TW201338817A - Biomedical implant material with composite antibacterium coating layer and manufacturing method thereof - Google Patents

Abstract

In a tri-electrode electrochemical system, a metallic biomedical implant that is electrically conductive is used as a working electrode and an acidic solution mixed with a biopolymer and antibiotic is used as an electrolyte of the tri-electrode electrochemical system. The temperature of the electrolyte is a fixed value between 25 DEG C and 75 DEG C. A constant potential is set with respect to a reference electrode of the tri-electrode electrochemical system. The constant potential is a fixed value between -0.5 and -3.0 volts. Electrochemical deposition is carried out accordingly to form a composite antibacterium coating layer of the biopolymer and the antibiotics on a surface of the biochemical implant material. The working electrode on which the deposition of the composite antibacterium coating layer has been completed is taken out to be air dried at 25 DEG C. The method of the present invention specifically increases medicine carrying amount per unit area for antibiotic and extends the release time of the antibiotic. Furthermore, a biomedical implant material manufactured with the present invention shows magnificent cell adhesion rate, proliferation, and differentiation.

Description

Biomedical implant material with composite antibacterial coating and manufacturing method thereof

The invention relates to electrochemically preparing a biopolymer/antibiotic composite antibacterial coating on a biomedical implant.

Any orthopedic related surgery has the potential to infect the bone with inflammation. The so-called osteomyelitis refers to a series of inflammatory reactions caused by microbial infection of bone tissue, thereby destroying the body of bone tissue. The type of pathogenic microorganisms are bacteria, fungi and mycobacteria, or even a virus; in which Staphylococcus aureus (staphylococcus aureus), intestinal bacteria (enterobacteriaceae), streptococci (streptococci) is the most common source of infection. If the patient has an orthopedic implant (such as a bone nail, a bone plate, an artificial joint, etc.) in the body, the strain is more likely to adhere or accumulate on the orthopedic implant, forming a problem of infection treatment. In order to solve this problem, a method of coating an antibiotic with an orthopedic implant has been proposed, in which the antibiotic and the orthopedic implant are implanted into the patient simultaneously to achieve the purpose of repairing the bone tissue and preventing infection.

Literature on antibiotic-coated orthopedic implants, such as:

Document 1: Volker Ait, Achim Bitschnau, Jana Osterling, Andreas Sewing, Christof Meyer, Ralf Kraus, Stefan A. Meissner, Sabine Wenisch, Eugen Domann, and Reinhard Schnettler, "The effects of combined gentamicin-hydroxyapatite coating for cementless joint prostheses on The reduction of infection rates in a rabbit infection prophylaxis model", Biomaterials, 27, 4627~4634 (2006).

Document 2: Peter J. Tarcha, Donald Verlee, Ho Wah Hui, Jeff Setesak, Bogdan Antone, Dellia Radulescu, and David Wallace, “The Application of Ink-Jet Techology for the Coating and Loading of Drug-Eluting Stents”, Annals of Biomedical Engineering, 35, 1793~1799 (2007).

Document 3: M. Stigter, K. de Groot, and P. Layrolle, "Incorporation of tobramycin into biomimetic hydroxyapatite coating on titanium", Biomaterials, 23, 4143-4153 (2002).

Document 4: Shula Radin, and Paul Ducheyne, "Controlled release of vancomycin from thin sol-gel films on titanium alloy fracture plate material", Biomaterials, 28, 1721 to 1729 (2007).

Document 5: Chen Yi'an, “Vancomycin/Calcium Phosphate Composite Coating on the Covered Biomedical Ceramic Ti6Al4V Implant Materials” Master's Thesis (Instructor: Yan Xiugang), Zhongxing University, 2008.

Document 6: Lin Biao, “Study on the Characteristics of Composite Coating of Calcium Phosphate, Gelatin and Jiandamycin on the Overlay of HA/TiO ₂ Titanium” (Instructor: Yan Xiugang), Zhongxing University, 2009.

Document 7: Luo Jun translated, "Study on the deposition of chitin/gelatin/vancomycin/calcium phosphate composite coating on titanium alloy" (Professor: Yan Xiugang), Zhongxingda, 2011.

In Literature 1 and Document 2, Gentamicin was sprayed on a stainless steel base coated with calcium phosphate (HA) or calcium phosphate-polypeptide complex (HA-RGD) by ink jet technology. On the material. The antibiotic drug loading is 200~250μg/cm ² , and the antibiotic release duration is 15~20 hours. This technique has two major drawbacks. If the geometry of the substrate is too complex, such as Vertebral Body Cages, it includes various geometric planes, rough surfaces, curvature surfaces, and various angles of intersection with the surface. The implementation of the technology has become difficult, it is not easy to spray evenly, and there is also the problem that it cannot be sprayed locally. In addition, the sprayed antibiotics only adhere to the surface of the substrate. Once the substrate is implanted into the human body, the antibiotics produce an initial burst, and the efficacy cannot be stably maintained for a period of time.

Document 3 uses a immersion method to co-precipitate a calcium phosphate salt and a tobramycin on a titanium alloy substrate. The disadvantage of this technique is that the processing time is long and it takes a day or more, while the antibiotic drug loading is only 5~10μg/cm ² and the antibiotic release duration is 50~60 hours.

In Document 4, vancomycin was plated on a titanium alloy substrate by a sol-gel method. The antibiotic drug loading is 35~50μg/cm ² , and the antibiotic release duration is 3~4 days. The disadvantage is that the manufacturing cost is high, and the substrate having an excessively complicated geometric shape has a problem of uneven plating and uneven distribution of drug concentration.

In Document 5, vancomycin and calcium phosphate composite coating (vancomycin-CaP) was further coated on Ti6Al4V alloy which has been coated with biomedical ceramics. The antibiotic drug loading was 26.6 μg/cm2 and the antibiotic release lasted approximately 24 hours.

Document 6, electrochemically plating gelatin, gentamicin and calcium phosphate on a two-layer coating of hydroxyapatite/titanium dioxide. The antibiotic drug loading was 46~94μg/cm2.

The object of the present invention is to provide a biomedical implant material having a composite antibacterial coating, wherein the biomedical implant is a conductive medical metal, and the surface of the biomedical implant has a biopolymer and an antibiotic composite antibacterial. The coating has a high unit area of antibiotic drug loading (up to 543 μg/cm ² ) and antibiotic release for up to 30 days. Moreover, due to the addition of biopolymers, cell attachment rate, cell proliferation and differentiation function are enhanced. Compared with the prior art literature, the antibiotic drug loading amount, stable release of antibiotics, duration of release, and recovery of tissue cells of the present invention are significantly improved.

The object of the present invention is to provide a method for preparing a biopolymer/antibiotic composite antibacterial coating on a biomedical implant material, which specifically increases the antibiotic drug loading per unit area and prolongs the release time of the antibiotic. In addition, the biomedical implants produced by the method of the present invention also have significant cell attachment rates, proliferation, and differentiation.

The object of the present invention is to provide a method for preparing a biopolymer/antibiotic composite antibacterial coating on a biomedical implant material, which is an electrochemical technique for co-precipitating a biopolymer and an antibiotic onto a conductive metal implant. The geometry of the biomedical implant does not limit the deposition of the electrochemical coating. The present invention can realize a comprehensive composite antibacterial coating on the biomedical implant plating on the biomedical implant of any geometric shape. .

The technology of the present invention to achieve the above object:

In a three-electrode electrochemical system, a conductive metal biomedical implant is used as a working electrode, and an acidic solution of a mixed biopolymer and an antibiotic is used as an electrolyte of the three-electrode electrochemical system, and the electrolyte temperature is a fixed value between 25 ° C and 75 ° C; a constant potential is set relative to a reference electrode of the three-electrode electrochemical system, the constant potential being a fixed value between -0.5 and -3.0 volts; Electrochemical deposition is performed to form a bio-polymer and antibiotic composite antibacterial coating on the surface of the biomedical implant; the working electrode for performing the composite antibacterial plating deposition is taken out and dried at 25 ° C.

The method for electrochemically depositing a biopolymer/antibiotic composite antibacterial coating on a biomedical implant is realized by a three-electrode electrochemical system. As shown in the first figure, the electrochemical system includes a reference electrode 20, an auxiliary electrode 30, a working electrode 50, a power supply unit 10 coupled to the upper electrodes, an operating unit 70 coupled to the power supply unit 70, and a container 40. In the electrolytic solution 60, each of the above electrodes is placed in the electrolytic solution 60. The electrolyte mainly contains antibiotics and biopolymers. The operating unit 70 includes a potentiostat Galvanostat and a computer 90, and the computer 90 is coupled to the potentiostat/current meter 80 to allow the operating unit 70 to pass the power unit 10 via the power unit 10. The reference electrode 20, the auxiliary electrode 30, and the working electrode 50 perform a conductive operation. The auxiliary electrode 30 is platinum. The reference electrode 20 is silver/silver chloride (Ag/AgCl), and the conductive potential is optimally set to a fixed value between -0.5 and -3.0 volts with respect to the reference electrode. The potentiostatic scan rate is approximately 0.167 mV/sec. The operating time is 600 sec. The working electrode 50 is an electrically conductive metal substrate for medical implantation having a diameter of 14 mm and a thickness of 1.0 mm. The operating temperature is a fixed value between 25 ° C and 75 ° C.

The electrochemical system is activated to form a biopolymer/antibiotic coating on the surface of the working electrode 50.

Thereafter, the working electrode was taken out from the electrolytic solution and dried in an environment of 25 ° C to complete the preparation.

Regarding the characteristics of the composite antibacterial coating, the present invention utilizes an X-ray diffractometer (XRD), a field emission scanning electron microscope (FESEM/EDS), a Fourier infrared spectroscopy (FTIR), and a transmission electron microscope (Transmission Electron Microscopy: TEM), respectively. ) for analysis.

Regarding the drug content of the composite antibacterial coating and drug release, the present invention is analyzed by a UV visible spectrometer.

Regarding the antibacterial test of the composite antibacterial coating, the present invention mainly measures the viable count of Staphylococcus aureus and analyzes it by the inhibition zone test.

Finally, cell culture, cell proliferation (MTT), alkaline phosphatase activity (ALP) and osteocalcin were used to detect the attachment, proliferation, differentiation and mineralization of osteoblasts on the test pieces.

<<Example 1: Electrochemical co-precipitation biopolymer chitosan and Jiandamycin in medical 316 stainless steel>>

In the first embodiment, the above electrochemical system was used. The electrolyte was mixed with 2 wt% chitosan and 10 mg/ml gentamicin dissolved in 0.0033 vol% acetic acid solution at a fixed voltage of -1.0 V and an operating temperature of 60 °C. The working electrode is a medically cleaned 316 stainless steel. Starting the above electrochemical system, chitosan and gentamicin produce a cathodic deposition reaction on the working electrode to form a chitosan/gentamicin composite antibacterial coating. After the cathode deposition reaction is completed, the working electrode is taken out from the electrolyte, and the preparation is completed after drying at 25 ° C.

The second figure is a polarization curve of the composite coating of chitosan and gentamicin in the first embodiment, and a reaction curve 120 and a reaction zone 130 of chitosan and gentamicin composite plating are seen.

The electrochemical reactions that may occur are as follows:

4H ⁺ +O ₂ +4e ^- →2H ₂ O E ₀ =0.5~-0.25V vs. Ag/AgCl

2H ⁺ +2e ^- →H ₂ E ₀ =-0.25~-0.75V vs. Ag/AgCl

2H ₂ O+2e ^- →H ₂ +2OH ^- E ₀ =-0.75~-3.0V vs. Ag/AgCl

Chitosan-NH ₃ ⁺ ₍₁₎ +OH ^- →Chitosan-NH _2(↓) +H ₂ O

It can be seen from the above electrochemical reaction that during the deposition of chitosan, the gentamicin contains an amino bond which can be combined with chitosan to coprecipitate on the medical stainless steel, thereby obtaining the optimal condition of chitosan and The electromycin microscopic observation of the gentamicin composite antibacterial coating is as shown in the sixth figure. The antibacterial coating has a thickness of about 3.6 μm, the gentamicin has a drug loading of 204.16 μg/cm ² , the inhibition zone diameter d (mm) is 32, and the pharmacodynamic release time can be maintained for 28 days; Osteoblasts can indeed attach, proliferate, differentiate, and mineralize.

<<Example 2: Electrochemical co-precipitation of chitosan and vancomycin in medical CCM alloy (cobalt-chromium-molybdenum alloy, Co-Cr-Mo alloy)>>

In the second embodiment, the above electrochemical system is used. The electrolyte is mixed with 2 wt% chitosan and 10 mg/ml vancomycin dissolved in 0.0033 vol% acetic acid solution, the fixed voltage is -1.0 V, and the operating temperature is 60 °C. The working electrode is a medically cleaned CCM alloy. Starting the above electrochemical system, chitosan and vancomycin produce a cathodic deposition reaction on the working electrode to form a chitosan/vancomycin composite antibacterial coating. After the cathode deposition reaction is completed, the working electrode is taken out from the electrolyte, and the preparation is completed after drying at 25 ° C.

The third figure is the polarization curve of the composite coating of chitosan and vancomycin in the second embodiment, and a reaction curve 140 and a reaction zone 150 of chitosan and vancomycin composite plating are seen. The electrochemical reactions that may occur are as follows:

4H ⁺ +O ₂ +4e ^- →2H ₂ O E ₀ =0.5~-0.2V vs. Ag/AgCl

2H ⁺ +2e ^- →H ₂ E ₀ =-0.2~-0.9V vs. Ag/AgCl

2H ₂ O+2e ^- →H ₂ +2OH ^- E ₀ =-0.9~-3.0V vs. Ag/AgCl

Chitosan-NH ₃ ⁺ ₍₁₎ +OH ^- →Chitosan-NH _2(↓) +H ₂ O

It can be seen from the above electrochemical reaction that in the process of depositing chitosan, vancomycin contains an amino bond and can be combined with chitosan to coprecipitate on the CCM alloy for medical use, thereby obtaining optimal conditions of chitosan/ The vancomycin composite antibacterial coating has an electron microscope observation chart as shown in the seventh figure. The antibacterial coating has a thickness of about 3.6 μm, the gentamicin has a drug loading of 543.42 μg/cm ² , and the inhibition zone diameter d (mm) is 32. The release time of the drug can be maintained for 30 days; in the cell culture experiment, the bone cells can be attached, proliferated, differentiated, and mineralized.

<<Example 3: Electrochemical co-precipitating gelatin, calcium phosphate salt and Jiandamycin in medical titanium metal>>

The third embodiment adopts the above electrochemical system, the electrolyte is mixed calcium phosphate salt (0.042M Ca(NO ₃ ) ₂ ‧4H ₂ O and 0.025M NH ₄ H ₂ PO ₄ ), 0.3wt% gelatin and 10 mg/ml The adriamycin is in acetic acid solution, the fixed voltage is -1.0V, and the operating temperature is 60 °C. The working electrode is a medically-used titanium metal that has been ground and cleaned. Starting the above electrochemical system, gelatin, calcium phosphate and Jiandamycin produce a cathodic deposition reaction on the working electrode to form a gelatin/calcium phosphate/gentamicin composite antibacterial coating. After the cathode deposition reaction is completed, the working electrode is taken out from the electrolyte, and the preparation is completed after drying at 25 ° C.

The fourth figure is a polarization curve of the composite coating of gelatin, calcium phosphate and gentamicin in the third embodiment. A reaction curve 100 and a reaction zone 110 of a composite coating of calcium phosphate and gelatin and gentamicin are visible. The electrochemical reactions that may occur are as follows:

O ₂ +2H ₂ O+4e ^- →4OH ^- E ₀ =0~-0.5V vs. Ag/AgCl

2H ⁺ +2e ^- →H ₂ E ₀ =-0.5~-1.0V vs. Ag/AgCl

2H ₂ PO ^4- +2e ^- →2HPO ₄ ^2- +H ₂ E ₀ =-1.0~-1.6V vs. Ag/AgCl

H ₂ PO ₄ ^- +2e ^- →PO ₄ ^3- +H ₂

2H ₂ O+2e ^- →H ₂ +2OH ^- E ₀ =-1.6~-3.0V vs. Ag/AgCl

After the following chemical reactions:

Ca ²⁺ +HPO ₄ ^2- +2H ₂ O→CaHPO ₄ ‧2H ₂ O(DCPD)

8Ca ²⁺ +8HPO ₄ ^2- +5H ₂ O→Ca ₈ H ₂ (PO ₄ ) ₆ ‧5H ₂ O+2H ₃ PO ₄ (OCP)

8Ca ²⁺ +2HPO ₄ ^2- +4PO ₄ ^3- +5H ₂ O→Ca ₈ H ₂ (PO ₄ ) ₆ ‧5H ₂ O(OCP)

10Ca ²⁺ +6PO ₄ ^3- +2OH ^- →Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ (HA)

It can be seen from the above electrochemical reaction that in the process of depositing calcium phosphate phosphate such as DCPD, OCP, HA, etc., because of the ammonia bond between the aqueous solution of gentamicin, gelatin, and Ca ²⁺ and H ₂ PO ^4- The gelatin/oxygen machine apatite/gentamicin composite coating is formed by forming the wrong ions in the titanium metal for medical treatment. The antibacterial coating has a drug-loading amount of 106.34 μg/cm ² , a diameter of d (mm) of 35, and a release time of 28 days; in cell culture experiments, bone cells can be attached. , proliferation, differentiation, and mineralization.

<<Example 4: Electrochemical co-precipitation of calcium phosphate and collagen, vancomycin in medical nickel-titanium alloy (Ni-Ti)>>

Embodiment 4 uses the above electrochemical system, the electrolyte is mixed calcium phosphate salt (0.042M Ca(NO ₃ ) ₂ ‧4H ₂ O and 0.025M NH ₄ H ₂ PO ₄ ), 0.025% collagen and 10 mg/ml Wangu The solution was in aqueous solution at an operating temperature of 60 °C. The working electrode is a medical nickel-titanium alloy that has been ground and cleaned. Starting the above electrochemical system, collagen, calcium phosphate and vancomycin produce a cathodic deposition reaction on the working electrode to form a collagen/calcium phosphate/vancomycin composite antibacterial coating. After the cathode deposition reaction is completed, the working electrode is taken out from the electrolyte, and the preparation is completed after drying at 25 ° C.

The fifth figure is a polarization curve of the composite coating of collagen, calcium phosphate and vancomycin in the fourth embodiment. A reaction curve 160 and a reaction zone 170 of a composite coating of calcium phosphate with collagen and vancomycin are visible. The electrochemical reactions that may occur are as follows:

O ₂ +2H ₂ O+4e-→4OH ^- E ₀ =0~-0.5V vs. Ag/AgCl

2H ⁺ +2e-→H ₂ E ₀ =-0.5~-1.0V vs. Ag/AgCl

2H ₂ PO ^4- +2e ^- →2HPO ₄ ^2- +H ₂ E ₀ =-1.0~-1.6V vs. Ag/AgCl

H ₂ PO ₄ ^- + ₂ ^- →PO ₄ ^3- +H ₂

2H ₂ O+2e ^- →H ₂ +2OH ^- E ₀ =-1.6~-3.0V vs. Ag/AgCl

After the following chemical reactions:

Ca ²⁺ +HPO ₄ ^2- +2H ₂ O→CaHPO ₄ ‧2H ₂ O(DCPD)

8Ca ²⁺ +8HPO ₄ ^2- +5H ₂ O→Ca ₈ H ₂ (PO ₄ ) ₆ ‧5H ₂ O+2H ₃ PO ₄ (OCP)

8Ca ²⁺ +2HPO ₄ ^2- +4PO ₄ ^3- +5H ₂ O→Ca ₈ H ₂ (PO ₄ ) ₆ ‧5H ₂ O(OCP)

10Ca ²⁺ +6PO ₄ ^3- +2OH ^- →Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ (HA)

It can be seen from the above electrochemical reaction that in the process of depositing calcium phosphate phosphate such as DCPD, OCP, HA, etc., because of the ammonia bond between aqueous solution, vancomycin, collagen, and Ca ²⁺ and H ₂ PO ^4- The effect is to form a counter electrode to co-precipitate on the conductive substrate, thereby obtaining an optimum condition of the oxyhydrogen machine apatite/collagen/vancomycin composite coating. The antibacterial coating had a statin-loading amount of 174.5 μg/cm ² and a zone diameter d (mm) of 35. The release time of the drug was maintained for 28 days; in the cell culture experiment, the bone cells were indeed attached, proliferated, differentiated, and mineralized.

<<Conclusion>>

The invention deposits biopolymers and antibiotics on medical metal implants by electrochemical techniques. It is known that antibiotics cannot be deposited by electrochemical means alone, but can form a biopolymer/antibiotic complex by forming a hydrogen bond with a biopolymer and deprotonating the biopolymer in an electrochemical process. Plating.

The results of XRD, TEM, FESEM, FTIR and UV/Vis analysis show that the biodeposited biopolymer film is composed of nanofibers. When the antibiotics are added, the diameter of the biopolymer fibers is reduced due to the decrease of pH. Molecules are intercalated between biopolymer fibers. Obviously, antibiotics can easily bond with biopolymers and sink in medical metal.

In biopolymer/antibiotic composite coatings, the drug loading of antibiotics can be controlled by deposition time and potential. The applied voltage range of the present invention is -0.5 to -3.0 volts. When the applied voltage is increased, the drug loading of the antibiotic is also increased, ranging from 150 to 550 μg/cm ² .

The antibacterial test results showed that the number of colonies was not found on the test piece containing the biopolymer/antibiotic composite coating, that is to say, the vancomycin was not deteriorated and the sterilization ability was lost during the electrochemical deposition process.

The antibiotic release test showed that the initial burst was 55%, followed by a 20% steady release from day 1 to day 5, and the last remaining 25% was from 6 days to a month later. At a slower release, the inhibition zone formed in the antibacterial test with a diameter of 30 mm to 35 mm was maintained for more than one month.

Cell culture tests have shown that the deposition of biopolymer/antibiotic composite coating on medical titanium alloy implants can effectively enhance the proliferation, differentiation and mineralization of osteoblasts. This result shows that biopolymers complement the antibiotics. Negative effects on bone cells.

Chitosan is a biopolymer and is the most abundant natural polysaccharide on earth. Because of its biocompatibility, biodegradability, hydrophilicity, non-toxicity and antibacterial properties, it has been widely used in biomedical engineering. Vancomycin and gentamicin are broad-spectrum antibiotics with good therapeutic and preventive effects against Gram-positive bacteria. Based on the advantages of chitosan and vancomycin, and gentamicin, they have been used in combination in the treatment of osteomyelitis. Although the experiment of the present invention is mainly based on chitosan, gelatin, vancomycin and gentamicin, those skilled in the art can derive different forms of changes according to the disclosure provided by the specification of the present invention. Includes the selection of biopolymers and antibiotics, or a mixture of two or more antibiotics. Therefore, the embodiments of the present invention are only used to illustrate the present invention and are not intended to limit the scope of the present invention. All kinds of modifications or changes that are not in violation of the spirit of the case are the scope of patent application in this case.

The working electrodes used in the present invention are medical metals having good biocompatibility and mechanical properties, and these medical metals have been widely used in surgery, particularly in the field of orthopedics. The above experimental results of the present invention show that the addition of biopolymer can enhance cell attachment, proliferation and differentiation, and it enables orthopedic implants to exhibit good osseointegration ability; and the addition of biopolymer also significantly increases antibiotic drug loading. In addition, the medical implants can exhibit better antibacterial effects; in addition, the addition of biopolymers can provide a slower release of antibiotics, thus prolonging the duration of antibiotic action and expecting the implanted The body maintains an average concentration of antibiotics.

20. . . Reference electrode

30. . . Auxiliary electrode

40. . . container

50. . . Working electrode

60. . . Electrolyte

70. . . Operating unit

80. . . Potentiostat/current meter

90. . . computer

The first figure is a schematic diagram of the configuration of the three-pole electrochemical system of the present invention.

The second figure is a polarization curve of a composite coating of chitosan and gentamicin according to an embodiment of the present invention.

The third figure is a polarization curve of the composite coating of chitosan and vancomycin according to the second embodiment of the present invention.

The fourth figure is a polarization curve of a composite coating of calcium triphosphate salt and gelatin and gentamicin according to an embodiment of the present invention.

The fifth figure is a polarization curve of the composite coating of the calcium phosphate salt, collagen and vancomycin of the present invention.

The sixth figure is a scanning electron microscope observation view of the composite coating of chitosan and gentamicin of the present invention.

The seventh figure is a scanning electron microscope observation view of the composite coating of chitosan and vancomycin of the present invention.

Claims (13)

A biomedical implant material with a composite antibacterial coating, comprising: a biomedical implant material, which is a conductive medical metal; and a composite antibacterial coating layer electroplated on the surface of the biomedical implant material, the composite The antibacterial coating is a mixture of biopolymer and antibiotic. The biomedical implant material having a composite antibacterial coating according to the first aspect of the patent application, wherein the biopolymer is an alternative of gelatin, chitosan and collagen. The biomedical implant material having a composite antibacterial coating according to claim 1, wherein the antibiotic is a single antibiotic or a mixture of two or more antibiotics. The biomedical implant material having a composite antibacterial coating according to claim 3, wherein the antibiotic is vancomycin and Gentamicin. The biomedical implant material having a composite antibacterial coating according to claim 1, wherein the composite antibacterial coating further comprises a calcium phosphate salt. The biomedical implant material having a composite antibacterial coating according to claim 5, wherein the calcium phosphate salt comprises calcium hydrogen phosphate (DCPD), octacalcium phosphate (OCP), and hydroxyapatite (HA). A method for manufacturing a biomedical implant material with a composite antibacterial coating, comprising: in a three-electrode electrochemical system, using a conductive metal biomedical implant as a working electrode to mix an acidic solution of a biopolymer and an antibiotic As the electrolyte of the three-electrode electrochemical system, the electrolyte temperature is a fixed value between 25 ° C and 75 ° C; a constant potential is set relative to the reference electrode of the three-electrode electrochemical system, and the constant potential is a fixed value between -0.5 and -3.0 volts; according to the electrochemical deposition, a biopolymer and antibiotic composite antibacterial coating is formed on the surface of the biomedical implant; the working electrode for the composite antibacterial deposition is completed Remove and dry at 25 ° C. The manufacturing method according to claim 7, wherein the electrolyte is an acidic solution in which 2 wt% of chitosan and 10 mg/ml of gentamicin are mixed. The manufacturing method according to claim 7, wherein the electrolyte is an acidic solution in which 2 wt% of chitosan and 10 mg/ml of vancomycin are mixed. The manufacturing method according to claim 7, wherein the electrolyte is a solution of a mixed biopolymer, an antibiotic, and a calcium phosphate salt. The manufacturing method according to claim 10, wherein the electrolyte is mixed with 0.042 M calcium nitrate [Ca(NO ₃ ) ₂ ‧4H ₂ O], 0.025 M ammonium dihydrogen phosphate [NH ₄ H ₂ PO ₄ ], 0.025 wt % A solution of collagen and 10 mg/ml vancomycin. The manufacturing method according to claim 10, wherein the calcium phosphate salt is an alternative to calcium hydrogen phosphate (DCPD), octacalcium phosphate (OCP), and hydroxyapatite (HA). The manufacturing method according to claim 7, wherein the conductive metal biomedical implant is selected from the group consisting of medical stainless steel, cobalt-chromium-molybdenum alloy, titanium, and nickel titanium.