Embedded-packaged kirschner wire composite functional coating with local anti-infection and percutaneous sealing performance and preparation method of embedded-packaged kirschner wire composite functional coating

Abstract

The invention discloses an embedded-packaged kirschner wire composite functional coating with local anti-infection and percutaneous sealing performance and a preparation method of the embedded-packaged kirschner wire composite functional coating. The method comprises the following specific steps: 1) determining an antibacterial coating embedding site on the kirschner wire as required; 2) forming two groove structures on the surface of the kirschner wire by using a fixed-point sanding technology based on the embedding site information; (3) after high-temperature vacuum cleaning, physical vapor deposition is conducted on an antibacterial coating with the thickness larger than the depth of the groove; 4) detecting the thickness of the coating except the groove by using a film thickness gauge, and machining and polishing the kirschner wire by taking the average thickness; and (5) finally, self-polymerizing a dopamine coating on the surface of the kirschner wire in situ and chemically grafting an epithelial repair promoting medicine on the surface of the kirschner wire, and cleaning and sterilizing to obtain the embedded-packaged kirschner wire composite functional coating with local anti-infection and percutaneous sealing properties. The coating ensures that when the kirschner wire is externally fixed and used, good anti-infection and percutaneous sealing effects are achieved at the wound skin position.

Description

Technical Field

[0001] The invention relates to a bone implant device preparation technology, and in particular to an embedded-encapsulated Kirschner wire composite functional coating having both local anti-infection and percutaneous sealing properties and a preparation method thereof. Background Art

[0002] External fixation is an extracorporeal pinning fixation method that punctures the bone with a steel needle and connects to a metal stent. It is mainly used to treat severe open fractures and soft tissue contusions, and its clinical usage rate is very high. Among them, Kirschner wires are an important component of external fixation. When used, the external fixation mainly uses Kirschner wires to contact the patient's bone tissue and skin tissue. However, due to the percutaneous characteristics, that is, part of the Kirschner wire will contact the external environment of the human body through the skin, resulting in the area where the Kirschner wire contacts the skin is very prone to infection, which seriously affects the patient's recovery.

[0003] At present, the commonly used clinical treatment method is to use alcohol, iodine and other disinfectants to disinfect the Kirschner wire needle channel, but this method is not effective and will cause physiological stimulation to the patient, bringing a huge psychological burden to the patient. The current solution to this problem is mainly to directly fight infection or promote the regeneration and repair of skin tissue to achieve the purpose of percutaneous sealing. Functional coating technology, with its convenience, practicality and efficiency, has attracted widespread attention in medical devices. If a new coating material with antibacterial and / or percutaneous sealing functions can be developed, it will greatly promote the solution of the above problems.

[0004] In view of the above problems, the present invention proposes an embedded-encapsulated Kirschner wire composite functional coating strategy with both local anti-infection and percutaneous sealing properties. It plans to start from both anti-infection and percutaneous sealing to promote the functional upgrade of traditional Kirschner wires and solve this clinical problem. Summary of the invention

[0005] The purpose of the present invention is to provide an embedded-encapsulated Kirschner wire composite functional coating with both local anti-infection and percutaneous sealing performance and a preparation method thereof to solve the problems of poor anti-infection and percutaneous sealing performance of Kirschner wires in external fixation stents. The coating of the present invention ensures that the Kirschner wire achieves good anti-infection and percutaneous sealing effects at the wound skin position when used for external fixation.

[0006] The present invention is implemented by the following technical solution, and the specific steps are as follows:

[0007] A method for preparing an embedded-encapsulated Kirschner wire composite functional coating having both local anti-infection and percutaneous sealing properties, comprising the following steps:

[0008] 1) Determine the locations of two antibacterial coating embedding sites on the surface of the Kirschner wire as needed;

[0009] 2) Based on the position information, two groove structures are opened on the surface of the Kirschner wire by using a grinding wheel combined with fixed-point sanding technology;

[0010] 3) After cleaning and drying the Kirschner wire, high-temperature vacuum cleaning is performed to remove the oxide layer on the surface of the Kirschner wire, and an antibacterial coating having a thickness greater than the depth of the groove is formed on the surface of the Kirschner wire in combination with physical vapor deposition (PVD);

[0011] 4) machining and polishing the Kirschner wire with the antibacterial coating on the surface, so that only the groove position is embedded with the antibacterial coating;

[0012] 5) In situ self-polymerization of dopamine coating and surface chemical grafting of epithelial repair promoting drugs are carried out on the polished surface of the Kirschner wire, and after cleaning and sterilization, an embedded-encapsulated Kirschner wire composite functional coating with both local anti-infection and percutaneous sealing properties is obtained.

[0013] Furthermore, in step 1), the spacing between the locations of the antibacterial coating embedding sites at the Kirschner wire 2 is equal to the length (span) of the Kirschner wire inserted into the skin, and the length of the Kirschner wire inserted into the skin is the outer diameter of the skin at the bone needle location.

[0014] Furthermore, in step 2), the depth of the groove structure is 5-30 μm and the width is 0.3-3 cm; the width of the grinding wheel is consistent with the width of the groove structure; and the rotation speed of the grinding wheel is 2000-4000 rpm when the groove is opened.

[0015] Furthermore, in step 3), during the high temperature vacuum cleaning process, the vacuum degree in the cleaning chamber is higher than 0.005 Pa, and then argon gas is introduced to maintain the vacuum degree at 2-5 Pa, the temperature in the chamber is maintained at 300-400° C., the voltage is 600-1000 V, the duty cycle is 50-70%, and the argon gas ionization cleaning is performed for 30-50 minutes;

[0016] During the PVD process, a silver target with a purity greater than 99.99% is used, the vacuum degree in the chamber is higher than 0.005Pa, the current is 15-25A, and the power density is 3-6W / cm 2 , temperature is 300-400℃, and deposition time is 15-60min.

[0017] Furthermore, in step 4), during the machining and polishing process, a film thickness meter is used to detect the coating thickness at at least 5 positions other than the groove and the average thickness is calculated. The Kirschner wire is machined according to the average thickness to achieve a consistent diameter at positions other than one end of the Kirschner wire. The end is a cone structure and polished using 100, 150 and 200 mesh grinding wheels in sequence to make the surface roughness of the Kirschner wire less than 0.8 microns.

[0018] Further, in step 5), during the preparation of the dopamine coating, dopamine hydrochloride is used as a raw material at a concentration of 8-12 mg / ml, the solvent system is a Tris-HCl buffer solution with a pH of 8.5, and the polymerization time is 4-12 h;

[0019] The surface chemically grafted epithelial repair promoting drug is one or more of eicosapentaenoic acid, curcumin, asiatica glycoside, lycium barbarum glycopeptide and rhubarb polysaccharide.

[0020] Furthermore, the antibacterial coating is a silver coating.

[0021] An embedded-encapsulated Kirschner wire composite functional coating having both local anti-infection and percutaneous sealing properties is obtained by using any of the above-mentioned preparation methods.

[0022] Compared with the prior art, the present invention has the following advantages:

[0023] 1) The present invention uses silver, dopamine hydrochloride, epithelial repair promoting drugs and the like as raw materials, and combines precision sand grinding, high temperature vacuum cleaning, PVD, surface self-polymerization, surface chemical grafting modification and other combined processes to prepare an embedded-encapsulated Kirschner wire composite functional coating material having both local anti-infection and percutaneous sealing properties. The above raw material selection and process combination are original to the present invention.

[0024] 2) The embedded-encapsulated Kirschner wire composite functional coating strategy with both local anti-infection and percutaneous sealing performance in the present invention is first created by the present invention in combination with the problem of needle tract infection of external fixators. In view of the high incidence of needle tract infection, the most direct conventional idea is to conduct anti-infection treatment, and currently basically only use drugs for repeated coating and disinfection, which is cumbersome to operate, has general effects, and causes obvious pain to patients. We also introduce the concept of antibacterial coating, and the antibacterial coating adopts the concept of local and embedded; and on this basis, further strengthen the percutaneous sealing, and further coordinate epithelial tissue repair technology on the primary treatment concept of treating infection, completely isolate the needle tract from the external air environment through skin regeneration, and achieve the dual purpose of inhibiting infection and completely cutting off the source of infection. It can more efficiently solve the clinical problem of needle tract infection of external fixators. This strategy shows great clinical practical value.

[0025] 3) The first-level embedded anti-infection silver coating structure + the second-level encapsulated percutaneous sealing coating structure in the present invention are designed according to actual clinical needs. In order to introduce two functions on the surface of the Kirschner wire at the same time, the present invention cleverly opens two groove structures on the Kirschner wire, and forms a first-level embedded anti-infection silver coating structure in the groove, and only sets the antibacterial coating in the two areas where the patient's skin contacts the Kirschner wire, which saves costs on the one hand and reduces the waste of raw materials on the other hand; because the anti-infection silver coating structure is embedded in the groove, the final silver coating is highly level with the surface of the Kirschner wire, so the feasibility of the Kirschner wire during insertion is guaranteed. In addition, a second-level encapsulated percutaneous sealing coating structure is further introduced on the flat surface of the Kirschner wire to achieve the wrapping of the surface of the Kirschner wire. When the Kirschner wire is implanted, it can play the function of promoting epithelial tissue repair on the entire contact surface, and achieve percutaneous sealing while inhibiting infection, so that the needle channel is fully isolated from the external environment, and the second level of protection is achieved.

[0026] 4) The new Kirschner wire product in the present invention has high biocompatibility, local anti-infection performance and percutaneous sealing performance at the same time. The above functions work together to overcome the problem of needle tract infection in the application of external fixation bracket materials. This product uses silver, dopamine hydrochloride, epithelial repair promoting drugs, etc. as raw materials, all of which have good biocompatibility, ensuring the subsequent application of the product. And by designing local anti-infection performance and full-thickness percutaneous sealing performance at the same time, it realizes the efficient prevention and treatment of needle tract infection problems when the external fixation bracket is used, and simultaneously promotes the healing of wound epithelial tissue, and realizes the blocking of the needle tract through skin repair, isolating the source of bacteria, and working together to solve this clinical problem.

[0027] 5) The present invention realizes new applications of traditional processes such as "sand grinding + PVD + machining + polishing + in-situ self-polymerization + surface chemical grafting modification". In the present invention, since it is necessary to ensure the effects of local antibacterial and comprehensive promotion of percutaneous sealing, and the diameter of each part of the surface of the Kirschner wire needs to be kept consistent, the combined process of sand grinding + PVD + machining + polishing is first used to introduce the required embedded anti-infection silver coating structure at the specified position, and the outer diameter of the Kirschner wire does not change after the introduction of the silver coating. Furthermore, in order to achieve the effect of percutaneous sealing, a universal primer is introduced through the in-situ self-polymerization reaction of dopamine (DA), and polydopamine (PDA) provides active reaction sites for subsequent surface chemical grafting of epithelial tissue repair drugs. The above two combined processes successfully achieve the introduction of a second-level uniform coating structure that promotes epithelial tissue repair on the surface of the Kirschner wire. So far, through the organic synergy between the above processes, the functional modification of the surface of the Kirschner wire has been successfully achieved. The selection and application of the above combined process matches the actual needs of the present invention and has obvious innovation.

[0028] 6) The embedded-encapsulated Kirschner wire composite functional coating strategy designed in the present invention with both local anti-infection and percutaneous sealing properties is universal. The required new Kirschner wire material can be customized by measuring the size of the patient's affected area. On the one hand, it can prevent and treat infection, and on the other hand, it can promote epithelial tissue repair and percutaneous sealing, which has great practicality and actual clinical significance. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 A schematic diagram of the preparation process of the composite functional coating for embedded-encapsulated Kirschner wires having both local anti-infection and percutaneous sealing properties according to the present invention;

[0030] Figure 2 This is an in vitro release curve of silver ions in an embedded-encapsulated Kirschner wire composite functional coating having both local anti-infection and percutaneous sealing properties according to an embodiment of the present invention (corresponding to Example 1). DETAILED DESCRIPTION

[0031] The technical solution of the present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments.

[0032] Comparative Example 1:

[0033] 1) First, measure the size of the patient's fracture site to determine the location of the two antibacterial coating embedding sites on the surface of the Kirschner wire. For example, if the patient's arm is 6 cm thick, determine that the interval between the antibacterial coating embedding sites on the surface of the Kirschner wire is 6 cm;

[0034] 2) Based on the above position information, a customized grinding wheel with a width of 2 cm (grinding wheel speed of 2000 rpm) was used in combination with fixed-point sanding technology to form two groove structures (depth of 5 μm and width of 2 cm) on the surface of the Kirschner wire;

[0035] 3) After the Kirschner wire was rinsed three times with deionized water and dried in a 60°C oven, it was further cleaned at high temperature and vacuum (first, the vacuum degree in the cleaning chamber was ensured to be higher than 0.005Pa, and then argon was introduced to maintain the vacuum degree at 5Pa, the chamber temperature was maintained at 300°C, the voltage was 600V, the duty cycle was 50%, and the argon ionization cleaning was performed for 30min) to remove the surface oxide layer, and combined with PVD (using a silver target with a purity greater than 99.99%, the vacuum degree in the chamber was higher than 0.005Pa, the current was 20A, and the power density was 5W / cm 2 , temperature 300°C, deposition time 15min) to form a silver coating with a thickness greater than the groove depth on the Kirschner surface;

[0036] 4) Use a film thickness meter to detect the coating thickness at at least 5 locations other than the groove and calculate the average thickness, and machine and polish the Kirschner wire according to the average thickness (during the polishing process, use 100, 150 and 200 mesh grinding wheels for polishing in turn, so that the surface roughness of the Kirschner wire is less than 0.8 microns) to achieve a consistent diameter of the Kirschner wire (except for the end, which is a cone), and ensure that only the groove position is embedded with silver coating, so as to obtain an embedded Kirschner wire composite functional coating with anti-infection properties.

[0037] In this comparative example, an embedded local silver coating structure with anti-infection function is provided. Combined with the CCK-8 detection kit, after 7 days of co-culture with endothelial cells, the cell survival rate is about 86%; when rats are used as experimental subjects, in the external fixation animal experiment, there is still some redness and swelling at the needle tract after 7 days, and the needle tract has not completely healed.

[0038] Comparative Example 2:

[0039] 1) In situ self-polymerization of a dopamine coating on the surface of a Kirschner wire (using dopamine hydrochloride as a raw material, a concentration of 8 mg / ml, a solvent system of a Tris-HCl buffer solution with a pH of 8.5, and a polymerization time of 8 h).

[0040] 2) Further chemically grafting eicosapentaenoic acid onto the surface of the Kirschner wire through an EDC coupling reaction, and after cleaning and sterilization, an encapsulated Kirschner wire composite functional coating with percutaneous sealing performance is obtained.

[0041] In this comparative example, a drug coating for promoting epithelial tissue regeneration is arranged on the surface of the Kirschner wire. Combined with the CCK-8 detection kit, after 7 days of co-culture with endothelial cells, the cell survival rate is about 93%; when rats are used as experimental subjects, in the external fixation animal experiment, obvious redness and swelling occurred at the needle tract after 7 days, and some exudation occurred.

[0042] Embodiment 1:

[0043] 1) First, measure the size of the fracture site of the patient to determine the location of the two antibacterial coatings, i.e., the silver coating, on the surface of the Kirschner wire. For example, if the patient's arm is 6 cm thick, determine that the interval between the antibacterial coatings on the surface of the Kirschner wire is 6 cm;

[0044] 2) Based on the above position information, a customized grinding wheel with a width of 2 cm (grinding wheel speed of 2000 rpm) was used in combination with fixed-point sanding technology to form two groove structures (depth of 5 μm and width of 2 cm) on the surface of the Kirschner wire;

[0045] 3) After the Kirschner wire was rinsed three times with deionized water and dried in a 60°C oven, it was further cleaned at high temperature and vacuum (first, the vacuum degree in the cleaning chamber was ensured to be higher than 0.005Pa, and then argon was introduced to maintain the vacuum degree at 5Pa, the chamber temperature was maintained at 300°C, the voltage was 600V, the duty cycle was 50%, and the argon ionization cleaning was performed for 30min) to remove the surface oxide layer, and combined with PVD (using a silver target with a purity greater than 99.99%, the vacuum degree in the chamber was higher than 0.005Pa, the current was 20A, and the power density was 5W / cm 2 , temperature 300°C, deposition time 15min) to form a silver coating with a thickness greater than the groove depth on the Kirschner surface;

[0046] 4) Use a film thickness meter to detect the coating thickness at at least 5 locations other than the groove and calculate the average thickness, and machine and polish the Kirschner wire according to the average thickness (in the polishing process, use 100, 150 and 200 mesh grinding wheels to polish the Kirschner wire surface roughness less than 0.8 microns) to achieve a consistent diameter of the Kirschner wire (except the end) and ensure that only the groove position is embedded with silver coating;

[0047] 5) Finally, a dopamine coating was in situ self-polymerized on the surface of the Kirschner wire (with dopamine hydrochloride as the raw material, the concentration was 8 mg / ml, the solvent system was a Tris-HCl buffer solution with a pH of 8.5, and the polymerization time was 8 h) and eicosapentaenoic acid was chemically grafted onto the surface through an EDC coupling reaction. After cleaning and sterilization, an embedded-encapsulated Kirschner wire composite functional coating with both local anti-infection and percutaneous sealing properties was obtained.

[0048] Compared with comparative example 1, this embodiment adds a drug coating that promotes epithelial repair on the basis of the local antibacterial coating. Combined with the CCK-8 detection kit, after 7 days of co-culture with endothelial cells, the cell survival rate is about 89%; when rats are used as experimental subjects for external fixation animal experiments, the needle tract heals well after 7 days, without redness, swelling, exudation and infection. Figure 2 This is the in vitro release curve of silver ions in the composite functional coating in this embodiment.

[0049] Embodiment 2:

[0050] 1) First, measure the size of the patient's fracture site to determine the location of the two antibacterial coating embedding sites on the surface of the Kirschner wire. For example, if the patient's arm is 6 cm thick, determine that the interval between the antibacterial coating embedding sites on the surface of the Kirschner wire is 6 cm;

[0051] 2) Based on the above position information, a customized grinding wheel with a width of 0.3 cm (grinding wheel speed of 2000 rpm) was used in combination with fixed-point sanding technology to form two groove structures (depth of 5 μm and width of 0.3 cm) on the surface of the Kirschner wire;

[0052] 3) After the Kirschner wire was rinsed three times with deionized water and dried in a 60°C oven, it was further cleaned at high temperature and vacuum (first, the vacuum degree in the cleaning chamber was ensured to be higher than 0.005Pa, and then argon was introduced to maintain the vacuum degree at 5Pa, the chamber temperature was maintained at 300°C, the voltage was 600V, the duty cycle was 50%, and the argon ionization cleaning was performed for 30min) to remove the surface oxide layer, and combined with PVD (using a silver target with a purity greater than 99.99%, the vacuum degree in the chamber was higher than 0.005Pa, the current was 20A, and the power density was 5W / cm 2 , temperature 300°C, deposition time 15min) to form a silver coating with a thickness greater than the groove depth on the Kirschner surface;

[0053] 4) Use a film thickness meter to detect the coating thickness at at least 5 locations other than the groove and calculate the average thickness, and machine and polish the Kirschner wire according to the average thickness (in the polishing process, use 100, 150 and 200 mesh grinding wheels to polish the Kirschner wire surface roughness less than 0.8 microns) to achieve a consistent diameter of the Kirschner wire (except the end) and ensure that only the groove position is embedded with silver coating;

[0054] 5) Finally, a dopamine coating was in situ self-polymerized on the surface of the Kirschner wire (with dopamine hydrochloride as the raw material, the concentration was 8 mg / ml, the solvent system was a Tris-HCl buffer solution with a pH of 8.5, and the polymerization time was 8 h) and eicosapentaenoic acid was chemically grafted onto the surface through an EDC coupling reaction. After cleaning and sterilization, an embedded-encapsulated Kirschner wire composite functional coating with both local anti-infection and percutaneous sealing properties was obtained.

[0055] Compared with Example 1, the width of the embedded silver coating in this embodiment is reduced to 0.3 cm. Combined with the CCK-8 detection kit, after 7 days of co-culture with endothelial cells, the cell survival rate is about 91%; when using rats as experimental subjects for external fixation animal experiments, due to the small width of the silver coating, the percutaneous area is difficult to completely match the local silver coating area. After 7 days, there is still some redness and swelling at the needle tract, and the needle tract is not completely healed.

Claims

1. A method for preparing an embedded-encapsulated Kirschner wire composite functional coating having both local anti-infection and percutaneous sealing properties, It is characterized in that The following steps are involved: 1) Determine the locations of two antibacterial coating embedding sites on the surface of the Kirschner wire according to specific needs; 2) Based on the position information, two groove structures are opened on the surface of the Kirschner wire by using a grinding wheel combined with fixed-point sanding technology; 3) After cleaning and drying the Kirschner wire, high-temperature vacuum cleaning is performed to remove the oxide layer on the surface of the Kirschner wire, and an antibacterial coating having a thickness greater than the depth of the groove is formed on the surface of the Kirschner wire in combination with physical vapor deposition (PVD); 4) machining and polishing the Kirschner wire with the antibacterial coating on the surface, so that only the groove position is embedded with the antibacterial coating; 5) In situ self-polymerization of dopamine coating and surface chemical grafting of epithelial repair promoting drugs are carried out on the polished surface of the Kirschner wire, and after cleaning and sterilization, an embedded-encapsulated Kirschner wire composite functional coating with both local anti-infection and percutaneous sealing properties is obtained.

2. The method for preparing the embedded-encapsulated Kirschner wire composite functional coating having both local anti-infection and percutaneous sealing properties according to claim 1, Features: In step 1), the spacing between the embedding sites of the antibacterial coating on the surface 2 of the Kirschner wire is equal to the length of the Kirschner wire inserted into the skin.

3. The method for preparing the embedded-encapsulated Kirschner wire composite functional coating having both local anti-infection and percutaneous sealing properties according to claim 1, Features: In step 2), the depth of the groove structure is 5-30 μm and the width is 0.3-3 cm; the width of the grinding wheel is consistent with the width of the groove structure; and the rotation speed of the grinding wheel is 2000-4000 rpm when the groove is opened.

4. The method for preparing the embedded-encapsulated Kirschner wire composite functional coating having both local anti-infection and percutaneous sealing properties according to claim 1, Features: Step 3) During the medium-high temperature vacuum cleaning process, the vacuum degree in the cleaning chamber is higher than 0.005Pa, and then argon gas is introduced to maintain the vacuum degree at 2-5Pa, the temperature in the chamber is maintained at 300-400°C, the voltage is 600-1000V, the duty cycle is 50-70%, and the argon gas ionization cleaning is performed for 30-50min; During the PVD process, a silver target with a purity greater than 99.99% is used, the vacuum degree in the chamber is higher than 0.005Pa, the current is 15-25A, and the power density is 3-6W / cm 2 , temperature is 300-400℃, and deposition time is 15-60min.

5. The method for preparing the embedded-encapsulated Kirschner wire composite functional coating having both local anti-infection and percutaneous sealing properties according to claim 1, Features: In step 4), during the machining and polishing process, a film thickness meter is used to detect the coating thickness at at least 5 positions other than the groove and the average thickness is calculated. The Kirschner wire is machined according to the average thickness to achieve a consistent diameter at positions other than one end of the Kirschner wire. Polishing is performed using 100, 150 and 200 mesh grinding wheels in sequence to make the surface roughness of the Kirschner wire less than 0.8 microns.

6. The method for preparing the embedded-encapsulated Kirschner wire composite functional coating having both local anti-infection and percutaneous sealing properties according to claim 1, Features: In step 5), during the preparation of the dopamine coating, dopamine hydrochloride is used as a raw material at a concentration of 8-12 mg / ml, the solvent system is a Tris-HCl buffer solution with a pH of 8.5, and the polymerization time is 4-12 h; The surface chemically grafted epithelial repair promoting drug is one or more of eicosapentaenoic acid, curcumin, asiatica glycoside, lycium barbarum glycopeptide and rhubarb polysaccharide.

7. The method for preparing the embedded-encapsulated Kirschner wire composite functional coating having both local anti-infection and percutaneous sealing properties according to claim 1, Features: The antibacterial coating is a silver coating.

8. An embedded-encapsulated Kirschner wire composite functional coating with both local anti-infection and percutaneous sealing properties, It is characterized in that The method is adopted as described in any one of claims 1 to 7.

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