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  6. J1-9169

J1-9169

Multifunctional bioactive coatings on different substrates for biomedical applications

Project Group

Project leader: assoc. prof. Matjaž Finšgar

Participating research organizations:

  1. University of Maribor, Faculty of chemistry and chemical engineering
  2. University of Maribor, Faculty of Medicine
  3. University ob Maribor, Faculty of mechanical engineering
  4. University of Nova Gorica

https://cris.cobiss.net/ecris/si/en/project/17271

Project Description

The aim of this project is to develop novel bioactive coatings from various combinations of naturally occurring polysaccharides and/or synthetic polymers on medical stainless steel and TiAlV alloys with enhanced durability and corrosion resistance properties. Such coatings would be superior to the most advanced products currently available on the market.

Our approach enables the design of coatings with adjustable hydrophilicity and antimicrobial and anti-inflammatory activities. These properties stimulate the ability of the implant to bind to the surrounding bone, thus allowing the incorporation of the graft into the host site (osteointegration). A detailed understanding of the interactions between the metal, polymer, therapeutic agents, cells, and biological environment is the driving force for coating optimization. These interactions are often overlooked, yet extensive study thereof is the only way to understand the behaviour of any artificial material exposed to such harsh and complex environment as the human body. The design and simulation of the targeted application and systematic evaluation of the performance of the materials in an in vitro simulated environment is therefore an integral part of the development of novel biomedical materials in this project.

The intricate interactions between the functionalized metallic substrate, multipurpose coating, and biological environment (tissue) that is in contact with the functionalized material can only be obtained by using state-of-the-art interdisciplinary techniques and characterization approaches. For this reason, we use a combination of methods from very different scientific fields, which gives us much deeper insight into the properties of new materials and their potential capabilities. We are paving the way to a new approach to the evaluation of medical grade metal materials intended for biomedical applications (and possibly others) by combining various characterization methods, ranging from chemical, physical, and biological, to the functional testing of the desired material properties related to actual use. We believe that this approach could represent an appropriate platform for the future evaluation of similar materials.

Our research consists of the following stages:

  1. Obtaining data on the surface properties of newly developed multilayer coatings on metal substrates by AFM, FE-SEM, ToF-SIMS, XPS, EDX, and contact angle measurements. (The final combination of the listed techniques depends on the properties of the individual systems.)
  2. The evaluation of the structural characteristics of individual layers by means of ATR-FTIR measurements, as well as beam deflection spectrometry (BDS).
  3. Estimating the corrosion susceptibility of these systems in a simulated targeted environment (0.9 wt.% NaCl solution) by electrochemical techniques, including electrochemical impedance spectroscopy (EIS) and cyclic polarisation (CP).
  4. Evaluating the potential interaction of these systems with relevant human cells (based on tetrazolium salt MTT and Live/Dead assays).
  5. Obtaining data on capability as regards controlled drug release using in vitro drug release performance testing. Thorough statistical evaluation is conducted in every step of the research.

We have found that the approach proposed (a combination of methods from very different scientific fields) yields far deeper insights into the properties and potential performance of the material. Although the list of the methods used could be extended, we believe that the proposed combination is the necessary basis for the analysis of metal substrates for orthopaedic implants that have potential for clinical use in the future. All studies of the newly developed materials are based on the approach presented above. However, some adjustments are made according to the characteristics of the individual systems studied.

We believe that the multifunctional bioactive coatings developed in this project have great potential to improve the currently used orthopaedic metal materials. The results of our preliminary studies show that such systems might not only extend the lifespan of medical implants, but also reduce post-operative infection, stimulate cell attachment, and facilitate the fixation of an implant. Moreover, multifunctional bioactive coatings enable the delivery of the incorporated therapeutic agents in a controlled manner, thereby allowing the desired therapy. Medical implants with such combination of characteristics would significantly reduce the cost of treatment and drastically increase the quality of patients’ lives.

Project Stages

  1. The formulation and characterization of the basic material
  2. The preparation of the bioactive coatings
  3. Corrosion testing
  4. Interaction studies regarding the coated substrate materials and cells
  5. Biocompatibility studies
  6. Preclinical efficacy testing

References

The most important research findings were published in the following original scientific articles:

  1. BRAČIČ, Matej, POTRČ, Sanja, FINŠGAR, Matjaž, GRADIŠNIK, Lidija, MAVER, Uroš, BUDASHEVA, Hanna, KORTE, Dorota, FRANKO, Mladen, FRAS ZEMLJIČ, Lidija. Amoxicillin doped hyaluronic acid/fucoidan multifunctional coatings for medical grade stainless steel orthopedic implants. Applied Surface Science. [Print ed.]. 2023, vol. 611, part a, str. 1-11, ilustr. ISSN 0169-4332. DOI: 10.1016/j.apsusc.2022.155621. [COBISS.SI-ID 130119171], [JCR, SNIP]
  2. FINŠGAR, Matjaž. The interface characterization of 2-Mercapto-1-methylimidazole corrosion inhibitor on brass. Coatings. 4 March 2021, vol. 11, iss. 3, str. 1-18, ilustr. ISSN 2079-6412. https://www.mdpi.com/2079-6412/11/3/295, DOI: 10.3390/coatings11030295. [COBISS.SI-ID 53959171], [JCR, SNIP, WoS]
  3. MAVER, Tina, MASTNAK, Tinkara, MIHELIČ, Mihela, MAVER, Uroš, FINŠGAR, Matjaž. Clindamycin-based 3D-printed and electrospun coatings for treatment of implant-related infections. Materials. 17 March 2021, vol. 14, iss. 6, str. 1-17. ISSN 1996-1944. https://www.mdpi.com/1996-1944/14/6/1464, DOI: 10.3390/ma14061464. [COBISS.SI-ID 55568899], [JCR, SNIP, WoS]
  4. FINŠGAR, Matjaž, PERVA-UZUNALIĆ, Amra, BEHR, Heiko, LEDINEK, Nina, KNEZ, Željko, NOVAK, Zoran. An improved reversed-phase high-performance liquid chromatography method for the analysis of related substances of prednisolone in active ingredient. ACS omega. 2020, vol. 5, no. 14, str. 7987-8000, ilustr. ISSN 2470-1343. DOI: 10.1021/acsomega.0c00037. [COBISS.SI-ID 23091478], [JCR, SNIP, WoS]
  5. FINŠGAR, Matjaž. Surface analysis of the 2-mercaptobenzothiazole corrosion inhibitor on 6082 aluminum alloy using ToF-SIMS and XPS. Analytical methods. 2020, vol. 12, no. 4, str. 456-465. ISSN 1759-9660. DOI: 10.1039/C9AY02293G. [COBISS.SI-ID 22869526], [JCR, SNIP, WoS]
  6. MAVER, Uroš, XHANARI, Klodian, ŽIŽEK, Marko, GRADIŠNIK, Lidija, REPNIK, Katja, POTOČNIK, Uroš, FINŠGAR, Matjaž. Carboxymethyl cellulose/diclofenac bioactive coatings on AISI 316LVM for controlled drug delivery, and improved osteogenic potential. Carbohydrate polymers. [Print ed.]. 15 Feb. 2020, vol. 230, str. 1-13. ISSN 0144-8617. DOI: 10.1016/j.carbpol.2019.115612. [COBISS.SI-ID 22749718], [JCR, SNIP, WoS]
  7. AJDNIK, Urban, FINŠGAR, Matjaž, FRAS ZEMLJIČ, Lidija. Characterization of chitosan-lysine surfactant bioactive coating on silicone substrate. Carbohydrate polymers. [Print ed.]. 15 March 2020, vol. 232, str. 1-10, ilustr. ISSN 0144-8617. DOI: 10.1016/j.carbpol.2019.115817. [COBISS.SI-ID 22920470], [JCR, SNIP, WoS]
  8. FINŠGAR, Matjaž. Electrochemical, 3D topography, XPS, and ToF-SIMS analyses of 4-methyl-2-phenylimidazole as a corrosion inhibitor for brass. Corrosion science. [Print ed.]. June 2020, vol. 169, str. 1-12. ISSN 0010-938X. DOI: 10.1016/j.corsci.2020.108632. [COBISS.SI-ID 23106582], [JCR, SNIP, WoS]
  9. FINŠGAR, Matjaž, JEZERNIK, Klara. The use of factorial design and simplex optimization to improve analytical performance of in situ film electrodes. Sensors. 2020, vol. 20, iss. 14, str. 1-22. ISSN 1424-8220. DOI: 10.3390/s20143921. [COBISS.SI-ID 22572035], [JCR, SNIP, WoS]
  10. MAVER, Tina, MOHAN, Tamilselvan, GRADIŠNIK, Lidija, FINŠGAR, Matjaž, STANA-KLEINSCHEK, Karin, MAVER, Uroš. Polysaccharide thin solid films for analgesic drug delivery and growth of human skin cells. Frontiers in chemistry. [Online ed.]. 9 April 2019, vol. 7, str. 1-13. ISSN 2296-2646. DOI: 10.3389/fchem.2019.00217. [COBISS.SI-ID 22236950], [JCR, SNIP, WoS]
  11. FINŠGAR, Matjaž, XHANARI, Klodian, PETOVAR, Barbara. A comparison of hydrochloric acid and acetate buffer media for trace metal analysis using sb-film electrodes : a detailed electrochemical impedance spectroscopy study. Journal of the Electrochemical Society. [Online ed.]. 2019, vol. 166, iss. 4, str. h108-h118. ISSN 1945-7111. DOI: 10.1149/2.0191904jes. [COBISS.SI-ID 22142486], [JCR, SNIP, WoS]
  12. FINŠGAR, Matjaž, PETOVAR, Barbara, VODOPIVEC, Katja. Bismuth-tin-film electrodes for Zn(II), Cd(II), and Pb(II) trace analysis. Microchemical journal. [Print ed.]. March 2019, vol. 145, str. 676-685. ISSN 0026-265X. DOI: 10.1016/j.microc.2018.11.036. [COBISS.SI-ID 21896982], [JCR, SNIP, WoS]
  13. FINŠGAR, Matjaž, XHANARI, Klodian, PETOVAR, Barbara. Copper-film electrodes for Pb(II) trace analysis and a detailed electrochemical impedance spectroscopy study. Microchemical journal. [Print ed.]. June 2019, vol. 147, str. 863-871. ISSN 0026-265X. DOI: 10.1016/j.microc.2019.04.007. [COBISS.SI-ID 22244630], [JCR, SNIP, WoS]
  14. FINŠGAR, Matjaž, RISTIĆ, Tijana, FARDIM, Pedro, FRAS ZEMLJIČ, Lidija. Time-of-flight secondary ion mass spectrometry analysis of chitosan-treated viscose fibres. Analytical biochemistry. 15 Sept. 2018, vol. 557, str. 131-141, ilustr. ISSN 0003-2697. DOI: 10.1016/j.ab.2018.07.021. [COBISS.SI-ID 21593878], [JCR, SNIP, WoS]
  15. FINŠGAR, Matjaž, PETOVAR, Barbara. Novel in situ Bi-Sb-film electrode for trace heavy metal analysis. Electroanalysis. [Online ed.]. Nov. 2018, vol. 30, iss. 11, str. 2781-2792. ISSN 1521-4109. DOI: 10.1002/elan.201800545. [COBISS.SI-ID 21692438], [JCR, SNIP, WoS]
  16. KOVAČ, Janez, FINŠGAR, Matjaž. Analysis of the thermal stability of very thin surface layers of corrosion inhibitors by time-of-flight secondary ion mass spectrometry. Journal of the American Society for Mass Spectrometry. [Print ed.]. Dec. 2018, vol. 29, iss. 12, str. 2305-2316. ISSN 1044-0305. DOI: 10.1007/s13361-018-2048-1. [COBISS.SI-ID 21645334], [JCR, SNIP, WoS]
  17. FINŠGAR, Matjaž, MAJER, David, MAVER, Uroš, MAVER, Tina. Reusability of SPE and Sb-modified SPE sensors for trace Pb(II) determination. Sensors. 2018, vol. 18, no. 11, str. 1-16, ilustr. ISSN 1424-8220. DOI: 10.3390/s18113976. [COBISS.SI-ID 21869334], [JCR, SNIP, WoS]