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US-12616576-B2 - Methods of modifying the porous surface of implants

US12616576B2US 12616576 B2US12616576 B2US 12616576B2US-12616576-B2

Abstract

Methods are provided for modifying a porous surface of an implantable medical device by subjecting the porous surface to a modified micro-arc oxidation process to improve the ability of the medical device to resist microbial growth, to improve the ability of the medical device to adsorb a bioactive agent or a therapeutic agent, and to improve tissue in-growth and tissue on-growth of the implantable medical device.

Inventors

  • Devendra Gorhe
  • Donald L. Yakimicki
  • Philip McBride

Assignees

  • BIOMET MANUFACTURING, LLC

Dates

Publication Date
20260505
Application Date
20220629

Claims (20)

  1. 1 . A method of manufacturing a medical device, comprising: securing an electrode to a metallic substrate in an electrolyte solution, wherein the metallic substrate includes a porous layer and a non-porous layer, wherein the porous layer is configured to facilitate tissue in-growth or tissue on-growth; providing a cathode in the electrolyte solution; applying a voltage to the metallic substrate to form a plurality of micro-pores on the porous layer by micro-arc oxidation; and simultaneously depositing a therapeutic agent on the non-porous layer and on the porous layer of the metallic substrate in the plurality of micro-pores; wherein depositing the therapeutic agent comprises electrophoretic deposition or electrodeposition of the therapeutic agent.
  2. 2 . The method of claim 1 , wherein applying the voltage includes using a controller to control the voltage and timing of application of the voltage to the metallic substrate, wherein the controller comprises a switch, a circuit board, a relay, or a combination thereof.
  3. 3 . The method of claim 1 , further comprising circulating the electrolyte solution through a temperature regulating device to maintain a temperature of the electrolyte solution within a desired range while applying the voltage.
  4. 4 . The method of claim 1 , wherein the porous layer comprises an anode of an electrolytic cell and the cathode of the electrolytic cell is in the electrolyte solution.
  5. 5 . The method of claim 1 , wherein depositing the therapeutic agent on the porous layer having the plurality of micro-pores includes switching the voltage to the cathode on and off at least twice, and wherein depositing the therapeutic agent comprises electrophoretic deposition or electrodeposition of the therapeutic agent in a second electrolyte solution.
  6. 6 . A method of manufacturing a medical device, comprising: securing an electrode to a metallic substrate in an electrolyte solution, wherein the metallic substrate includes a porous layer and a non-porous layer, wherein the porous layer is configured to facilitate tissue in-growth or tissue on-growth; providing a cathode in the electrolyte solution; applying a voltage to the metallic substrate to form a plurality of micro-pores on the porous layer by micro-arc oxidation; and depositing a therapeutic agent on the non-porous layer and on the porous layer of the metallic substrate in the plurality of micro-pores; wherein depositing the therapeutic agent comprises electrophoretic deposition or electrodeposition of the therapeutic agent and wherein depositing the therapeutic agent includes performing a second depositing process to deposit the therapeutic agent on the non-porous layer.
  7. 7 . The method of claim 6 , further comprising applying a first voltage to the porous layer and applying a second voltage to the non-porous layer, wherein the first voltage is different from the second voltage.
  8. 8 . The method of claim 1 , wherein the plurality of micro-pores are treated by acid etching.
  9. 9 . A method of manufacturing a medical device, comprising: securing an electrode to a metallic substrate in an electrolyte solution, wherein the metallic substrate includes a porous layer and a non-porous layer; providing a cathode in the electrolyte solution; and applying a voltage to the metallic substrate to form a plurality of micro-pores on a porous layer of the metallic substrate by micro-arc oxidation, wherein the porous layer is configured to facilitate tissue in-growth or tissue on-growth; circulating the electrolyte solution through a temperature regulating device to maintain a temperature of the electrolyte solution within a desired temperature range while applying the voltage; depositing a therapeutic agent on the plurality of micro-pores on the metallic substrate; and manipulating the voltage to the cathode or manipulating a current to control depositing of the therapeutic agent; wherein manipulating the voltage to the cathode or manipulating the current to control depositing of the therapeutic agent includes controlling the depositing to achieve a desired amount or concentration of the therapeutic agent absorbed by the porous layer and by the non-porous layer.
  10. 10 . The method of claim 9 , wherein the voltage during the micro-arc oxidation has a root mean square of 200V.
  11. 11 . The method of claim 9 , wherein manipulating the voltage includes switching the cathode on and off at least twice.
  12. 12 . The method of claim 1 , wherein the electrolyte solution is maintained at temperature of 0° C. to 50° C.
  13. 13 . The method of claim 1 , wherein the therapeutic agent includes iodine compounds having a concentration of between 1% to about 10%, by weight or by volume.
  14. 14 . The method of claim 1 , further comprising applying heat to dry the medical device.
  15. 15 . The method of claim 1 , further comprising applying a voltage to the non-porous layer in a sequence with applying the voltage to the metallic substrate to form the plurality of micro-pores in the porous layer by micro-arc oxidation.
  16. 16 . The method of claim 1 , further comprising applying a voltage to the non-porous layer received in the electrolyte solution with the porous layer.
  17. 17 . The method of claim 1 , wherein depositing the therapeutic agent on the non-porous layer and on the porous layer of the metallic substrate in the plurality of micro-pores includes controlling the depositing to achieve a desired amount or concentration of the therapeutic agent absorbed by the porous layer and by the non-porous layer.
  18. 18 . The method of claim 9 , wherein manipulating the voltage to the cathode or manipulating the current includes applying an alternating current as a rectified sine wave.
  19. 19 . The method of claim 9 , wherein maintaining the temperature of the electrolytic solution includes continuously withdrawing the electrolyte solution from a container through at least a first pipe and continuously adding the electrolyte solution that has been cooled to the desired temperature range through at least a second pipe to the container.
  20. 20 . The method of claim 9 , further comprising applying a voltage to the non-porous layer received in the electrolyte solution with the porous layer.

Description

CLAIM OF PRIORITY This application is a continuation of U.S. application Ser. No. 17/151,352, filed Jan. 18, 2021, which is a continuation of U.S. application Ser. No. 15/940,382, filed Mar. 29, 2018, now issued as U.S. Pat. No. 10,893,944, which claims the benefit of U.S. Provisional Patent Application Ser. No. 62/478,821, filed on Mar. 30, 2017, the benefit of priority of each of which is claimed hereby, and each of which is incorporated by reference herein in its entirety. FIELD The present disclosure relates to medical devices, and particularly to implantable medical devices having modified porous surfaces, and methods of modifying the porous surfaces of implantable medical devices using modified micro-arc oxidation processing. BACKGROUND This section provides background information related to the present disclosure, which is not necessarily prior art. Implantable medical devices (also referred to herein as a medical implant or implant) are routinely used in orthopedic, trauma and other surgeries, e.g. prosthetic implants (implants for orthopedic, dental/orthodontal, maxillofacial, trauma, or plastic surgery), nails, screws, pins, wires, plates, external and internal fixators, valves, artificial blood vessels, shunts, stents, catheters and other endoprostheses. Examples of biocompatible materials used in implantable medical devices include polymers, ceramics, aluminum, vanadium, tantalum, iron, titanium, titanium alloys (e.g., Ti6Al4V, Ti6Al7Nb), stainless steels, alloys of nickel, niobium, cobalt, molybdenum, and chromium, Co—Cr alloys, magnesium, and other metals and metal alloys. However, medical implants formed of metals or metal alloys cannot be chemically bonded to tissue, resulting in the formation of gaps and loosening of the implant over the time of use. A medical implant formed of metals or metal alloys can be processed to create surface modifications to improve fixation of the implant in tissue. Medical implants can be modified to have roughened or porous coatings or surfaces (roughened coatings and surfaces may also be referred to herein, collectively, as “porous surfaces”), and such modified implants are particularly useful for medical interventions where tissue in-growth or tissue on-growth is desired to fix the implant within the body. However, roughened or porous coatings and surfaces can create additional surface area for bacterial adherence and growth on the medical implant. Implant-related infections remain a leading cause for treatment failure and are associated with significant economic and social costs. Biofilm formation, a critical event in the development of implant-related infection, begins immediately after bacterial adhesion on an implant and effectively protects the adhered microorganisms from the host immune response and from antibiotics and other antimicrobial pharmaceutical interventions. Efforts to reduce implant-related infection have focused on the ability of implant surface modifications to minimize bacterial adhesion, inhibit biofilm formation, and/or provide effective bacterial killing to protect implanted medical devices. Medical implants are known to have anodized surfaces for advantageously receiving a deposit of antimicrobial agents, such as metallic elements and metallic ions, and anti-microbial compositions containing metallic elements or metallic ions, e.g., copper and silver. Such devices and methods of forming such devices are disclosed, for example, in: U.S. Pat. Nos. 7,695,522; 8,858,775; 8,888,983; 8,945,363; 9,080,250; 9,096,943; and 9,393,349; U.S. Patent Pub. No. 2013/0319869; U.S. Patent Pub. No. 2015/0110844; and U.S. Patent Pub. No. 2015/0299865. Medical implants are also known to have anodized surfaces for deposition of other antimicrobial agents, e.g. iodine and compositions comprising iodine, e.g., U.S. Patent Pub. No. 2011/0313539, which is suitable for medical implants having smooth surfaces that do not facilitate tissue in-growth or tissue on-growth. However, these methods do not provide the desired surface modification on a medical implant having a porous surface or porous coating. Because of their extensive surface area, porous medical implant surfaces and porous coatings on implant surfaces draw large electrical currents when the implant is subjected to standard anodization. These large electrical currents generate heat and prevent or diminish oxidation of the porous surface or porous coating. The potential crevices in porous surfaces of medical implants may result in active dissolution of the anode, which also prevents oxide formation. Such problems can be avoided by masking the roughened or porous surface or coating on the implant to diminish the large draw of current by such surfaces. However, the masked portions of the implant will not become anodized and will, therefore, not advantageously adsorb the antimicrobial or other therapeutic agent. Micro-arc oxidation (also known as plasma electrolytic oxidation, spark anodization deposition,