Material comprising a peptide having Anti-biofouling properties

Abstract

The present patent application describes a material made from a peptide having anti-biofouling properties, the method for the preparation thereof, and the possible applications thereof.

Description

[0001] "Material comprising a peptide having anti-biofouling properties"

[0002] DESCRIPTION

[0003] The bacterial colonization of biomedical devices is a highly critical phenomenon, which can lead to the malfunction of the devices themselves, as well as the possible development of infections in the patient.

[0004] The use of these indispensable devices is thus associated with a technical problem of high severity in the medical and surgical field, which concerns the possibility of infection for patients and contamination of the hospital environment.

[0005] Currently, the suggested approaches for producing biomaterials resistant to microbial contamination involve either a postproduction functionalization step or the inclusion of antimicrobials .

[0006] In the first case, the post-functionalization requires the use of synthetic polymer species and a multi-step production of the biomaterial, which increase the costs and environmental risk related to the production thereof.

[0007] The use of antimicrobials in the coatings of biomedical devices, although effective, can in turn lead to the formation of resistance mechanisms of the bacteria involved, potentially worsening the risk of severe infection and resistance to possible treatments in patients.

[0008] Finally, the presence of metal nanoparticles, as an additive in biomaterials, has shown good efficacy in preventing the formation of bacterial biofilms, but the use of such nanostructures in clinical practice is still very limited, making this option hardly usable in the short term.

[0009] The prior art document CN110354315 describes a method for preparing a three-dimensional antibacterial porous silk fiber / graphene / titanium dioxide.

[0010] The prior art document CN109513039 describes an antibacterial hydrogel containing imidazole and the use thereof in dressings.

[0011] The prior art document WO 2018 / 074951 describes macroporous functional biomaterials based on natural biopolymers, and more in particular macroporous protein sponges which have antibacterial activity and can be used for biomedical purposes.

[0012] The prior art document CN105017537 describes a biological material usable for the regenerative repair of tissues, in particular a copolymerized composite biological material of gelatin and polyester and a preparation method thereof.

[0013] The prior art document WO 2019 / 116342 describes an oligopeptide of formula SJXXZGXP, in which S is a serine residue, J is a serine residue or is absent, X is independently any amino acid, Z is selected from a tyrosine, histidine, phenylalanine or tryptophan residue, G is a glycine residue and P is a proline residue, characterized in that at least the Z residue is replaced by at least one halogen selected from bromine, chlorine or iodine, characterized by elastomeric properties.

[0014] Summary of the invention

[0015] The inventors of the present patent application have surprisingly found that it is possible to make materials based on biomolecules capable of resisting bacterial contamination. The materials (scaffolds) thus obtained do not require further chemical manipulation to acquire antimicrobial properties.

[0016] Object of the invention

[0017] In a first object, the present invention describes a process for preparing an antibacterial material.

[0018] The antibacterial material obtained is a further object of the invention.

[0019] In a second object, the present invention describes biomedical devices obtained with the described antibacterial material.

[0020] In a third object, the present invention describes the use of the antibacterial material for making biomedical devices.

[0021] Brief description of the drawings

[0022] Figure 1 shows the chemical structure of the peptides SDSY(3,5- Br)GAP and SDSYGAP. The hydrogen atoms are replaced by bromine atoms in the ortho position with respect to the OH group of the aromatic ring of tyrosine.

[0023] Figure 2 shows the scanning electron microscopy (SEM) images of the electrospun (a) and crosslinked (b) composite samples for the different ratios of SDSY (3,5-Br)GAP and gelatin studied. Bromine distribution maps obtained from elemental analysis, single or superimposed on the corresponding SEM images (c,d).

[0024] Figure 3 shows (a) Degrees of crosslinking of the different scaffolds, (b) Mass losses recorded after 8, 24 and 48 hours in PBS lx at 37°C for the different scaffolds. After 48h, the mass loss seems to stabilize for all ratios observed, even after 7 days. Figure 4 shows the SEM images of the freeze-dried scaffolds after 24h immersion in lx PBS at 37°C (a: 100% gelatin, b: 70% Res (Br), c: bromine distribution map corresponding to b).

[0025] Figure 5 shows optical microscope images of gelatin-only (a), 70% SDSY (3,5-Br)GAP (b), 30% SDSY (3,5-Br)GAP, or 30% SDSYGAP (d) samples after 14 days incubation in DMEM with 10% Fetal Calf Serum.

[0026] Figure 6 shows the stress-strain curve of electrospun scaffolds based on 100% gelatin, 70% SDSYGAP (RW7) and 70% SDSY (3,5Br)GAP (RB7).

[0027] Figures 7b-e show the comparison of the values of tensile strength and elongation at break for all different ratios of gelatin / SDSYGAP and gelatin / SDSY (3,5Br)GAP.

[0028] Figures 8f-h show f) 100% gradual cycle tensile tests of gelatin, RW7 and RB7, with corresponding recovery ratio values (g) and resilience values (h). * p<=0.05 ** p<=0.01 * ** p<=0.001 indicates a significant difference between the groups.

[0029] Figure 9 shows the graph of weight loss of electrospun scaffolds after incubation with 0.01 U / mL protease XIV solution in PBS pH 7.4.

[0030] Figure 10 shows a) the percentage of inhibition of ABTS cationic radicals when incubated with electrospun scaffolds at time zero, after 30 minutes and after 60 minutes, b) Reduction capacity of ferric ion Fe3+to ferrous ion Fe2+by electrospun scaffolds expressed as equivalents (mM) of vitamin C.

[0031] Detailed description of the invention

[0032] In a first object, the present invention describes a process for preparing an antibacterial material. For the purposes of the present invention, the antibacterial material described is a biomaterial.

[0033] This means that said biomaterial comprises a peptide and in particular the peptide of formula I:

[0034] SJXXZGXP (SEQ ID n. 1) wherein S is a serine residue, J is a serine residue or is absent, X is independently any desired amino acid, Z is an amino acid residue selected from: tyrosine, histidine, phenylalanine or tryptophan, G is a glycine residue and P is a proline residue, in which at least the Z residue is modified with at least one halogen selected from: Br, Cl, I.

[0035] In a first embodiment, in formula (I) above, SJXXZGXP, S is a serine residue, J is absent, X is independently any desired amino acid, Z is a residue of an amino acid selected from: tyrosine, histidine, phenylalanine, or tryptophan, G is a glycine residue, and P is a proline residue, in which at least the Z residue is modified with at least one halogen selected from: Br, Cl, I (SEQ ID n.2).

[0036] In a further embodiment, in said oligopeptide SJXXZGXP S is a serine residue, J is absent, X is independently any desired amino acid, Z is a tyrosine residue, G is a glycine residue and P is a proline residue, in which at least the Z residue is modified with at least one halogen selected from: Br, Cl, I (SEQ ID n. 3).

[0037] In a further embodiment, in said oligopeptide SJXXZGXP S is a serine residue, J is a serine residue or is absent, X is independently any desired amino acid, Z is a tyrosine residue, G is a glycine residue and P is a proline residue, in which the phenolic group on said tyrosine residue Z is mono- or di-ortho-halogenated, preferably is di-ortho-brominated (SEQ ID n. 4).

[0038] In a further embodiment, in said oligopeptide SJXXZGXP S is a serine, J is absent, X is independently any desired amino acid, Z is a histidine, G is a glycine and P is a proline, in which the imidazole on said histidine Z is mono- or di-halogenated, preferably is di-brominated (SEQ ID n. 5).

[0039] In a further embodiment, in said oligopeptide SJXXZGXP S is a serine residue, J is absent, X is independently any desired amino acid, Z is a phenylalanine residue, G is a glycine residue and P is a proline residue, in which the phenyl on said phenylalanine residue Z is mono para-halogenated, in which the halogen is preferably iodine (SEQ ID n. 6).

[0040] In a further embodiment, in said oligopeptide SJXXZGXP S is a serine residue, J is absent, X is independently any desired amino acid, Z is a tryptophan residue, G is a glycine residue and P is a proline residue, in which the indole on said tryptophan residue Z is mono- or di-halogenated, preferably is di-brominated (SEQ ID n. 7).

[0041] In a further embodiment, said oligopeptide is SDSY *GAP in which S is a serine residue, D is an aspartic acid residue, Y is a tyrosine residue, G is a glycine residue, A is an alanine residue and P is a proline residue, in which * is indicative of said tyrosine residue being mono- or di-halogenated, preferably di-brominated, even more preferably di-ortho-brominated, i.e., it is SDS-Y(3,5 Br)-GAP (SEQ

[0042] ID n. 8). In a preferred aspect of the invention, the peptide employed has the formula:

[0043] SDS-Y(3,5 Br)-GAP (SEQ ID n. 8) wherein the tyrosine residue is replaced by two Br in the ortho position (as shown in Figure 1).

[0044] In the following description, such a heptapeptide will be referred to as "Res-Br" or SDSY(3,5 Br)GAP.

[0045] For the purposes of the present invention, such a process comprises the steps of:

[0046] 1) preparing a solution comprising the peptide of the invention, and

[0047] 2) electrospinning the solution obtained from step 1).

[0048] For the purposes of the present invention, a solution comprising a peptide as described above is prepared in step 1).

[0049] According to a preferred aspect of the present invention, said peptide is the heptapeptide "Res-Br".

[0050] In the following description, wherein reference is made to the heptapeptide "Res-Br", a peptide of formula (I) can also be understood as described above, wherein the heptapeptide "Res-Br" is a preferred aspect.

[0051] In particular, the solution prepared is an aqueous solution and preferably is a solution of water and acetic acid.

[0052] In a first aspect of the present invention, the prepared solution can comprise only the above-described peptide.

[0053] In a preferred aspect of the present invention, the prepared solution comprises a mixture of the peptide and another material or biomaterial. Other materials or biomaterials which can be used for the purposes of the present invention can be chosen from materials and biomaterials of a protein nature, such as: gelatin, collagen, fibroin, sericin, elastin, keratin.

[0054] In a particularly preferred aspect of the present invention, the solution prepared comprises the peptide of formula (I) according to the present invention and gelatin.

[0055] In an even more preferred aspect, said peptide is the heptapeptide "Res-Br".

[0056] The peptide of formula (I) (or heptapeptide "Res-Br") of the invention and gelatin can be mixed together in a ratio between 1:9 and 9:1, wherein a ratio from 3:7 to 7:3 is particularly preferred.

[0057] The heptapeptide or mixture of heptapeptide with another material or biomaterial is dissolved in the aqueous solution in a concentration of about 20-40% (m / v), wherein 30% is particularly preferred.

[0058] As per step 2) of electrospinning, this is carried out according to techniques known in the art, optimized based on the peptide content to modulate the size of the nanofibers obtained.

[0059] In a preferred aspect, the electrospinning step is carried out at room temperature, i.e., about 22-25°C.

[0060] In a preferred aspect, the electrospinning is carried out under relative humidity conditions between 28-34%.

[0061] According to an optional aspect of the process of the invention, a step 3) of crosslinking the product obtained by electrospinning can be then carried out. Said crosslinking step can be carried out by treating, for example in a bath, the electrospun matrix with a solution of carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in acetonitrile and ethanol.

[0062] If necessary, the pH of the crosslinking bath can be brought to pH=8, for example by addition of NaOH.

[0063] In a preferred aspect, the duration of the crosslinking step can be up to 10 hours, preferably 8 hours.

[0064] In a preferred aspect, the temperature of the crosslinking step can be 4°C.

[0065] After the crosslinking step, the electrospun matrix is treated and subjected to one or more rinsing steps to eliminate the solvents.

[0066] After washing, the electrospun and crosslinked matrix is suitably dried.

[0067] Alternatively to step 2) of electrospinning, a three- dimensional printing step (3D printing) can be carried out.

[0068] The present invention also relates to the antibacterial material obtained according to the process described above.

[0069] Such a material is characterized in that it has excellent mechanical and antibacterial properties, as well as a high stability of the same properties over time, as demonstrated in the experimental section hereinbelow.

[0070] In an aspect of the invention, said material is in the form of fibers.

[0071] In a preferred aspect, said fibers have a diameter of about 400-600 nm and preferably about 500-600 nm. In a second object, the present invention describes biomedical devices obtained from the antibacterial material described above.

[0072] In particular, devices which can be made include: prostheses, vascular stents, membranes, implantable devices, or parts or portions of such devices.

[0073] Biocompatible parts of electronic devices can also be made from the described material.

[0074] In accordance with a third object of the invention, the use of the material made as described above for producing biomedical devices is also described.

[0075] Such devices include: prostheses, vascular stents, membranes, implantable devices, or parts or portions of such devices.

[0076] The use of the described material is also for making biocompatible electronic devices or parts thereof.

[0077] The present invention will be further described in the following experimental section.

[0078] Experimental section

[0079] Materials

[0080] The reagents and solvents were used as received without further purification and purchased with purity >97%. In particular, the gelatin (type A, porcine origin, Bloom 300g) was purchased from Sigma Aldrich, while the peptides were synthesized by Biofab Research (Rome, Italy) by solid state synthesis. The integrity of the peptides was verified by mass spectroscopy and the purity thereof (>98%) by reversed-phase high performance liquid chromatography.

[0081] Electrospinning procedure Different ratios of gelatin and peptide (3:7, 5:5, 7:3 w / w} were dissolved in a mixture of acetic acid and water (9:1) at a concentration of 30% m / v. The solution was left stirring at room temperature until complete solubilization and then transferred into 5 mL syringes. The syringes were positioned in a syringe pump (KD Scientific, Model 100, Holliston, MA, USA), with a flow rate set between 200 pL / h and 300 pL / h, and connected to 21G stainless steel needles (I.D. 0.514 mm). The solution was electrospun towards flat collectors made of aluminum or glass covered with indium-tin oxide (10 cm x 10 cm), obtaining a random orientation of the fibers. The needle-collector distance was set to 12 cm and the applied voltage to 12.6 kV. The electrospinning process was carried out at room temperature (22°C-25°C) with relative humidity between 28% and 34%. The correct deposition and homogeneity of the nanofibers was confirmed by scanning electron microscopy analysis (Zeiss EVO 50 EP, 1-1.5kV), following the deposition of a thin coating of gold on the surface of the samples. The diameters of the nanofibers thus obtained were found to be 400-600 nm, with slightly higher values, within these ranges, for the samples containing more gelatin (Res (Br):gelatin 3:7) (Figure 2A).

[0082] Crosslinking procedure

[0083] With the aim of increasing the stability of the electrospun samples in aqueous solutions, a crosslinking procedure was devised in the presence of l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). In particular, a 50 mM EDC / 20 mM NHS solution (2.5:1 molar ratio) in acetonitrile and ethanol (1:1 v / v) was prepared, in which the electrospun matrix was then immersed. In order to limit the coalescence of the nanofibers during the crosslinking process, the matrices were partially constrained to the sides to keep them taut. For the samples containing a higher percentage of gelatin (Res(Br):gelatin 3:7), the pH of the solution was adjusted after 10 minutes, bringing it to pH 8 by adding 0.1% 10M NaOH solution. For all the electrospun fibers, the crosslinking procedure occurred at 4°C for 8 hours. The matrices were then removed from the reaction bath and subjected to three consecutive washes with the same solvents used for crosslinking (CHsCNiEtOH 1:1 v / v). Finally, the crosslinked matrices were moved into a dryer containing calcium chloride to allow a controlled evaporation of the solvent for at least 12 hours. Following crosslinking, fibrillar morphology was preserved, with negligible increases in nanofiber diameters (Figure 2B). Furthermore, the presence and distribution of the brominated peptide within the fibers was verified by elemental analysis using Bruker XFlash 6130 probe (resolution: 123 eV at Mn Ka, 45 eV at C Ka and 53 eV at F Ka) (Figures 2C,2D).

[0084] Assessment of the scaffold crosslinking degree and stability at physiological pH

[0085] The degree of crosslinking was measured by quantifying the number of free amines present in the crosslinked samples with respect to those not crosslinked by means of trinitrobenzenesulfonic acid (TNBS) assay. In particular, 2-3 mg of electrospun fiber was immersed in 0.5 mL NaHCOs pH 8.5, to which 0.5 mL of 0.25% m / v TNBS solution was added. The solution was heated at 40°C for two hours and then brought to 60°C for an hour and a half after adding 1 mL 6 M HC1. 100 pL of the solution was then transferred to a quartz cuvette and diluted with MilliQ water to 1 mL. The absorbance of the solution was measured at 346 nm with a Jasco V-630 double beam spectrophotometer, using as blank a solution prepared as in the previous steps but without adding the sample. The degree of crosslinking was calculated by comparing the absorbance at 346 nm of the crosslinked samples with those not crosslinked, obtaining values between 70% and 95%. The samples with higher SDSY (3,5-Br)GAP content achieved higher cross-linking values (Figure 3A). The stability of the scaffolds thus obtained was evaluated in lx PBS (pH 7.4) at 37°C for a total period of 7 days. The observed mass losses were found to be between 10% ± 2.7% and 20% ± 4.8% for the matrices containing 70% and 30% SDSY (3,5-Br)GAP, respectively (Figure 3B). After hydration, the scaffolds partially maintain the fibrillar and porous morphology and the peptide is still correctly integrated in the network (Figure 4).

[0086] Assessment of the antimicrobial activity of the scaffolds

[0087] The samples obtained were incubated in the True Tissue on a Platform culture system (TToP static module, TToP technology). Such a system consists of a static module for biological stability tests and is a two-compartment culture system, which allows the resilin / gelatin scaffolds to be mounted inside as porous membranes. With these modules the porous scaffold membranes were initially decontaminated with ethanol and mounted in the TToP static module (sterilized in ethanol), then the system was placed in 12 wells and filled with DMEM cell culture medium with 10% Fetal Calf Serum. For this test, multiwells containing the crosslinked matrix were prepared and immersed in culture medium and left in an incubator at controlled temperature (37°C), humidity (95%) and 5% CO2. The membranes were observed every 24 hours.

[0088] The scaffolds containing 30% (6C) and 70% (6B) by weight SDSY(3,5- Br)GAP (shown in Figure 1), respectively, never showed any type of contamination during the 14-day incubation period. In contrast, the samples consisting of gelatin alone (Figure 5A) and containing non- brominated SDSYGAP (Figure 5D) were affected by bacterial contamination in the first 24 hours of incubation. Therefore, the presence of bromine allows preventing bacterial contamination. Assessment of mechanical properties: strain-hardening behavior and resilience

[0089] The mechanical properties of the scaffolds were measured by tensile tests using an Anton Paar MGR 702 provided with linear drive (40 N load cell). Three to six replicates of a rectangular shape of 20 mm x 4 mm, with a thickness varying between 100 and 200 pm, were tested. Before each test, the samples were hydrated in MilliQ water for one hour to reach swelling equilibrium. During the test, the samples were subjected to an elongation of 2 mm / min until reaching breakage. Gradual cycle tensile tests were carried out at a beam speed of 2 mm / min at maximum incremental strains (15%. 30%. 45% and 60%) with hydrated samples. The recorded data were used to determine the recovery ratio (RR%) and resilience values (Res%), as follows: 00 wherein £ is the strain associated with zero stress in the unloading phase, Emax is the maximum strain achieved in each phase-strain cycle (15%, 30%, 45%, 60%) and Wunioad and Wioad are the areas under the stress-strain curves in the unloading and loading phases, respectively .

[0090] The tensile tests of the hydrated samples showed that the Res(Br)- based scaffolds showed a pronounced increase to progressive strain resistance, especially when the peptide concentration exceeded 70% w / w (RB7). In comparison, the scaffolds with the same wild-type sequence content (RW7) demonstrated a 60% reduction in strain at break, making them more fragile and prone to breakage (Table below and Figures 6 and 7b-7e). The non-linear mechanical behavior, combined with the tensile strength, elongation at break and Young's modulus values, highlights the suitability of these scaffolds for tissue engineering and soft material applications. Furthermore, the cyclic tests indicated greater energy storage and recovery capabilities in Res(Br)-based scaffolds, obtaining consistent recovery ratios greater than 70% and resilience values which exceeded both gelatin-only and wild-type peptide scaffolds (Figures 8f-8h). This behavior underlines the ability of the material to withstand and recover from mechanical stresses, a critical property for applications requiring dynamic mechanical performance, such as in tissue engineering and soft tissue scaffolds.

[0091] Table 1: Tensile strength, elongation at break, Young's modulus, recovery ratio and resilience values for electrospun scaffolds based on 100% gelatin, 70% SDSYGAP (RW7) and 70% SDSY (3,5Br)GAP (RB7).

[0092] Assessment of scaffold biodegradability: increased proteolytic stability of Res(Br)

[0093] To characterize the rate of scaffold degradation, an in vitro protease-induced degradation test was carried out. A solution of 0.01 U / mL protease XIV in PBS (pH 7.4) was prepared and used for incubating the scaffolds (3-4 mg) at 37°C, 98% RH. At appropriate time intervals, the scaffolds were washed with deionized water, allowed to dry and weighed, determining the final dry mass (md).

[0094] The results showed that the Res(Br) scaffolds significantly slowed degradation, losing only 41% of the mass thereof after 24 hours incubation in 0.01 U / mL protease XIV solution, with respect to the nearly complete dissolution of the wild-type and gelatin-only scaffolds in the same time frame. This increased proteolytic resistance, attributed to the presence of an unnatural amino acid, makes the material particularly suitable for environments which require stability against enzymatic degradation, such as tissue scaffolds and advanced wound healing matrices (Figure 9).

[0095] Assessment of antioxidant activity Antioxidant activity was assessed using ABTS and FRAP tests. For the

[0096] ABTS test, the radical stock solution was prepared by adding 2.45 mM ammonium persulfate to a 7 mM ABTS solution in MilliQ water and incubated for 16 hours in the dark at room temperature. The stock solution was progressively diluted with PBS to obtain a working solution with absorbance 0.61 at 734 nm. 1 mg of electrospun fibers was then added to 1 mL of radical solution, left to react for several time points and the absorbance was measured at 734 nm. The scavenged ABTS % was calculated as: wherein Ao is the absorbance of the starting radical solution and Af is the absorbance after addition of the scaffold.

[0097] For the FRAP test, a solution of 10 mM TPTZ (2.4.6-Tris(2-pyridyl)- s-triazine) in 40 mM HC1 and 20 mM aqueous FeCls•6H2O solution were prepared. The FRAP working solution was prepared by mixing the acetic acid buffer, TPTZ solution and FeCls solution according to the ratio (10:1:1) and incubated at 37°C. 1 mg of electrospun fibers was added to 1 mL of FRAP solution, left to react for several time points and the absorbance was measured at 593 nm. The FRAP value was calculated as mM equivalents of ascorbic acid (vitamin C) per mg of sample.

[0098] The Res(Br) -based scaffolds showed good ability to eliminate cationic radicals (ABTS assay (2,2' -Azino-bis(3- ethylbenzothiazoline-6-sulfonic acid)) and to reduce a complex based on ferric ion in the ferrous complex of intense blue color (FRAP assay). The Res(Br)-based scaffolds showed good antioxidant activity in both neutral (pH 7.4) and acidic (pH 3.6) environments, eliminating over 90% of ABTS radicals in 30 minutes and showing a reduction capacity four times greater with respect to the gelatin- only scaffolds (Figure 10).

[0099] These properties expand the functionality of the material beyond anti-biofouling, making it suitable for applications which require the mitigation of oxidative stress, such as in wound healing.

[0100] From the above description, the advantages offered by the present invention will be readily apparent to those skilled in the art.

[0101] The obtained materials exhibited high stability and resistance to microbial contamination under pathophysiological conditions, showing no signs of contamination even after 14 days of incubation.

[0102] Stability was also found from a mechanical point of view, as the prepared material proved to maintain the initial fibrillar and porous morphology .

[0103] The mechanical properties of the material are such as to allow all the applications described with excellent performance.

[0104] The materials used for the preparation of the scaffolds are biomolecules and the procedures for making them employ known and established technologies.

Claims

CLAIMS1. A process for preparing an antibacterial material, comprising the steps of:1) preparing a solution comprising a peptide of formula (I):SJXXZGXP wherein S is a serine residue, J is a serine residue or is absent, X is independently any desired amino acid, Z is an amino acid residue selected from: tyrosine, histidine, phenylalanine or tryptophan, G is a glycine residue and P is a proline residue, in which at least the Z residue is modified with at least one halogen selected from: Br, Cl, I; and2) electrospinning the solution obtained from step 1).

2. A process for preparing an antibacterial material according to claim 1, wherein said peptide has formula (I) wherein S is a serine residue, J is absent, X is independently any desired amino acid, Z is an amino acid residue selected from: tyrosine, histidine, phenylalanine or tryptophan, G is a glycine residue and P is a proline residue, wherein at least the Z residue is modified with at least one halogen selected from: Br, Cl, I.

3. A process for preparing an antibacterial material according to claim 1 or 2, wherein said peptide has formula (I) wherein S is a serine residue, J is absent, X is independently any desired amino acid, Z is a tyrosine residue, G is a glycine residue and P is a proline residue, wherein at least the Z residue is modified with at least one halogen selected from: Br, Cl, I.

4. A process for preparing an antibacterial material according to any one of claims 1 to 3, wherein said peptide has formula (I)wherein S is a serine residue, J is a serine residue or is absent, X is independently any desired amino acid, Z is a tyrosine residue, G is a glycine residue and P is a proline residue, wherein the phenolic group on said tyrosine residue Z is mono- or di-ortho- halogenated, preferably is di-ortho-brominated.

5. A process for preparing an antibacterial material according to any one of claims 1 to 4, wherein said peptide has formula (I) wherein S is a serine, J is absent, X is independently any desired amino acid, Z is a histidine, G is a glycine and P is a proline, wherein the imidazole on said histidine Z is mono- or di-halogenated, preferably is di-brominated.

6. A process for preparing an antibacterial material according to any one of claims 1 to 5, wherein said peptide has formula (I) wherein S is a serine residue, J is absent, X is independently any desired amino acid, Z is a phenylalanine residue, G is a glycine residue and P is a proline residue, wherein the phenyl on said phenylalanine residue Z is mono para-halogenated, wherein the halogen is preferably iodine.

7. A process for preparing an antibacterial material according to any one of claims 1 to 6, wherein said peptide has formula (I) wherein S is a serine residue, J is absent, X is independently any desired amino acid, Z is a tryptophan residue, G is a glycine residue and P is a proline residue, wherein the indole on said tryptophan residue Z is mono- or di-halogenated, preferably is di-brominated.

8. A process for preparing an antibacterial material according to any one of claims 1 to 7, wherein said peptide has formula:SDSY*GAPwherein S is a serine residue, D is an aspartic acid residue, Y* is a tyrosine residue, G is a glycine residue, A is an alanine residue and P is a proline residue, wherein Y* is a mono- or di-halogenated tyrosine residue, wherein said halogen is selected from chlorine, bromine and iodine.

9. A process for preparing an antibacterial material according to the preceding claim, wherein Y* is a di-brominated tyrosine residue.

10. A process for preparing an antibacterial material according to claim 8 or 9, wherein Y* is an ortho-brominated tyrosine residue and therefore said peptide has formula:SDSY(3,5 Br)GAP.

11. A process for preparing an antibacterial material according to any one of claims 1 to 10, wherein the solution of step 1) comprises a mixture of said peptide and another material or biomaterial.

12. A process for preparing an antibacterial material according to any one of claims 1 to 11, wherein said other material or biomaterial is selected from protein materials such as: gelatin, collagen, fibroin, sericin, elastin, keratin.

13. A process for preparing an antibacterial material according to any one of claims 1 to 12, wherein said peptide of formula SDS- Y(3,5 Br)-GAP is mixed with gelatin in a ratio between 1:9 and 9:1, wherein a ratio from 3:7 to 7:3 is particularly preferred.

14. A process for preparing an antibacterial material according to any one of claims 1 to 13, further comprising a step 3) of crosslinking the product obtained by electrospinning.

15. An antibacterial material obtained by the process according to any one of the preceding claims.

16. An antibacterial material according to the preceding claim which is in the form of fibers.

17. Fibers in the antibacterial material according to the preceding claim having a diameter of about 400-600 nm and preferably of 500-600 nm .

18. A biomedical device obtained with the antibacterial material according to claim 15 or 16 or with the fibers according to claim 17.

19. A device according to the preceding claim, wherein said device is selected from: prostheses, vascular stents, membranes, implantable devices; or parts or portions thereof.

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