0 bis <1 ist.
36. 36. Polymer gemäß einer der Ausführungsformen 1 bis 31, wobei x_[2] >0 bis <1 ist und x_[3] 0 ist; und optional x_[4] >0 bis <1 ist.
37. 37. Polymer gemäß einer der Ausführungsformen 1 bis 31, wobei x_[2] >0 bis <1 ist und x_[3] >0 bis <1 ist; und optional x_[4] >0 bis <1 ist.
38. 38. Polymer gemäß Ausführungsform 1, ausgewählt aus der Gruppe bestehend aus
    
    
    
    
    
    
    
    
    wobei n eine Ganzzahl von 2 bis 100.000 ist, wie beispielsweise eine Ganzzahl von 50 bis 10.000, z.B. eine Ganzzahl von 100 bis 2.000.
39. 39. Polymer gemäß Ausführungsform 1, ausgewählt aus der Gruppe bestehend aus
    
    
    wobei n eine Ganzzahl von 2 bis 100.000 ist, wie beispielsweise eine Ganzzahl von 50 bis 10.000, z.B. eine Ganzzahl von 100 bis 2.000.
40. 40. Polymer gemäß Ausführungsform 1, ausgewählt aus der Gruppe bestehend aus
    
    
    wobei n eine Ganzzahl von 2 bis 100.000 ist, wie beispielsweise eine Ganzzahl von 50 bis 10.000, z.B. eine Ganzzahl von 100 bis 2.000.
41. 41. Polymer gemäß Ausführungsform 1, ausgewählt aus der Gruppe bestehend aus
    
    wobei n eine Ganzzahl von 2 bis 100.000 ist, wie beispielsweise eine Ganzzahl von 50 bis 10.000, z.B. eine Ganzzahl von 100 bis 2.000.
42. 42. Hydrogel, umfassend ein vernetztes Polymer gemäß einer der Ausführungsformen 1 bis 41.
43. 43. Beschichtung, umfassend mindestens eine Schicht, die ein Polymer gemäß einer der Ausführungsformen 1 bis 41 umfasst.
44. 44. Beschichtung gemäß Ausführungsform 43, umfassend eine erste Schicht, die ein Polymer gemäß Ausführungsform 35 umfasst, und eine zweite Schicht, die ein Polymer gemäß Ausführungsform 36 umfasst.
45. 45. Beschichtung gemäß Ausführungsform 44, wobei die erste und zweite Schichtmiteinander kreuzvernetzt sind.
46. 46. Beschichtung gemäß Ausführungsform 43, die eine Schicht umfasst, die ein Polymer gemäß Ausführungsform 37 umfasst.
47. 47. Metallhaltiges Substrat, dadurch gekennzeichnet, dass mindestens ein Teil seiner Oberfläche mit einer Beschichtung überzogen ist, welche mindestens eine Schicht umfasst, die ein Polymer gemäß einer der Ausführungsformen 1 bis 41 umfasst.
48. 48. Substrat gemäß Ausführungsform 47, wobei die Beschichtung eine Beschichtung gemäß einer der Ausführungsformen 43 bis 46 ist.
49. 49. Substrat gemäß Ausführungsform 47 oder 48, wobei das Substrat aus einem Metall besteht.
50. 50. Substrat gemäß einer der Ausführungsformen 47 bis 49, wobei das Metall ausgewählt ist aus der Gruppe bestehend aus Titan, Titanlegierungen, Aluminium, Aluminiumlegierungen, Zink, Zinklegierungen, Zinn, Zinnlegierungen, Zirkonium, Zirkoniumlegierungen, Tantal, Tantallegierungen, Kobalt, Kobaltlegierungen, Nickel, Nickellegierungen, Kupfer, Kupferlegierungen, Magnesium, Magnesiumlegierungen, Molybdän, Molybdänlegierungen, Niob, Nioblegierungen, Chrom, Chromlegierungen, Eisen, Eisenlegierungen, rostfreier Stahl, und Metalloxiden davon.
51. 51. Substrat gemäß einer der Ausführungsformen 47 bis 51, wobei das Metall ein Metalloxid umfasst.
52. 52. Substrat gemäß Ausführungsform 51, wobei das Metalloxid ausgewählt ist aus der Gruppe bestehend aus TiO₂, AlO₂, ZnO, ZrO₂, ITO, IZO, NiO_x, NiCoO_x, MoO_x Fe₂O₃, und Nb₂O₅.
53. 53. Substrat gemäß einer der Ausführungsformen 51 bis 54, wobei das Substrat Titan, Titanoxid, oder eine Titanlegierung umfasst oder daraus besteht.
54. 54. Substrat gemäß Ausführungsform 53, wobei die Titanlegierung Ti6Al4V oder Ti6AL4V ELI ist.
55. 55. Substrat gemäß Ausführungsform 53, wobei das Titanoxid TiO₂ ist.
56. 56. Vorrichtung, umfassend ein Substrat gemäß einer der Ausführungsformen 47 bis 55.
57. 57. Vorrichtung gemäß Ausführungsform 56, wobei das Substrat mindestens einen Teil der Oberfläche der Vorrichtung bildet.
58. 58. Vorrichtung gemäß Ausführungsform 56 oder 57, wobei die Vorrichtung eine medizinische Vorrichtung ist.
59. 59. Vorrichtung gemäß einer der Ausführungsformen 56 bis 58, wobei die Vorrichtung ein Implantat ist.
60. 60. Verwendung einer Vorrichtung gemäß Ausführungsform 59 als Kurzzeitimplantat.
61. 61. Verfahren zur Beschichtung eines Substrats, umfassend die Schritte
    1. (a) Bereitstellen eines metallhaltigen Substrates, und
    2. (b) In-Kontakt-Bringen des Substrates mit einer Lösung des Polymers gemäß einer der Ausführungsformen 1 bis 41;
    3. (c) gegebenenfalls Trocknen des Substrates; und
    4. (d) gegebenenfalls UV-Bestrahlung.
62. 62. Verfahren zur Beschichtung einer Vorrichtung, umfassend die Schritte
    1. (a) Bereitstellen einer Vorrichtung, umfassend ein metallhaltiges Substrat, und
    2. (b) In-Kontakt-Bringen der Vorrichtung bzw. des Substrates mit einer Lösung des Polymers gemäß einer der Ausführungsformen 1 bis 41;
    3. (c) gegebenenfalls Trocknen des Substrates; und
    4. (d) gegebenenfalls UV-Bestrahlung.
63. 63. Verfahren gemäß Ausführungsform 61 oder 62, wobei Schritt (b) ein erstes In-Kontakt-Bringen der Vorrichtung bzw. des Substrates mit einer Lösung des Polymers gemäß Ausführungsform 39, gefolgt von einem zweiten In-Kontakt-Bringen der Vorrichtung bzw. des Substrates mit einer Lösung des Polymers gemäß Ausführungsform 40 umfasst (Zwei-Schicht-System).
64. 64. Verfahren gemäß Ausführungsform 61 oder 62, wobei Schritt (b) das In-Kontakt-Bringen der Vorrichtung bzw. des Substrates mit einer Lösung des Polymers gemäß Ausführungsform 41 umfasst (Einschichtsystem).
65. 65. Verfahren gemäß einer der Ausführungsformen 61 bis 64, wobei das In-Kontakt-Bringen das Besprühen oder Begießen mit oder Eintauchen in der/die Lösung umfasst.
66. 66. Verwendung des Polymers gemäß einer der Ausführungsform 1 bis 41 als antiadhäsive Beschichtung, vorzugsweise als antiadhäsive Beschichtung auf einer medizinischen Vorrichtung, ferner bevorzugt als antiadhäsive Beschichtung auf einem Implantat.
67. 67. Polymer gemäß einer der Ausführungsformen 1 bis 41 zur Verwendung in einem Verfahren zu Behandlung einer Knochenfraktur in einem Patienten, das Verfahren umfassend
    1. a) Bereitstellen eines Implantats, umfassend ein Substrat, das dadurch gekennzeichnet ist, dass mindestens ein Teil seiner Oberfläche mit einer Beschichtung überzogen ist, welche mindestens eine Schicht umfasst, die ein Polymer gemäß einer der Ausführungsformen 1 bis 45 umfasst; und
    2. b) Einsetzen des Implantats an einer Knochenreparaturstelle oder im Bereich der Knochenfraktur im Patienten.
68. 68. Polymer zur Verwendung gemäß Ausführungsform 67, wobei das Implantat das Implantat der Ausführungsform 59 ist.
69. 69. Monomer aufweisend eine Struktur der allgemeinen Formel (II)
    
    wobei jeder „Spacer“ jeweils unabhängig voneinander ausgewählt ist aus der Gruppe bestehend aus linearen oder verzweigten Alkylketten und linearen oder verzweigten Ethylen- oder Propylenoxidketten, vorzugweise unabhängig voneinander ausgewählt aus linearen oder verzweigen C_1-20-Alkylketten; R_x, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; und R_y, jeweils unabhängig voneinander, -OH, Halogen (Br, Cl, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist.
70. 70. Monomer aufweisend eine Struktur der allgemeinen Formel (IIa)
    
    wobei n₄ und n₂ jeweils unabhängig voneinander 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 oder 20 ist; R_x, jeweils unabhängig voneinander, -H, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. - CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; und R_y, jeweils unabhängig voneinander, -H, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. - CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist.
71. 71. Monomer gemäß Ausführungsform 70, wobei n₁ 1 bis 10 ist.
72. 72. Monomer gemäß Ausführungsform 70, wobei n₁ 1 bis 5 ist.
73. 73. Monomer gemäß Ausführungsform 70, wobei n₁ 1 bis 3 ist.
74. 74. Monomer gemäß Ausführungsform 70, wobei n₁ 3 ist.
75. 75. Monomer gemäß einer der Ausführungsformen 70 bis 74, wobei n₂ 1 bis 10 ist.
76. 76. Monomer gemäß einer der Ausführungsformen 70 bis 74, wobei n₂ 1 bis 5 ist.
77. 77. Monomer gemäß einer der Ausführungsformen 70 bis 74, wobei n₂ 1 bis 3 ist.
78. 78. Monomer gemäß einer der Ausführungsformen 70 bis 74, wobei n₂ 1 ist.
79. 79. Monomer gemäß einer der Ausführungsformen 69 bis 78, wobei (R_x)_0-4 (R_x)₀ ist.
80. 80. Monomer gemäß einer der Ausführungsformen 69 bis 79, wobei (R_y)_0-4 (R_y)₀ ist.
81. 81. Monomer gemäß Ausführungsform 70, welches folgende Struktur aufweist.
    
82. 82. Verwendung eines Monomers gemäß einer der Ausführungsformen 69 bis 81 als Photovernetzer.

Based on the above-mentioned surprising findings, the present invention was realized, which can be summarized as follows:

1. 1. Polymer having a structure of the general formula (I)
   
   wherein A ₁ is -H or -CH ₃ ; A ₂ is -H or -CH ₃ ; A ₃ is -H or -CH ₃ ; A ₄ is -H or -CH ₃ ; R ₁ , for each repeating unit, is independently selected from the group consisting of
   
   
   
   R ₂ , for each repeating unit, is independently selected from the group consisting of
   
   wherein each "spacer" is independently selected from the group consisting of linear or branched alkyl chains and linear or branched ethylene or propylene oxide chains, preferably independently selected from linear or branched C _1-20 alkyl chains; Rx, each independently, is -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and Ry, each independently, is -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; R ₃ , for each repeating unit, is independently selected from the group consisting of
   
   
   wherein n ₃ , n ₄ , n ₅ , n ₆ and n ₇ are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18; R ₄ , for each repeating unit, is independently selected from the group consisting of
   
   Y is a fragment A of a chain transfer reagent or an end group; and Z is a fragment B of the chain transfer reagent or an end group.
2. 2. Polymer according to embodiment 1, wherein R ₁ , for each repeating unit, is independently selected from the group consisting of
   
3. 3. Polymer according to embodiment 1, wherein R ₁ , for each repeating unit,
   
   is.
4. 4. Polymer according to embodiment 1, wherein R ₁ , for each repeating unit,
   
   is.
5. 5. Polymer according to any one of embodiments 1 to 4, wherein A ₁ is -H.
6. 6. Polymer according to any one of embodiments 1 to 4, wherein A ₁ is -CH ₃ .
7. 7. Polymer according to any one of embodiments 1 to 6, wherein R ₂ , for each repeating unit, is independently selected from the group consisting of
   
   wherein n ₁ and n ₂ are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; R _x are each independently -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and R _y , each independently, are -OH, halogen (Br, CI, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano.
8. 8. Polymer according to any one of embodiments 1 to 6, wherein R ₂ , for each repeating unit, is independently selected from the group consisting of
   
9. 9. Polymer according to any one of embodiments 1 to 6, wherein R ₂ , for each repeating unit,
   
   is.
10. 10. Polymer according to any one of embodiments 1 to 6, wherein R ₂ , for each repeating unit,
    
    wherein each "spacer" is independently selected from the group consisting of linear or branched alkyl chains and linear or branched ethylene or propylene oxide chains, preferably independently selected from linear or branched C _1-20 alkyl chains; R _x , each independently, is -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and R _y , each independently, is -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano.
11. 11. Polymer according to any one of embodiments 1 to 6, wherein R ₂ , for each repeating unit,
    
    wherein n ₁ and n ₂ are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; R _x , each independently, is -OH, halogen (Br, CI, I, or F), halogen-C _1-4 alkyl (eg -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 Alkynyl is -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and R _{y is} , each independently, -OH, halogen (Br, CI, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano.
12. 12. Polymer according to any one of embodiments 1 to 6, wherein R ₂ , for each repeating unit,
    
    is.
13. 13. Polymer according to any one of embodiments 1 to 12, wherein A ₂ is -H.
14. 14. Polymer according to any one of embodiments 1 to 12, wherein A ₂ is -CH ₃ .
15. 15. Polymer according to any one of embodiments 1 to 14, wherein R ₃ , for each repeating unit, is independently selected from the group consisting of
    
    where n ₃ , n ₄ , n ₅ , n ₆ and n ₇ are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18.
16. 16. Polymer according to any one of embodiments 1 to 14, wherein R ₃ , for each repeating unit,
    
    where n ₃ is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18.
17. 17. Polymer according to any one of embodiments 1 to 14, wherein R ₃ , for each repeating unit,
    
    is.
18. 18. Polymer according to any one of embodiments 1 to 14, wherein R ₃ , for each repeating unit, is independently selected from the group consisting of
    
19. 19. Polymer according to any one of embodiments 1 to 18, wherein A ₃ is -H.
20. 20. Polymer according to any one of embodiments 1 to 18, wherein A ₃ is -CH ₃ .
21. 21. Polymer according to any one of embodiments 1 to 20, wherein R ₄ , for each repeating unit,
    
    is.
22. 22. Polymer according to any one of embodiments 1 to 20, wherein R ₄ , for each repeating unit,
    
    is.
23. 23. Polymer according to any one of embodiments 1 to 20, wherein R ₄ , for each repeating unit,
    
    is.
24. 24. Polymer according to any one of embodiments 1 to 23, wherein A ₄ is -H.
25. 25. Polymer according to any one of embodiments 1 to 23, wherein A ₄ is -CH ₃ .
26. 26. Polymer according to embodiment 1, wherein R ₁ , for each repeating unit, is independently selected from the group consisting of
    
    R ₂ , for each repeating unit, is independently selected from the group consisting of
    
    R ₃ , for each repeat unit,
    
    and R ₄ , for each repeating unit, is independently selected from the group consisting of
    
27. 27. The polymer of embodiment 26, wherein A ₁ is -H, A ₂ is -H, A ₃ is -H, and A ₄ is -H.
28. 28. Polymer according to any one of embodiments 1 to 27, wherein Z is a fragment A of a chain transfer reagent and Y is a fragment B of the chain transfer reagent.
29. 29. Polymer according to any one of embodiments 1 to 28, wherein the chain transfer agent is selected from the group consisting of dithioesters, trithiocarbonates, xanthates and carbamates.
30. 30. Polymer according to any one of embodiments 1 to 27, wherein Y
    
    is, and Z
    
    wherein n ₈ is an integer from 1 to 24, preferably an integer from 1 to 14, more preferably an integer from 1 to 11; most preferably 1 or 11.
31. 31. Polymer according to any one of embodiments 1 to 27, wherein Y and Z are each an end group.
32. 32. Polymer according to any one of embodiments 1 to 31, wherein x _[2] is >0 to <1.
33. 33. Polymer according to any one of embodiments 1 to 32, wherein x _[3] is >0 to <1.
34. 34. Polymer according to any one of embodiments 1 to 33, wherein x _[4] is >0 to <1.
35. 35. Polymer according to any one of embodiments 1 to 31, wherein x _[2] is 0 and x _[3] is >0 to <1; and optionally x _[4] is >0 to <1.
36. 36. Polymer according to any one of embodiments 1 to 31, wherein x _[2] is >0 to <1 and x _[3] is 0; and optionally x _[4] is >0 to <1.
37. 37. Polymer according to any one of embodiments 1 to 31, wherein x _[2] is >0 to <1 and x _[3] is >0 to <1; and optionally x _[4] is >0 to <1.
38. 38. Polymer according to embodiment 1, selected from the group consisting of
    
    
    
    
    
    
    
    
    where n is an integer from 2 to 100,000, such as an integer from 50 to 10,000, e.g. an integer from 100 to 2,000.
39. 39. Polymer according to embodiment 1, selected from the group consisting of
    
    
    where n is an integer from 2 to 100,000, such as an integer from 50 to 10,000, e.g. an integer from 100 to 2,000.
40. 40. Polymer according to embodiment 1, selected from the group consisting of
    
    
    where n is an integer from 2 to 100,000, such as an integer from 50 to 10,000, e.g. an integer from 100 to 2,000.
41. 41. Polymer according to embodiment 1, selected from the group consisting of
    
    where n is an integer from 2 to 100,000, such as an integer from 50 to 10,000, e.g. an integer from 100 to 2,000.
42. 42. A hydrogel comprising a cross-linked polymer according to any one of embodiments 1 to 41.
43. 43. Coating comprising at least one layer comprising a polymer according to any one of embodiments 1 to 41.
44. 44. Coating according to embodiment 43, comprising a first layer comprising a polymer according to embodiment 35 and a second layer comprising a polymer according to embodiment 36.
45. 45. Coating according to embodiment 44, wherein the first and second layers are cross-linked to each other.
46. 46. A coating according to embodiment 43, comprising a layer comprising a polymer according to embodiment 37.
47. 47. A metal-containing substrate, characterized in that at least part of its surface is covered with a coating comprising at least one layer comprising a polymer according to any one of embodiments 1 to 41.
48. 48. Substrate according to embodiment 47, wherein the coating is a coating according to any one of embodiments 43 to 46.
49. 49. The substrate of embodiment 47 or 48, wherein the substrate is made of a metal.
50. 50. Substrate according to any one of embodiments 47 to 49, wherein the metal is selected from the group consisting of titanium, titanium alloys, aluminum, aluminum alloys, zinc, zinc alloys, tin, tin alloys, zirconium, zirconium alloys, tantalum, tantalum alloys, cobalt, cobalt alloys, nickel, nickel alloys, copper, copper alloys, magnesium, magnesium alloys, Molybdenum, molybdenum alloys, niobium, niobium alloys, chromium, chromium alloys, iron, iron alloys, stainless steel, and metal oxides thereof.
51. 51. The substrate of any of embodiments 47 to 51, wherein the metal comprises a metal oxide.
52. 52. The substrate of embodiment 51, wherein the metal oxide is selected from the group consisting of TiO ₂ , AlO ₂ , ZnO, ZrO ₂ , ITO, IZO, NiO _x , NiCoO _x , MoO _x Fe ₂ O ₃ , and Nb ₂ O ₅ .
53. 53. Substrate according to any one of embodiments 51 to 54, wherein the substrate comprises or consists of titanium, titanium oxide, or a titanium alloy.
54. 54. The substrate of embodiment 53, wherein the titanium alloy is Ti6Al4V or Ti6AL4V ELI.
55. 55. The substrate of embodiment 53, wherein the titanium oxide is TiO ₂ .
56. 56. A device comprising a substrate according to any one of embodiments 47 to 55.
57. 57. The device of embodiment 56, wherein the substrate forms at least a portion of the surface of the device.
58. 58. The device of embodiment 56 or 57, wherein the device is a medical device.
59. 59. Device according to any one of embodiments 56 to 58, wherein the device is an implant.
60. 60. Use of a device according to embodiment 59 as a short-term implant.
61. 61. A method for coating a substrate, comprising the steps
    1. (a) providing a metal-containing substrate, and
    2. (b) contacting the substrate with a solution of the polymer according to any one of embodiments 1 to 41;
    3. (c) optionally drying the substrate; and
    4. (d) where appropriate, UV irradiation.
62. 62. A method for coating a device, comprising the steps
    1. (a) providing a device comprising a metal-containing substrate, and
    2. (b) contacting the device or substrate with a solution of the polymer according to any one of embodiments 1 to 41;
    3. (c) optionally drying the substrate; and
    4. (d) where appropriate, UV irradiation.
63. 63. The method according to embodiment 61 or 62, wherein step (b) comprises a first contacting of the device or the substrate with a solution of the polymer according to embodiment 39, followed by a second contacting of the device or the substrate with a solution of the polymer according to embodiment 40 (two-layer system).
64. 64. The method according to embodiment 61 or 62, wherein step (b) comprises contacting the device or the substrate with a solution of the polymer according to embodiment 41 (single layer system).
65. 65. The method of any of embodiments 61 to 64, wherein contacting comprises spraying or pouring with or immersing in the solution.
66. 66. Use of the polymer according to any one of embodiments 1 to 41 as an anti-adhesive coating, preferably as an anti-adhesive coating on a medical device, further preferably as an anti-adhesive coating on an implant.
67. 67. Polymer according to any one of embodiments 1 to 41 for use in a method for treating a bone fracture in a patient, the method comprising
    1. a) providing an implant comprising a substrate characterized in that at least part of its surface is covered with a coating comprising at least one layer comprising a polymer according to any of embodiments 1 to 45; and
    2. b) Inserting the implant at a bone repair site or in the area of the bone fracture in the patient.
68. 68. A polymer for use according to embodiment 67, wherein the implant is the implant of embodiment 59.
69. 69. Monomer having a structure of the general formula (II)
    
    wherein each "spacer" is independently selected from the group consisting of linear or branched alkyl chains and linear or branched ethylene or propylene oxide chains, preferably independently selected from linear or branched C _1-20 alkyl chains; R _x , each independently, is -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and R _y , each independently, is -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano.
70. 70. Monomer having a structure of the general formula (IIa)
    
    wherein n ₄ and n ₂ are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; R _{x is} , each independently, -H, -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. - CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and R _y , each independently, is -H, -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano.
71. 71. The monomer of embodiment 70, wherein n ₁ is 1 to 10.
72. 72. The monomer of embodiment 70, wherein n ₁ is 1 to 5.
73. 73. The monomer of embodiment 70, wherein n ₁ is 1 to 3.
74. 74. The monomer of embodiment 70, wherein n ₁ is 3.
75. 75. A monomer according to any one of embodiments 70 to 74, wherein n ₂ is 1 to 10.
76. 76. A monomer according to any one of embodiments 70 to 74, wherein n ₂ is 1 to 5.
77. 77. A monomer according to any one of embodiments 70 to 74, wherein n ₂ is 1 to 3.
78. 78. The monomer of any of embodiments 70 to 74, wherein n ₂ is 1.
79. 79. The monomer of any one of embodiments 69 to 78, wherein (R _x ) _0-4 (R _x ) ₀ .
80. 80. The monomer of any of embodiments 69 to 79, wherein (R _y ) _0-4 (R _y ) ₀ .
81. 81. A monomer according to embodiment 70, which has the following structure.
    
82. 82. Use of a monomer according to any one of embodiments 69 to 81 as a photocrosslinker.

Description of the images

• : Tenocyte adhesion on cell culture plate, coated versus uncoated.
• : Tenocyte adhesion on titanium discs. coated (A) versus uncoated (B)
• : Staph. aureus CFUs after incubation on a plate coated with non-antibacterial polymer (A) versus a plate coated with antibacterial polymer (B).

Detailed description of the invention

As already mentioned above, the present invention provides hydrophilic (co)polymers with chemically reactive (covalent) bound anchor groups and/or crosslinking molecules, which allow attachment to the underlying substrate or linking of these polymers to form networks. Coating short-term implants with such water-swellable polymer networks (hydrogels) prevents adhesion of cells and tissue to the surface (antifouling) without causing cytotoxicity and at the same time achieves an intrinsic antibacterial effect without the need to add additional antibiotics or bactericides. Since the surrounding tissue cannot adhere to an anti-adhesive coated implant, it is not damaged when the implant is removed. In addition, the intrinsic antibacterial effect of the coating prevents any infection that may occur during implantation.

The polymer chains described here and on which the hydrogel is based consist of hydrophilic main monomers and crosslinking monomers, some with antibacterial structural motifs, and/or dedicated anchor groups for the corresponding implant substrate. By carefully selecting these modularly combinable monomers, it is possible to produce biocompatible, antiadhesive and antibacterial polymer networks at the same time.

When presenting the (co)polymers according to the invention, a random distribution of the repeat units from the monomers used is to be assumed. The number of repeat units "n" specified for a normal polymer chain is only partially applicable in this case, since the repeat units within the polymer chain do not repeat in a regular sequence. For this reason, the specification of a repeat unit "n" in the following formulas, in particular the general formula (I), has been omitted. In the present case, it would therefore also be possible to define repeat units in the following formulas that can be in the range of n = 2 - 100,000, such as 50-10,000. The square brackets nevertheless indicate a repeating sequence of the repeat units in question in accordance with the usual polymer chain representation according to the state of the art. The specification "n" could therefore be specified in the square brackets in the following formulas, but this was omitted for the reasons mentioned above. The representation of the copolymer composition of different monomers with " / " is chosen according to the IUPAC recommendation.

wobei A₁, A₂, A₃, A₄, R₁, R₂, R₃, R₄, Y und Z wie hierin beschrieben sind.According to the invention, in a first aspect, a (co)polymer of the general structural formula (I) with a random distribution of the repeating units is provided:

where A ₁ , A ₂ , A ₃ , A ₄ , R ₁ , R ₂ , R ₃ , R ₄ , Y and Z are as described herein.

The random distribution of the repeating units is given by the compositions (molar fractions) x, where x with x _[1] , x _[2] , x _[3] and x _[4] represents a molecular structure of a number of repeating units and the sum of the mole fractions x of the repeating units with x _[1] , x _[2] , x _[3] and x _[4] = 1.

A ₁ /R ₁ , A ₂ /R ₂ , A ₃ /R ₃ and A ₄ /R ₄ correspond to the repeat units of main monomer, anchor monomer, crosslinker monomer and comonomer respectively. The respective monomer types defined by A ₁ /R ₁ , A ₂ /R ₂ , A ₃ /R ₃ and A ₄ /R ₄ can be identical in the polymer according to the invention. However, a polymer according to the invention can also comprise combinations of different repeat units of the same monomer type. Accordingly, the respective repeat units of the same monomer type can differ in the radical R. For example, a polymer according to the invention can comprise different repeat units of the main monomer defined by A ₁ /R ₁ , which differ, for example, in the radical R ₁ .

wobei
A₁ -H oder -CH₃ ist;
A₂ -H oder -CH₃ ist;
A₃ -H oder -CH₃ ist;
A₄ -H oder -CH₃ ist;
R₁, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus

R₂, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus

wobei jeder „Spacer"jeweils unabhängig voneinander ausgewählt ist aus der Gruppe bestehend aus linearen oder verzweigten Alkylketten und linearen oder verzweigten Ethylen- oder Propylenoxidketten, vorzugweise unabhängig voneinander ausgewählt aus linearen oder verzweigen C_1-20-Alkylketten;
R_x, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; und
R_y, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist;
R₃, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus

wobei n₃, n₄, n₅, n₆ und n₇ jeweils unabhängig voneinander 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 oder 18 ist;
R₄, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus

Y ein Fragment A eines Kettenübertragungsreagenzes oder eine Endgruppe ist; und
Z ein Fragment B des Kettenübertragungsreagenzes oder eine Endgruppe ist.In particular, a polymer is provided which has a structure of the general formula (I)

where
A ₁ is -H or -CH ₃ ;
A ₂ is -H or -CH ₃ ;
A ₃ is -H or -CH ₃ ;
A ₄ is -H or -CH ₃ ;
R ₁ , for each repeating unit, is independently selected from the group consisting of

R ₂ , for each repeating unit, is independently selected from the group consisting of

wherein each "spacer" is independently selected from the group consisting of linear or branched alkyl chains and linear or branched ethylene or propylene oxide chains, preferably independently selected from linear or branched C _1-20 alkyl chains;
R _x , each independently, is -OH, halogen (Br, CI, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and
R _{y is} , each independently, -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano;
R ₃ , for each repeating unit, is independently selected from the group consisting of

wherein n ₃ , n ₄ , n ₅ , n ₆ and n ₇ are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18;
R ₄ , for each repeating unit, is independently selected from the group consisting of

Y is a fragment A of a chain transfer reagent or an end group; and
Z is a fragment B of the chain transfer reagent or an end group.

According to some preferred embodiments, R ₁ , for each repeating unit, is independently selected from the group consisting of

According to some particularly preferred embodiments, R ₁ , for each repeating unit,

According to some particularly preferred embodiments, R ₁ , for each repeating unit,

In some embodiments, A ₁ is -H.

In some embodiments, A ₁ is -CH ₃ .

und A₁ -H.According to some particularly preferred embodiments, R ₁ , for each repeating unit,

and A ₁ -H.

und A₁ -H.According to some particularly preferred embodiments, R ₁ , for each repeating unit,

and A ₁ -H.

wobei n₁ und n₂ jeweils unabhängig voneinander 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 oder 20 ist;
R_x, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; und
R_y, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. - CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, - OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist.According to some embodiments, R ₂ , for each repeating unit, is independently selected from the group consisting of

wherein n ₁ and n ₂ are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;
R _x , each independently, is -OH, halogen (Br, CI, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and
R _{y is} , each independently, -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano.

According to some embodiments, R ₂ , for each repeating unit, is independently selected from the group consisting of

wobei jeder „Spacer" jeweils unabhängig voneinander ausgewählt ist aus der Gruppe bestehend aus linearen oder verzweigten Alkylketten und linearen oder verzweigten Ethylen- oder Propylenoxidketten, vorzugweise unabhängig voneinander ausgewählt aus linearen oder verzweigen C_1-20-Alkylketten;
R_x, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; und
R_y, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist.According to some embodiments, R ₂ , for each repeating unit,

wherein each "spacer" is independently selected from the group consisting of linear or branched alkyl chains and linear or branched ethylene or propylene oxide chains, preferably independently selected from linear or branched C _1-20 alkyl chains;
R _x , each independently, is -OH, halogen (Br, CI, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and
R _{y is} , each independently, -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano.

ist,
wobei n₁ und n₂ jeweils unabhängig voneinander 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 oder 20 ist;
R_x, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; und
R_y, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. - CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, - OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist.According to some embodiments, R ₂ , for each repeating unit,

is,
wherein n ₁ and n ₂ are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;
R _x , each independently, is -OH, halogen (Br, CI, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and
R _{y is} , each independently, -OH, halogen (Br, CI, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, - OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano.

According to some embodiments, R ₂ , for each repeating unit,

In some embodiments, A ₂ is -H.

In some embodiments, A ₂ is -CH ₃ .

wobei n₁ und n₂ jeweils unabhängig voneinander 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 oder 20 ist;
R_x, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; und
R_y, jeweils unabhängig voneinander, -OH, Halogen (Br, CI, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; und
A₂ ist -H.According to some embodiments, R ₂ , for each repeating unit, is independently selected from the group consisting of

wherein n ₁ and n ₂ are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;
R _x , each independently, is -OH, halogen (Br, CI, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and
R _y , each independently, is -OH, halogen (Br, CI, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and
A ₂ is -H.

In some embodiments, (R _x ) _0-4 (R _x ) ₀ .

According to some embodiments, (R _y ) _0-4 (R _y ) ₀ .

und A₂ ist -H.According to some preferred embodiments, R ₂ , for each repeating unit, is independently selected from the group consisting of

and A ₂ is -H.

wobei n₃, n₄, n₅, n₆ und n₇ jeweils unabhängig voneinander 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 oder 18 ist.According to some embodiments, R ₃ , for each repeating unit, is independently selected from the group consisting of

where n ₃ , n ₄ , n ₅ , n ₆ and n ₇ are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18.

wobei n₃ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 oder 18 ist.According to some embodiments, R ₃ , for each repeating unit,

where n ₃ is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18.

wobei n₄ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 oder 18 ist.According to some embodiments, R ₃ , for each repeating unit,

where n ₄ is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18.

wobei n₅ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 oder 18 ist.According to some embodiments, R ₃ , for each repeating unit,

where n ₅ is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18.

wobei n₆ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 oder 18 ist.According to some embodiments, R ₃ , for each repeating unit,

where n ₆ is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18.

wobei n₇ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 oder 18 ist.According to some embodiments, R ₃ , for each repeating unit,

where n ₇ is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18.

According to some preferred embodiments, R ₃ , for each repeating unit,

According to some embodiments, R ₃ , for each repeating unit, is independently selected from the group consisting of

In some embodiments, A ₃ is -H.

In some embodiments, A ₃ is -CH ₃ .

wobei n₃ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 oder 18 ist; und A₃ ist -H.According to some preferred embodiments, R ₃ , for each repeating unit, is ,

where n ₃ is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18; and A ₃ is -H.

und A₃ ist -H.According to some preferred embodiments, R ₃ , for each repeating unit,

and A ₃ is -H.

und A₃ ist -H.According to some embodiments, R ₃ , for each repeating unit, is independently selected from the group consisting of

and A ₃ is -H.

According to some embodiments, R ₄ , for each repeating unit,

According to some embodiments, R ₄ , for each repeating unit,

According to some embodiments, R ₄ , for each repeating unit,

In some embodiments, A is ₄ -H.

In some embodiments, A ₄ is -CH ₃ .

und A₄ ist -H.According to some preferred embodiments, R ₄ , for each repeating unit,

and A ₄ is -H.

und A₄ ist -H.According to some preferred embodiments, R ₄ , for each repeating unit,

and A ₄ is -H.

und A₄ ist -H.According to some preferred embodiments, R ₄ , for each repeating unit,

and A ₄ is -H.

ist R₂, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus

ist R₃, für jede Wiederholungseinheit,

und ist R₄, für jede Wiederholungseinheit, unabhängig ausgewählt aus der Gruppe bestehend aus

According to some preferred embodiments, R ₁ , for each repeating unit, is independently selected from the group consisting of

R ₂ , for each repeating unit, is independently selected from the group consisting of

is R ₃ , for each repeating unit,

and R ₄ , for each repeating unit, is independently selected from the group consisting of

ist R₂, für jede Wiederholungseinheit, unabhängig ausgewählt ist aus der Gruppe bestehend aus

ist R₃, für jede Wiederholungseinheit,

ist R₄, für jede Wiederholungseinheit, unabhängig ausgewählt aus der Gruppe bestehend aus

According to some preferred embodiments, R ₁ , for each repeating unit, is independently selected from the group consisting of

R ₂ , for each repeating unit, is independently selected from the group consisting of

is R ₃ , for each repeating unit,

R ₄ , for each repeating unit, is independently selected from the group consisting of

In some embodiments, A ₁ is -H, A ₂ is -H, A ₃ is -H, and A ₄ is -H.

Z is a fragment A of a chain transfer reagent and Y is a fragment B of the chain transfer reagent.

Suitable chain transfer reagents for reversible addition-fragmentation chain transfer (RAFT) polymerization are well known to those skilled in the art and are generally from the classes of dithioesters, trithiocarbonates, xanthates and carbamates.

In the case of an atom transfer radical polymerization (ATRP) reaction, the terminal variables Y and Z of the polymer correspond to the commonly occurring end groups, preferably -Cl and -Br, or organic fragments from the ATRP initiator component, which usually consist of organohalides such as carbon tetrachloride, halogenated esters, halogenated alkylbenzenes and sulfonyl halides.

In the case of free radical (FR) polymerization, the terminal variables Y and Z of the polymer correspond to the commonly occurring saturated or unsaturated organic end groups or abstracted hydrogen atoms formed by transfer, disproportionation or combination reactions, as well as initiator fragments, such as the isobutyronitrile residue of azobis(isobutyronitrile) (AIBN).

2-{[(Dodecylthio)carbothioyl]-thio}-2-methylpropansäure (DMP), und

2-{[(Ethylthio)carbothioyl]-thio}-2-methylpropansäure (EMP).Non-limiting examples of chain transfer reagents which were also used in the embodiments are

2-{[(Dodecylthio)carbothioyl]-thio}-2-methylpropanoic acid (DMP), and

2-{[(Ethylthio)carbothioyl]-thio}-2-methylpropanoic acid (EMP).

und Z ist

wobei n₈ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 oder 24 ist.According to some preferred embodiments, Y

and Z is

where n ₈ is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24.

According to some preferred embodiments, n ₈ is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 18 19 or 20.

According to some preferred embodiments, n ₈ is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15.

According to some preferred embodiments, n ₈ is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11.

According to some particularly preferred embodiments, n ₈ is 1.

According to some particularly preferred embodiments, n is ₈ 11.

According to some embodiments, Y and Z are each an end group.

According to some preferred embodiments, x _[2] is >0 to <1.

According to some preferred embodiments, x _[3] is >0 to <1.

According to some preferred embodiments, x _[4] is >0 to <1.

According to some particularly preferred embodiments, x _[2] is 0 and x _[3] >0 to <1; and optionally x _[4] is >0 to <1. In these embodiments, the polymer can advantageously be used as an anchor polymer in a two-layer system.

According to some particularly preferred embodiments, x _[2] is >0 to <1 and x _[3] is 0; and optionally x _[4] is >0 to <1. In these embodiments, the polymer can advantageously be used as an anti-adhesive polymer in a two-layer system.

According to some particularly preferred embodiments, x _[2] is >0 to <1 and x _[3] is >0 to <1; and optionally x _[4] is >0 to <1. In these embodiments, the polymer can advantageously be used both as an anchor polymer and as an anti-adhesive polymer in a single-layer system.

RAFT-Poly(HEAm₉₃-ran-APAm₅-ran-BPAm₂)-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymersiation P2

RAFT-Poly(HEAm₉₃-ran-AEAm₅-ran-BPAm₂)-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymersiation P3

RAFT-Poly(HEAm₇₄-ran-HPAm₂₄-ran-BPAm₂)-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymersiation P4

RAFT-Poly(HEAm₄₉-ron-HPAm₄₉-ran-BPAm₂)-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymersiation P5

RAFT-Poly(HPAm₉₃-ran-APAm₅-ran-BPAm₂)-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymersiation P6

RAFT-Poly(HPAm₉₃-ran-AEAm₅-ran-BPAm₂)-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymersiation P7

RAFT-Poly(HEAm₂₄-ran-HPAm₇₄-ran-BPAm₂)-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymersiation P8

RAFT-Poly(HEAm₉₃-ran-AaAm₅-ran-BPAm₂)-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymersiation P9

RAFT-Poly(HPAm₉₃-ran-AaAm₅-ran-BPAm₂)-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymersiation P10

Poly(HEAm₉₈-ran-BPQAAm₂) Freie Radikalische (FR) Polymerisation P11

Poly(HEAm₇₄-ran-HPAm₂₄-ran-BPAm₂) Freie Radikalische (FR) Polymerisation P12

Poly(HEAm₄₉-ron-HPArr)₄₉-ran-BPQAAm₂) Freie Radikalische (FR) Polymerisation P13

Poly(HPAm₉₈-ran-BPQAAm₂) Freie Radikalische (FR) Polymerisation P14

Poly(HEAm₇₄-ran-HPAm₂₄-ran-BPQAAm₂) Freie Radikalische (FR) Polymerisation P15

Poly(HEAm₉₈-ran-BPAm₂) Freie Radikalische (FR) Polymerisation P16

Poly(HPAm₉₈-ran-BPAm₂) Freie Radikalische (FR) Polymerisation P17

Poly(HEAm₄₉-ran-HPAm)₄₉-ran-BPAm₂) Freie Radikalische (FR) Polymerisation P18

RAFT-Poly(HEAm₇₅-ran-VPA₂₀-ran-BPAm₅)-EMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymersiation P19

Poly(HEAm₇₅-ran-VPA₂₀-ran-BPAm₅) Freie Radikalische (FR) Polymerisation AP1

Poly(HEAm₈₀-ran-VPA₂₀) Freie Radikalische (FR) Polymerisation AP2

Poly(HEAm₉₀-ran-VPA₁₀) Freie Radikalische (FR) Polymerisation AP3

Poly(HEAm₉₅-ran-VPA₅) Freie Radikalische (FR) Polymerisation AP4

Poly(HEAm₉₈-ran-VPA₂) Freie Radikalische (FR) Polymerisation AP5

RAFT-Poly(HEAm₈₀-ran-VPA₂₀)-EMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymersiation Exemplary polymers according to the invention are listed in Table 1 below. Table 1 abbreviation structure Surname Polymerization type P1

RAFT-Poly(HEAm ₉₃ -ran-APAm ₅ -ran-BPAm ₂ )-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization P2

RAFT-Poly(HEAm ₉₃ -ran-AEAm ₅ -ran-BPAm ₂ )-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization P3

RAFT-Poly(HEAm ₇₄ -ran-HPAm ₂₄ -ran-BPAm ₂ )-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization P4

RAFT-Poly(HEAm ₄₉ -ron-HPAm ₄₉ -ran-BPAm ₂ )-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization P5

RAFT-Poly(HPAm ₉₃ -ran-APAm ₅ -ran-BPAm ₂ )-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization P6

RAFT-Poly(HPAm ₉₃ -ran-AEAm ₅ -ran-BPAm ₂ )-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization P7

RAFT-Poly(HEAm ₂₄ -ran-HPAm ₇₄ -ran-BPAm ₂ )-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization P8

RAFT-Poly(HEAm ₉₃ -ran-AaAm ₅ -ran-BPAm ₂ )-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization P9

RAFT-Poly(HPAm ₉₃ -ran-AaAm ₅ -ran-BPAm ₂ )-DMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization P10

Poly(HEAm ₉₈ -ran-BPQAAm ₂ ) Free Radical (FR) Polymerization P11

Poly(HEAm ₇₄ -ran-HPAm ₂₄ -ran-BPAm ₂ ) Free Radical (FR) Polymerization P12

Poly(HEAm ₄₉ -ron-HPArr) ₄₉ -ran-BPQAAm ₂ ) Free Radical (FR) Polymerization P13

Poly(HPAm ₉₈ -ran-BPQAAm ₂ ) Free Radical (FR) Polymerization P14

Poly(HEAm ₇₄ -ran-HPAm ₂₄ -ran-BPQAAm ₂ ) Free Radical (FR) Polymerization P15

Poly(HEAm ₉₈ -ran-BPAm ₂ ) Free Radical (FR) Polymerization P16

Poly(HPAm ₉₈ -ran-BPAm ₂ ) Free Radical (FR) Polymerization P17

Poly(HEAm ₄₉ -ran-HPAm) ₄₉ -ran-BPAm ₂ ) Free Radical (FR) Polymerization P18

RAFT-Poly(HEAm ₇₅ -ran-VPA ₂₀ -ran-BPAm ₅ )-EMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization P19

Poly(HEAm ₇₅ -ran-VPA ₂₀ -ran-BPAm ₅ ) Free Radical (FR) Polymerization AP1

Poly(HEAm ₈₀ -ran-VPA ₂₀ ) Free Radical (FR) Polymerization WP2

Poly(HEAm ₉₀ -ran-VPA ₁₀ ) Free Radical (FR) Polymerization WP3

Poly(HEAm ₉₅ -ran-VPA ₅ ) Free Radical (FR) Polymerization AP4

Poly(HEAm ₉₈ -ran-VPA ₂ ) Free Radical (FR) Polymerization AP5

RAFT-Poly(HEAm ₈₀ -ran-VPA ₂₀ )-EMP Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization

n = 2 to 100,000. The abbreviation -ran- stands for the random sequence of repeat units in the copolymer. Molar masses (FR): 50 - 500 kg/mol. Molar masses (RAFT): 2 - 40 kg/mol. For all specific polymer structures, the number written in the index corresponds to the molar ratio of the feed-in. Example: Poly(HEAm ₉₈ -ran-BPAm ₂ ) means that 98 mol% HEAm and 2 mol% BPAm were used as the molar ratio at the beginning of the polymerization.

und

wobei n eine Ganzzahl von 2 bis 100.000 ist, wie beispielsweise eine Ganzzahl von 50 bis 10.000, z.B. eine Ganzzahl von 100 bis 2.000.Particularly preferred polymers according to the invention are:

and

where n is an integer from 2 to 100,000, such as an integer from 50 to 10,000, e.g. an integer from 100 to 2,000.

wobei n eine Ganzzahl von 2 bis 100.000 ist, wie beispielsweise eine Ganzzahl von 50 bis 10.000, z.B. eine Ganzzahl von 100 bis 2.000.A particularly preferred anchor polymer according to the invention is:

where n is an integer from 2 to 100,000, such as an integer from 50 to 10,000, e.g. an integer from 100 to 2,000.

Based on the previously described polymers of the invention, the present invention provides in a further aspect a hydrogel comprising a cross-linked polymer according to the invention.

In a further aspect, the present invention provides a coating comprising at least one layer comprising a polymer according to the invention.

A coating according to the invention can take various forms depending on the method of manufacture and the polymer composition. Exemplary forms of application include single-layer and two-layer (sandwich) systems.

According to some embodiments, the coating comprises a layer comprising a polymer of the general formula (I) with x _[2] >0 to <1, x _[3] >0 to <1; and optionally x _[4] >0 to <1.

According to some further embodiments, the coating comprises a first layer comprising a polymer of the general formula (I) with X _[2] 0, x _[3] >0 to <1; and optionally x [4] >0 to <1, and a second layer comprising a polymer of the general formula (I) with X _[2] >0 to <1, x _[3] = 0; and optionally x [4] >0 to <1. In these embodiments, the first and second layers can advantageously be cross-linked with one another.

In a further aspect, the present invention provides a metal-containing substrate characterized in that at least a part of its surface is coated with a coating comprising at least one layer comprising a polymer according to the invention.

According to some embodiments, at least a portion of the surface of the metal-containing substrate is coated with a coating according to the invention.

According to some embodiments, the entire surface of the metal-containing substrate is coated with a coating according to the invention.

According to some embodiments, the substrate is made of a metal.

According to some embodiments, the substrate is made of a metal that is used in implants.

Exemplary metals that can serve as a substrate according to the invention include titanium, titanium alloys, aluminum, aluminum alloys, zinc, zinc alloys, tin, tin alloys, zirconium, zirconium alloys, tantalum, tantalum alloys, cobalt, cobalt alloys, nickel, nickel alloys, copper, copper alloys, magnesium, magnesium alloys, molybdenum, molybdenum alloys, niobium, niobium alloys, chromium, chromium alloys, iron, iron alloys, stainless steel, and metal oxides thereof.

Examples of metals that are commonly used in implants, but are not limiting, are cobalt-chromium-molybdenum alloys, e.g. implavit ^® CoCrMo, unalloyed titanium (pure titanium), titanium-aluminum-vanadium alloys such as TiAl6V4 or Ti6AL4V ELI, titanium-aluminum-niobium alloys such as TiAl6Nb7, and stainless steel.

According to some embodiments, the metal comprises a metal oxide, preferably on its surface.

Non-limiting examples of metal oxides include TiO ₂ , AlO ₂ , ZnO, ZrO ₂ , ITO, IZO, NiO _x , NiCoO _x , MoO _x Fe ₂ O ₃ , or Nb ₂ O ₅ .

According to some embodiments, the metal comprises titanium oxide, for example TiO ₂ .

According to some embodiments, the substrate comprises or consists of titanium, titanium oxide, or a titanium alloy. Exemplary titanium alloys are described above.

In a further aspect, the present invention provides a device comprising a substrate according to the invention.

According to some embodiments, the substrate forms at least a portion of the surface of the device.

According to some embodiments, the substrate forms the entire surface of the device.

According to some embodiments, the device is a medical device, such as an implant.

Accordingly, in a particular aspect, the present invention provides an implant which is characterized in that at least part of its metal-containing surface is coated with a coating according to the invention. Further embodiments emerge from those described above.

As already mentioned above, a coating of, for example, implants with the polymer networks according to the invention prevents, among other things, adhesion of cells and tissue to the surface of the implant. Implants which have a coating according to the invention are therefore particularly suitable as short-term implants. Accordingly, in a further aspect, the present invention provides the use of an implant according to the invention as a short-term implant.

In further aspects, the present invention provides methods for coating substrates and devices (such as medical devices such as an implant).

1. (a) Bereitstellen eines metallhaltigen Substrates, und
2. (b) In-Kontakt-Bringen des Substrates mit einer Lösung eines Polymers gemäß der Erfindung;
3. (c) gegebenenfalls Trocknen des Substrates; und
4. (d) gegebenenfalls UV-Bestrahlung.

In particular, the present invention provides a method for coating a substrate comprising the steps

1. (a) providing a metal-containing substrate, and
2. (b) contacting the substrate with a solution of a polymer according to the invention;
3. (c) optionally drying the substrate; and
4. (d) where appropriate, UV irradiation.

1. (a) Bereitstellen einer Vorrichtung, umfassend ein metallhaltiges Substrat, und
2. (b) In-Kontakt-Bringen der Vorrichtung bzw. des Substrates mit einer Lösung eines Polymers gemäß der Erfindung;
3. (c) gegebenenfalls Trocknen des Substrates; und
4. (d) gegebenenfalls UV-Bestrahlung.

Furthermore, the present invention provides a method for coating a device, such as a medical device, comprising the steps

1. (a) providing a device comprising a metal-containing substrate, and
2. (b) contacting the device or substrate with a solution of a polymer according to the invention;
3. (c) optionally drying the substrate; and
4. (d) where appropriate, UV irradiation.

According to some embodiments, step (b) comprises a first contacting of the device or the substrate with a solution of a polymer of the general formula (I) with X _[2] 0, x _[3] >0 to <1; and optionally x [4] >0 to <1, followed by a second contacting of the device or the substrate with a solution of a polymer of the general formula (I) with X _[2] >0 to <1, x _[3] = 0; and optionally x _[4] >0 to <1 (two-layer system). After the first contacting and the second contacting, a drying step can be carried out in each case.

According to some embodiments, step (b) comprises contacting the device or substrate with a solution of a polymer of the general formula (I) with X _[2] >0 to <1, x _[3] >0 to <1; and optionally x _[4] >0 to <1 (single layer system).

The contacting can be carried out by any method known to those skilled in the art for applying polymer solutions to surfaces, such as by spraying or pouring with or immersing in the solution(s).

At the end of the procedure, a “washing step” can be performed to remove non-adhering polymer residues and/or low molecular weight compounds.

In a further aspect, the present invention provides the use of a polymer according to the invention as an anti-adhesive coating, preferably as an anti-adhesive coating on a medical device, further preferably as an anti-adhesive coating on an implant.

1. a) Bereitstellen eines Implantats, umfassend ein Substrat, das dadurch gekennzeichnet ist, dass mindestens ein Teil seiner Oberfläche mit einerBeschichtung überzogen ist, welche mindestens eine Schicht umfasst, die ein erfindungsgemäßes Polymer umfasst; und
2. b) Einsetzen des Implantats an einer Knochenreparaturstelle oder im Bereich der Knochenfraktur im Patienten.

In a further aspect, the present invention provides a polymer according to the invention for use in a method of treating a bone fracture in a patient, the method comprising the following steps

1. a) providing an implant comprising a substrate characterized in that at least part of its surface is covered with a coating comprising at least one layer comprising a polymer according to the invention; and
2. b) Inserting the implant at a bone repair site or in the area of the bone fracture in the patient.

According to some embodiments, the coating is a coating according to the invention.

According to some embodiments, the implant is an implant according to the invention.

wobei jeder „Spacer" jeweils unabhängig voneinander ausgewählt ist aus der Gruppe bestehend aus linearen oder verzweigten Alkylketten und linearen oder verzweigten Ethylen- oder Propylenoxidketten, vorzugweise unabhängig voneinander ausgewählt aus linearen oder verzweigen C_1-20-Alkylketten;
R_x, jeweils unabhängig voneinander, -OH, Halogen (Br, Cl, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; und
R_y, jeweils unabhängig voneinander, -OH, Halogen (Br, Cl, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist.In a further aspect, the present invention provides a monomer having a structure of the general formula (II)

wherein each "spacer" is independently selected from the group consisting of linear or branched alkyl chains and linear or branched ethylene or propylene oxide chains, preferably independently selected from linear or branched C _1-20 alkyl chains;
R _x , each independently, is -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and
R _{y is} , each independently, -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano.

wobei n₁ und n₂ jeweils unabhängig voneinander 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 oder 20 ist;
R_x, jeweils unabhängig voneinander, -OH, Halogen (Br, Cl, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist; und
R_y, jeweils unabhängig voneinander, -OH, Halogen (Br, Cl, I, oder F), Halogen-C_1-4 Alkyl (z.B. -CF₃, -CCL₃, -CBr₃, -Cl₃), -NH₂, -C_1-4 Alkyl, -C_2-4 Alkenyl, -C_2-4 Alkinyl, -OC_1-4 Alkyl, -OC_2-4 Alkenyl, -OC_2-4 Alkinyl -NO₂, -SH, -SO₂H, -SO₃H, -NCS, -SCN, -COOH oder Cyano ist.According to some embodiments, the present invention provides a monomer having a structure of the general formula (Ila)

wherein n ₁ and n ₂ are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;
R _x , each independently, is -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and
R _{y is} , each independently, -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano.

According to some embodiments, n ₁ is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

According to some embodiments, n ₁ is 1, 2, 3, 4, or 5.

According to some embodiments, n ₁ is 1, 2, or 3.

According to some embodiments, n ₁ is 3.

According to some embodiments, n ₂ is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

According to some embodiments, n ₂ is 1, 2, 3, 4, or 5.

According to some embodiments, n ₂ is 1, 2, or 3.

According to some embodiments, n ₂ is 1.

According to some embodiments, the monomer of formula (Ila) has the following structure

Monomers of formula (II) or (IIa) are multifunctional, i.e. they function as monomers, photocrosslinkers and also have an antibacterial effect.

In a further aspect, the present invention provides the use of a monomer of formula (II) or (IIa) as a photocrosslinker.

Having generally described this invention, a further understanding can be obtained by reference to the following specific embodiments which are given by way of illustration only and are not to be taken as limiting unless otherwise specified.

Examples of implementation

1. Synthesis of polymers

mit A₁ = -H, A₂ = -H, A₃ = -H, und A₄₌-H.The polymer chains underlying the hydrogel are produced from combinations of two to four of the corresponding monomers via free radical polymerization or "reversible addition fragmentation chain transfer polymerization" (RAFT polymerization) with the addition of radical initiators and any chain transfer reagents (in the case of RAFT polymerization). The polymers synthesized in the present embodiments are listed in Table 1 above and have been abbreviated with the designations P1-P19 and AP1 to AP5.

with A ₁ = -H, A ₂ = -H, A ₃ = -H, and A _{4 =} -H.

Generic polymer structure: a) hydrophilic main monomer (R ₁ ), b) benzophenone derivative as crosslinking monomer (R ₂ ), c) anchor monomer for titanium surfaces (R ₃ ) and d) comonomer (R ₄ ), as well as e) chain transfer reagent (Z and Y) or end groups (Z and Y).

1.1 Repeating units and reagents

a) Main hydrophilic monomer:

The synthesized polymers consist of at least one of the above-mentioned main monomers or of their combinations in variable ratios with proportions of 20-99.5 mol%.

b) Benzophenone derivative as crosslinking monomer:

The synthesized polymers contain one of the above-mentioned benzophenone-based crosslinking monomers in a proportion of 0.5-10 mol%. The crosslinking monomer with quaternary ammonium group can induce an intrinsic antibacterial effect of the coating.

c) Anchor monomer for titanium surfaces:

The polymer coating contains the anchor monomer vinylphosphonic acid (VPA) with a proportion of 1-50 mol% in the anchor polymer layer (sandwich structure) or in the coating polymer (single-layer system).

d) Comonomer:

The synthesized polymers contain one of the above-mentioned comonomers in a proportion of 0.5-10 mol%.

e) Chain transfer reagent (Z and Y)

The polymers synthesized in the embodiments described here contain the chain transfer reagent 2-{[(dodecylthio)carbothioyl]-thio}-2-methylpropanoic acid (DMP) or 2{[(ethylthio)carbothioyl]-thio}-2-methylpropanoic acid (EMP) in a proportion of 0-2 mol% (0 mol% = free radical polymerization, >0 mol% = RAFT polymerization).

f) Radical initiator:

The proportion of the initiator azobisisobutyronitrile (AIBN) or 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPC) is 0.1-5 mol%.

1.2 Synthesis procedure for copolymers

For the synthesis of polymers P1 to P19 and AP1 to AP5, the corresponding monomers, the initiator and, if necessary, the chain transfer agent (CTA) were dissolved in methanol (2-5 ml, applies to P1-P17 and AP2-AP4) or a water/1,4-dioxane mixture (V/V = 3:7, 2-5 ml, applies to P18, P19, AP1 and AP5) in a 10 ml Schlenk flask. The specific reactants and their amounts can be found in Table 2. The reaction mixture was degassed by flushing with argon (30 min). The reaction vessels were placed in a preheated oil bath (65 °C) or a preheated aluminum block (65 °C) for 16 to 24 hours. The reaction was stopped by cooling with liquid. nitrogen and exposure of the mixture to oxygen. The polymers were precipitated at least twice in ice-cold ethyl acetate (200 ml), then filtered or centrifuged and dried overnight in vacuo.

In the case of polymers P1, P2, P8 and P9, the isolated polymer was taken up in water (2.5 ml) and deprotected by adding trifluoroacetic acid (0.5 ml). The mixture was stirred at room temperature overnight and then precipitated in ice-cold tetrahydrofuran (200 ml). The precipitate was filtered off and stirred with the cationic anion exchange resin Lewatit MP62 for 24 hours. The anion exchanger was then filtered off and the filtrate was dried by lyophilization. Table 2 No . Monomer(s) A ₁ /R ₁ Name / mg / (mmol) Monomer A ₂ /R ₂ Name / mg / (µmol) Monomer A ₃ /R ₃ Name / mg / (µmol) Monomer A ₄ /R ₄ Name / mg / (mmol) CTA Name / mg / (µmol) Initiator Name / mg / (µmol) P1 HEAm -- BPAm -- APAm-Boc DMP AIBN 362 16.61 38.0 6.02 2.80 (3.14) (66.2) (16.6) (17.0) (17.4) P2 HEAm -- BPAm -- AEAm-Boc DMP AIBN 364 16.72 36.0 6.06 2.80 (3.16) (66.6) (17.0) (17.0) (17.4) P3 HEAm HPAm BPAm -- -- DMP AIBN 289 110 17.2 6.12 2.80 (2.51) (0.85) (67.4) (16.8) (17.4) P4 HEAm HPAm BPAm -- -- DMP AIBN 198 212 16.73 6.28 2.80 (1.72) (1.73) (65.6) (17.3) (17.4) P5 -- HPAm BPAm -- APAm-Boc DMP AIBN 366 15.07 34.0 5.44 2.40 (2.83) (60.0) (14.8) (15.0) (15.0) P6 -- HPAm/ BPAm -- AEAm-Boc DMP AIBN 367 15.07 32.0 5.46 2.40 (2.84) (60.0) (15.0) (15.0) (15.0) P7 HPAm HEAm BPAm -- -- DMP AIBN 308 97 16.23 5.86 2.80 (2.38) (0.84) (63.6) (16.1) (17.4) P8 HEAm -- BPAm -- AaAm DMP AIBN 377 17.33 22.0 6.28 2.80 (3.27) (69.0) (17.0) (17.3) (17.4) P9 -- HPAm BPAm -- AaAm DMP AIBN 380 15.58 20.0 5.63 2.50 (2.94) (61.8) (15.0) (15.5) (15.5) P10 HEAm -- BPQAAm -- -- -- AIBN 500 38.2 3.64 (4.34) (88.6) (22.2) P11 HEAm HPAm BPAm -- -- -- AIBN 500 182 29.5 4.82 (4.34) (1.41) (117) (29.3) P12 HEAm HPAm BPQAAm -- -- -- AIBN 212 198 28.3 2.91 (1.73) (1.72) (65.6) (17.7) P13 -- HPAm BPQAAm -- -- -- AIBN 400 26.7 2.59 (3.10) (62.0) (15.8) P14 HEAm HPAm BPQAAm -- — -- AIBN 289 110 29.1 2.82 (2.51) (0.85) (67.4) (17.2) P15 HEAm -- BPAm -- -- -- AIBN 500 22.3 3.64 (4.34) (88.6) (22.2) P16 -- HPAm BPAm -- -- -- AIBN 400 15.58 2.50 (3.10) (62.0) (15.5) P17 HEAm HPAm BPAm -- -- -- AIBN 212 198 16.73 2.80 (1.73) (1.72) (65.6) (17.4) P18 HEAm -- BPAm VPA -- EMP AIPC 200 29.1 50.0 2.60 3.75 (1.74) (116) (463) (11.6) (11.6) P19 HEAm -- BPAm VPA -- -- AIPC 200 29.1 50.0 3.75 (1.74) (116) (463) (11.6) AP1 HEAm -- -- VPA -- -- AIPC 200 46.9 3.52 (1.74) (434) (10.9) WP2 HEAm -- -- VPA -- -- AIBN 200 20.8 1.64 (1.74) (193) (8.88) WP3 HEAm -- -- VPA -- -- AIBN 200 9.87 1.64 (1.74) (91.4) (8.88) AP4 HEAm -- -- VPA -- -- AIBN 200 3.84 1.64 (1.74) (35.5) (8.88) AP5 HEAm -- -- VPA -- EMP AIPC 200 46.9 2.45 3.52 (1.74) (434) (10.9) (10.9)

Dispersität Ð P1 92% 34.6 kg/mol 1.33 P2 98% 33.3 kg/mol 1.18 P3 83% 34.9 kg/mol 1.23 P4 73% 39.4 kg/mol 1.19 P5 76% 14.5 kg/mol 1.13 P6 78% 10.9 kg/mol 1.18 P7 66% 36.3 kg/mol 1.36 P8 67% 31.9 kg/mol 1.25 P9 66% 34.0 kg/mol 1.38 P10 83% 40.4 kg/mol 3.83 P11 82% 69.3 kg/mol 3.78 P12 76% - - - - P13 88% - - - - P14 91% - - - - P15 79% 52.4 kg/mol 3.21 P16 79% - - - - P17 75% - - - - P18 65% -- -- P19 85% -- -- AP1 60% -- -- AP2 85% -- -- AP3 85% -- -- AP4 83% -- -- AP5 73% -- -- With CTA = chain transfer agent, HEAm = N-(2-hydroxyethyl)acrylamide, HPAm = N-(2-hydroxypropyl)acrylamide, BPAm = N-(4-benzoylphenyl)acrylamide, BPQAAm = [(4-benzoylphenyl)methyl]dimethyl[3-(prop-2-enamido)-propyl]ammonium bromide, VPA = vinylphosphonic acid, APAm-Boc = N-tert-butyloxycarbonyl-(N'-3-aminopropyl)acrylamide, AEAm-Boc= N-tert-butyloxycarbonyl-(N'-3-aminoethyl)acrylamide, DMP = 2-{[(dodecylthio)carbothioyl]-thio}-2-methylpropanoic acid, EMP = 2-{[(ethylthio)carbothioyl]-thio}-2-methylpropanoic acid, AIBN = azobis(isobutyronitrile), AIPC = 2,2'-Azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride. Table 3 Polymer abbreviation yield Number average molar mass $\overline{M_n}$

Dispersity Ð P1 92% 34.6 kg/mol 1.33 P2 98% 33.3 kg/mol 1.18 P3 83% 34.9 kg/mol 1.23 P4 73% 39.4 kg/mol 1.19 P5 76% 14.5 kg/mol 1.13 P6 78% 10.9 kg/mol 1.18 P7 66% 36.3 kg/mol 1.36 P8 67% 31.9 kg/mol 1.25 P9 66% 34.0 kg/mol 1.38 P10 83% 40.4 kg/mol 3.83 P11 82% 69.3 kg/mol 3.78 P12 76% - - - - P13 88% - - - - P14 91% - - - - P15 79% 52.4 kg/mol 3.21 P16 79% - - - - P17 75% - - - - P18 65% -- -- P19 85% -- -- AP1 60% -- -- WP2 85% -- -- WP3 85% -- -- AP4 83% -- -- AP5 73% -- --

2. Coating process

1. 1. Sandwichaufbau: Das Titansubstrat wird in einer Lösung des Ankerpolymers inkubiert, welches aus Hauptmonomer und Ankermonomer besteht. In einem zweiten Schritt wird eine Lösung des Beschichtungspolymers bestehend aus Hauptmonomer und Vernetzermonomer durch ein einfaches Verfahren (Beispiel: Sprühen oder Eintauchen) aufgetragen und eingetrocknet. Die Vernetzung der trockenen Polymerschichten wird durch Bestrahlung mit UV-Licht induziert und simultan das Implantat sterilisiert.
2. 2. Einschichtsystem: Das Titansubstrat wird in einer Lösung des Polymers inkubiert, welches aus Hauptmonomer, Ankermonomer und Vernetzermonomer besteht, und anschließend getrocknet. Die Vernetzung der trockenen Polymerschicht wird durch Bestrahlung mit UV-Licht induziert und simultan das Implantat sterilisiert.

Two different strategies are used for the coating process, which can be carried out with polymers of different combinations of the above-mentioned monomer species.

1. 1. Sandwich structure: The titanium substrate is incubated in a solution of the anchor polymer, which consists of the main monomer and anchor monomer. In a second step, a solution of the coating polymer consisting of the main monomer and crosslinking monomer is applied and dried using a simple process (e.g. spraying or dipping). The crosslinking of the dry polymer layers is induced by irradiation with UV light and the implant is simultaneously sterilized.
2. 2. Single-layer system: The titanium substrate is incubated in a solution of the polymer, which consists of the main monomer, anchor monomer and crosslinker monomer, and then dried. The crosslinking of the dry polymer layer is induced by irradiation with UV light and the implant is simultaneously sterilized.

1. 1. Für den Sandwichaufbau wurden Stammlösungen der Polymere P1 bis P17 in einer Wasser/Ethanol-Mischung (70:30 V/V) mit einer Konzentration von 25 mg·ml^-1 hergestellt. Auf die Substrate wurden dann 200 µl der zu testenden Polymerlösung gegeben und diese im Vakuumofen (10 mbar, 40°C) eingedampft. Daraufhin wurden die Scheiben für eine Stunde mit UV-Licht einer Wellenlänge von 254 nm bestrahlt. Die beschichteten Substrate wurden durch Inkubation in Wasser für mehrere Stunden gewaschen und abschließend im Vakuumofen (10 mbar, 40°C) getrocknet.
2. 2. Für das Einschischtsystem (Polymere P18 und P19) wurden die Scheiben für eine Stunde mit UV-Licht einer Wellenlänge von 254 nm bestrahlt, die beschichteten Substrate durch Inkubation in Wasser für mehrere Stunden gewaschen und abschließend im Vakuumofen (10 mbar, 40°C) getrocknet.
3. 3. Zelladhäsions- und Bakterientests

Coating procedure: The titanium disks for cell adhesion tests were stirred overnight in an aqueous Hellmanex solution (1-3%). The disks were then rinsed with plenty of water and ethanol and dried in a nitrogen stream. The dried titanium substrates were treated with a corona discharger and immediately immersed in water. They were then incubated overnight in aqueous solutions of the monolayer polymer (P18, P19) or the anchor polymer (1-10 mg·ml ^-1 ). The disks were dried in a vacuum oven (10 mbar, 40°C) after rinsing with water and ethanol.

1. 1. For the sandwich structure, stock solutions of the polymers P1 to P17 were prepared in a water/ethanol mixture (70:30 V/V) with a concentration of 25 mg·ml ^-1 . 200 µl of the polymer solution to be tested were then added to the substrates and evaporated in a vacuum oven (10 mbar, 40°C). The discs were then irradiated with UV light with a wavelength of 254 nm for one hour. The coated substrates were washed by incubating in water for several hours and then dried in a vacuum oven (10 mbar, 40°C).
2. 2. For the single-layer system (polymers P18 and P19), the discs were irradiated with UV light of a wavelength of 254 nm for one hour, the coated substrates were washed by incubation in water for several hours and finally dried in a vacuum oven (10 mbar, 40°C).
3. 3. Cell adhesion and bacterial tests

Before cell and bacterial testing, the cytotoxicity of the polymers was determined analogously to ISO 10993-5 -Standard (Biological evaluation of medical devices - In vitro cytotoxicity testing). These tests showed that the polymers used do not have any cytotoxic effect.

In a first cell experiment, primary fibroblasts or tenocytes were seeded on cell culture plates partially coated with polymer. shows using the example of tenocytes that the cells grow exclusively on the uncoated part of the plate. There is no adhesion of the cells on the part coated with polymer. No cell adhesion could be detected on fully coated plates either, but it was shown that the non-adherent cells are vital, as they adhered and proliferated after being transferred to a cell culture plate.

The polymer was then applied to titanium disks as previously described and cell adhesion was examined. shows that no cell adhesion occurs on the polymer-coated titanium surface. shows the adhesion of cells on an uncoated titanium plate. As with the coated cell culture surface, it was shown that the non-adherent cells are also vital, as they adhered and proliferated after being transferred to an uncoated titanium plate.

The bacterium that is mainly responsible for infections in the area of bone osteosynthesis is Staphylococcus aureus. Therefore, this bacterial strain was diluted in medium and applied to the polymer layers. After 24 hours, the medium was seeded in different dilutions on agar plates and the CFU (colony forming units) were detected. In the control, which was incubated on a plate with a non-antibacterial polymer, a high number of CFUs can be seen ( , whereas no CFUs were detected on the sample incubated on a plate coated with an antibacterial polymer ( , which indicates a significant antimicrobial effect of the corresponding polymers. Table 3: Evaluation of cell adhesion tests Polymer abbreviation Cell type No growth No cytotoxicity No bacterial growth P1 Fibroblasts +++++ +++++ P1 Tenocytes ++++ +++++ P2 Fibroblasts +++++ + P3 Fibroblasts ++++ to +++++ ++ P4 Fibroblasts ++++ to +++++ + P4 Tenocytes ++ + P5 Fibroblasts ++++ +++++ P6 Fibroblasts + +++++ P7 Fibroblasts +++++ + P7 Tenocytes ++++ ○ P8 Fibroblasts ++++ ○ P9 Fibroblasts ++ ++ ○ P10 Fibroblasts +++++ +++++ Staph. aureus +++++ P10 Tenocytes ++++ +++++ P11 Fibroblasts +++++ +++++ P11 Tenocytes ○ +++++ P12 Fibroblasts +++++ +++++ P12 Tenocytes +++++ +++++ P14 Fibroblasts +++ +++++ P14 Tenocytes ++++ +++++ P15 Fibroblasts ○ +++++ Staph. aureus ○ P15 Tenocytes ++++ +++++ P16 Fibroblasts + +++++ P16 Tenocytes ++++ +++++

Rating from o to +++++ (o = higher cell/bacterial growth or higher cytotoxicity and +++++ = lower cell/bacterial growth or lower cytotoxicity).

In summary, the coatings were able to successfully prevent adhesion of fibroblasts (the main cell type of human connective tissue) and tenocytes (characteristic cell of the human tendon) without having a cytotoxic effect on them. In addition, an antibacterial effect of special polymer structures was demonstrated.

credentials

• [1] CA Jeffrey, A medical implant and a method of coating a medical implant, WO2018107243 A1 , Dec 15, 2017.
• [2] AP Shete, AA Nisal, AK Lele, A process for coating a biomedical implant with a biocompatible polymer and a biomedical implant therefrom, WO2018173074 A1 , Mar 23, 2018.
• [3] Y. Lee, SA Kang, TH Choi, JU Park, SA Kim, et al., Method for coating implant using heat, WO2020231073 A1 , May 07, 2020.
• [4] H.-E. Kim, S.-M. Lee, J. Kim, SM Chung, Method for manufacturing hydroxyapatite-coated zirconia implant by means of dip coating using hydroxyapatite sol, WO2020204254 A1 , May 15, 2019.
• [5] HD Link, Method for producing an implant coating and corresponding implant, WO2012163950 May 30, 2012.
• [6] H.-G. Neumann, C. Prinz, Antibacterial and osteoinductive implant coating, method of producing such coating, and implant coated with same, EP2617439 B1 , Jan 15, 2013.
• [7] E. Wintermantel, S.-W. Ha, Springer, Medical Technology - Life Science Engineering, 2008, DOI: 10.1007/978-3-540-74925-7 .
• [8th] NG Grün, N. Donohue, P. Holweg, A.-M. Weinberg, J. Miner. Metabolic. Musculoskeletal. Diseases, (25), 82-89, Resorbable implants in trauma surgery, 2018, DOI: 10.1007/s41970-018-0041-6 .

QUOTES INCLUDED IN THE DESCRIPTION

This list of documents listed by the applicant was generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions.

Cited patent literature

• WO 2018107243 A1 [0153]
• WO 2018173074 A1 [0153]
• WO 2020231073 A1 [0153]
• WO 2020204254 A1 [0153]
• WO 2012163950 [0153]
• EP 2617439 B1 [0153]

Cited non-patent literature

• ISO 10993-5 [0148]
• E. Wintermantel, S.-W. Ha, Springer, Medical Technology - Life Science Engineering, 2008, DOI: 10.1007/978-3-540-74925-7 [0153]
• N. G. Grün, N. Donohue, P. Holweg, A.-M. Weinberg, J. Miner. Metabolic. Musculoskeletal. Diseases, (25), 82-89, Resorbable implants in trauma surgery, 2018, DOI: 10.1007/s41970-018-0041-6 [0153]

Claims (31)

Polymer having a structure of the general formula (I)

wherein A ₁ is -H or -CH ₃ ; A ₂ is -H or -CH ₃ ; A ₃ is -H or -CH ₃ ; A ₄ is -H or -CH ₃ ; R ₁ , for each repeating unit, is independently selected from the group consisting of

R ₂ , for each repeating unit, is independently selected from the group consisting of

wherein each "spacer" is independently selected from the group consisting of linear or branched alkyl chains and linear or branched ethylene or propylene oxide chains, preferably independently selected from linear or branched C _1-20 alkyl chains; R _x , each independently, is -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (eg -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and R _y , each independently, is -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; R ₃ , for each repeating unit, is independently selected from the group consisting of

wherein n ₃ , n ₄ , n ₅ , n ₆ and n ₇ are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18; R ₄ , for each repeating unit, is independently selected from the group consisting of

Y is a fragment A of a chain transfer reagent or an end group; and Z is a fragment B of the chain transfer reagent or an end group. Polymer according to Claim 1 , wherein R ₁ , for each repeating unit, is independently selected from the group consisting of

Polymer according to Claim 1 or 2 , wherein R ₂ , for each repeating unit, is independently selected from the group consisting of

wherein n ₁ and n ₂ are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20; R _x is each independently -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and R _y , each independently, is -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano. Polymer according to Claim 1 or 2 , wherein R ₂ , for each repeating unit, is independently selected from the group consisting of

Polymer according to one of the Claims 1 until 4 , wherein R ₃ , for each repeating unit, is independently selected from the group consisting of

where n ₃ , n ₄ , n ₅ , n ₆ and n ₇ are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18. Polymer according to one of the Claims 1 until 4 , where R ₃ , for each repeating unit,

is. Polymer according to one of the Claims 1 until 6 , where R ₄ , for each repeating unit,

is. Polymer according to one of the Claims 1 until 7 , where A ₁ , A ₂ , A ₃ and A ₄ are each -H. Polymer according to Claim 1 , wherein R ₁ , for each repeating unit, is independently selected from the group consisting of

R ₂ , for each repeating unit, is independently selected from the group consisting of

R ₃ , for each repeat unit,

and R ₄ , for each repeating unit, is independently selected from the group consisting of

Polymer according to Claim 9 , where A ₁ is -H, A ₂ is -H, A ₃ is -H, and A ₄ is -H. Polymer according to one of the Claims 1 until 10 , where Y

is, and Z

wherein n ₈ is an integer from 1 to 24, preferably an integer from 1 to 14, more preferably an integer from 1 to 11; most preferably 1 or 11. Polymer according to one of the Claims 1 until 10 , where Y and Z are each an end group. Polymer according to one of the Claims 1 until 12 , where X _[2] is 0 and x _[3] is >0 to <1; and optionally x _[4] is >0 to <1. Polymer according to one of the Claims 1 until 12 , where X _[2] is >0 to <1 and x _[3] is 0; and optionally x _[4] is >0 to <1. Polymer according to one of the Claims 1 until 12 , where X _[2] is >0 to <1 and x _[3] is >0 to <1; and optionally x _[4] is >0 to <1. Polymer according to Claim 1 , selected from the group consisting of

where n is an integer from 2 to 100,000, such as an integer from 50 to 10,000, e.g. an integer from 100 to 2,000. A hydrogel comprising a cross-linked polymer according to any one of Claims 1 until 16 . Coating comprising at least one layer comprising a polymer according to one of the Claims 1 until 16 includes. Coating according to Claim 18 comprising a first layer comprising a polymer according to Claim 13 and a second layer comprising a polymer according to Claim 14 includes. Coating according to Claim 18 , which comprises a layer comprising a polymer according to Claim 15 includes. Metal-containing substrate, characterized in that at least part of its surface is covered with a coating comprising at least one layer containing a polymer according to one of the Claims 1 until 16 includes. Substrate according to Claim 21 , wherein the substrate comprises or consists of titanium or a titanium alloy, preferably wherein the titanium or titanium alloy comprises a titanium oxide. Device comprising a substrate according to Claim 21 or 22 . Device according to Claim 23 , wherein the device is a medical device. Device according to Claim 24 , wherein the medical device is an implant. Use of a device according to Claim 25 as a short-term implant. Use of the polymer according to one of the Claims 1 until 16 as an anti-adhesive coating, preferably as an anti-adhesive coating on a medical device, further preferably as an anti-adhesive coating on an implant. Monomer having a structure of the general formula (II)

wherein each "spacer" is independently selected from the group consisting of linear or branched alkyl chains and linear or branched ethylene or propylene oxide chains, preferably independently selected from linear or branched C _1-20 alkyl chains; R _x , each independently, -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (eg -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and R _y is, each independently, -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. -CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano. Monomer according to Claim 28 , having a structure of the general formula (Ila)

wherein n _x and n _y are independently an integer from 1 to 20; R _x is, each independently, -H, -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. - CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl, -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano; and R _y , each independently, is -H, -OH, halogen (Br, Cl, I, or F), halogen-C _1-4 alkyl (e.g. - CF ₃ , -CCL ₃ , -CBr ₃ , -Cl ₃ ), -NH ₂ , -C _1-4 alkyl, -C _2-4 alkenyl, -C _2-4 alkynyl, -OC _1-4 alkyl, -OC _2-4 alkenyl, -OC _2-4 alkynyl -NO ₂ , -SH, -SO ₂ H, -SO ₃ H, -NCS, -SCN, -COOH or cyano. Monomer according to Claim 28 or 29 , which has the following structure.

Use of a monomer according to one of the Claims 28 until 30 as photocrosslinkers.