J1-2470: Biofunctionalization of 3D-printed metal alloys as a newly emerging strategy to diminish undesired effects of orthopedic implants

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


Project Description

Developing strategies and solutions to avoid or minimize undesired side effects in the use of medical implants is still a partially unsolved challenge. In the early stage of healing, the body’s initial response to foreign material manifests as inflammation, which can range from minimal local inflammation to an extensive and chronic foreign body reaction. A factor that crucially influences the success of healing during this stage is the implant’s surface properties. The ultimate goal is that recognition of the implant as a foreign body is impaired, usually by the careful choice of the external layer, thus minimizing the initial inflammatory cell response. The selection of scaffold materials and their architectural design play a very complex yet critical role in promoting bone regeneration by providing mimicry of the native bone matrix. Evidence suggests that modifying the implant surface in order for it to better resemble the extracellular matrix of healthy tissues results in the increased osteointegration and osteoinduction of the implant.

3D-printing enables the fabrication of complex structures ideally matched to the needs of each patient that take into account the patient-specific damage and minimize bone loss due to the implantation requirements, while providing surfaces that more closely resemble the specific anatomy of the bone. Moreover, the use of customized surgical items has been shown to markedly reduce surgical time, and to enhance the medical outcome of the surgery, thus reducing the length of the hospital stay.

Wear, corrosion, and exposure to a changing environment after a long period of time lead to macroscopic and microscopic changes in the metal implant material. Consequently, many unexpected consequences for the surrounding tissues can occur, making the healthy environment of the implant vulnerable to infection. Advanced coatings can achieve the synergistic effect of bioactivity and high mechanical strength. More importantly, such coatings can protect the alloys by mitigating corrosion as a barrier against the release of metal ions into a highly corrosive biological environment.

Effective therapy can only be provided by the controlled drug release of all of the therapeutic agents. Whereas some drugs provide a desired release profile (i.e. their variable solubility leads to different release profiles over time), controlled drug release vehicles are usually required. The controlled release of therapeutic agents is even more important in multidrug formulations, since these have to provide multimodal therapy as regards space and time. The carrier materials for the active substances have to be biodegradable, yet sufficiently extensive knowledge regarding the interaction of the material components with the environment is often not available. Through detailed interaction studies, the mechanical and release kinetics can be clearly understood and used as fundamental knowledge to optimize the use of materials, and hence render the therapy safer, as well as effective.

The objective of this project proposal is to develop novel bioactive multifunctional coatings on 3D-printed metal alloy substrates for orthopaedic implants. The proposed project builds and upgrades the existing knowledge, and also provides completely novel solutions regarding the coating preparation, thus achieving the coating’s bioactivity, and the multifunctionality of the final material. The aim of each surgical procedure is to use the most efficient implant with the longest possible life span, and the best biocompatibility. This can only be accomplished by adapting the implant to the patient’s individual needs. Our approach promises to develop an “all-in-one” treatment that could provide the following benefits:

  • the decreased possibility of the rejection of the artificial implant due to anti-inflammatory action;
  • the prevention of infections during or after surgery;
  • lower systemic risk of thromboembolic events; and
  • the growth promotion of the desired osteoblasts due to either the chosen materials or the incorporated therapeutic agents.

Project Stages

  1. The preparation of 3D-printed materials with enhanced chemical and metallurgical properties
  2. Basic material formulation, followed by the systematic characterization of its properties
  3. The preparation of novel complex and multifunctional bioactive coatings followed by their integration onto substrates
  4. Corrosion tests
  5. A study of the interaction phenomena in model and in vitro systems;
  6. Evaluation of: i) the physicochemical, ii) structural and morphological, and iii) bioactive functionality of the coated surfaces
  7. Biocompatibility studies and preclinical efficacy testing


  1. Kravanja, K.A. and M. Finšgar, A review of techniques for the application of bioactive coatings on metal-based implants to achieve controlled release of active ingredients. Materials & Design, 2022: p. 110653.
  2. Bjelić, D. and M. Finšgar, The role of growth factors in bioactive coatings. Pharmaceutics, 2021. 13(7): p. 1083.
  3. Mastnak, T., U. Maver, and M. Finšgar, Addressing the Needs of the Rapidly Aging Society through the Development of Multifunctional Bioactive Coatings for Orthopedic Applications. International Journal of Molecular Sciences, 2022. 23(5): p. 2786.
  4. Marovič, N., et al., Magnetic nanoparticles in 3D-printed scaffolds for biomedical applications. Nanotechnology Reviews, 2023. 12(1).
  5. Pal, S., et al., Effect of surface powder particles and morphologies on corrosion of Ti-6Al-4 V fabricated with different energy densities in selective laser melting. Materials & Design, 2021. 211: p. 110184.
  6. Leban, M.B., T. Kosec, and M. Finšgar, Corrosion characterization and ion release in SLM-manufactured and wrought Ti6Al4V alloy in an oral environment. Corrosion Science, 2022. 209: p. 110716.
  7. Drstvenšek, I., et al., Influence of local heat flow variations on geometrical deflections, microstructure, and tensile properties of Ti-6Al-4 V products in powder bed fusion systems. Journal of Manufacturing Processes, 2021. 65: p. 382-396.
  8. Bajt Leban, M., T. Kosec, and M. Finšgar, The corrosion resistance of dental Ti6Al4V with differing microstructures in oral environments. Journal of Materials Research and Technology, 2023. 27: p. 1982-1995.
  9. Pal, S., et al., Mechanisms of defect formation in Ti-6Al-4V product during re-melting of layers in selective laser melting. Journal of Manufacturing Processes, 2023. 105: p. 260-275.
  10. Maver, T., et al., Clindamycin-based 3D-printed and electrospun coatings for treatment of implant-related infections. Materials, 2021. 14(6): p. 1464.
  11. Kravanja, K.A., et al., Evaluation of Natural Extracts as Promising Components of Bioactive Coatings for Orthopedic Implants. Frontiers in Materials, 2022. 9: p. 878176.
  12. Bjelić, D. and M. Finšgar, Bioactive coatings with anti-osteoclast therapeutic agents for bone implants: Enhanced compliance and prolonged implant life. Pharmacological Research, 2022: p. 106060.
  13. Kravanja, K.A., et al., Supercritical Fluid Technologies for the Incorporation of Synthetic and Natural Active Compounds into Materials for Drug Formulation and Delivery. Pharmaceutics, 2022. 14(8): p. 1670.
  14. Rožanc, J., et al., Dexamethasone-loaded bioactive coatings on medical grade stainless steel promote osteointegration. Pharmaceutics, 2021. 13(4): p. 568.
  15. Finšgar, M., J. Kovač, and U. Maver, The development and characterization of bioactive coatings for local drug delivery in orthopedic applications. Progress in Organic Coatings, 2021. 158: p. 106350.
  16. Bračič, M., et al., Amoxicillin doped hyaluronic acid/fucoidan multifunctional coatings for medical grade stainless steel orthopedic implants. Applied Surface Science, 2023. 611: p. 155621.
  17. Kravanja, K.A., et al., Ketoprofen-loaded PLGA-based bioactive coating prepared by supercritical foaming on a TiAl6V4 substrate for local drug delivery in orthopedic applications. Progress in Organic Coatings, 2024. 186: p. 108026.
  18. Pantić, M., et al., Evaluation of ethanol-induced chitosan aerogels with human osteoblast cells. International Journal of Biological Macromolecules, 2023. 253: p. 126694.
  19. Kravanja, K.A., et al., The synthesis, surface analysis, and cellular response of titania and titanium oxynitride nanotube arrays prepared on TiAl6V4 for potential biomedical applications. Journal of Materials Research and Technology, 2023. 24: p. 4074-4090.
  20. Finšgar, M., Advanced surface analysis using GCIB-C60++-tandem-ToF-SIMS and GCIB-XPS of 2-mercaptobenzimidazole corrosion inhibitor on brass. Microchemical Journal, 2020. 159: p. 105495.
  21. Finšgar, M., Surface analysis and interface properties of 2-aminobenzimidazole corrosion inhibitor for brass in chloride solution. Analytical and Bioanalytical Chemistry, 2020. 412(30): p. 8431-8442.
  22. Finšgar, M., The influence of the amino group in 3‐amino‐1, 2, 4‐triazole corrosion inhibitor on the interface properties for brass studied by ToF‐SIMS. Rapid Communications in Mass Spectrometry, 2021. 35(7): p. e9056.
  23. Finšgar, M., Time‐of‐flight secondary ion mass spectrometry and X‐ray photoelectron spectroscopy study of 2‐phenylimidazole on brass. Rapid Communications in Mass Spectrometry, 2021. 35(2): p. e8974.
  24. Finšgar, M., The interface characterization of 2-mercapto-1-methylimidazole corrosion inhibitor on brass. Coatings, 2021. 11(3): p. 295.
  25. Majer, D. and M. Finšgar, An l-cysteic acid-modified screen-printed carbon electrode for methyl parathion determination. Microchemical Journal, 2022. 183: p. 108098.
  26. Kravanja, K.A. and M. Finšgar, Analytical Techniques for the Characterization of Bioactive Coatings for Orthopaedic Implants. Biomedicines, 2021. 9(12): p. 1936.
  27. Finšgar, M., Surface analysis by gas cluster ion beam XPS and ToF-SIMS tandem MS of 2-mercaptobenzoxazole corrosion inhibitor for brass. Corrosion Science, 2021. 182: p. 109269.
  28. Žurga, N., D. Majer, and M. Finšgar, Pb (II) Determination in a Single Drop Using a Modified Screen-Printed Electrode. Chemosensors, 2021. 9(2): p. 38.
  29. Bukovec, M., K. Xhanari, and M. Finšgar, Development and analysis of frits for enamelling AA2024, AA6082 and AA7075 aluminium alloys. Materials and Corrosion, 2021. 72(4): p. 660-671.
  30. Zidarič, T., et al., The development of an electropolymerized, molecularly imprinted polymer (MIP) sensor for insulin determination using single-drop analysis. Analyst, 2023. 148(5): p. 1102-1115.
  31. Majer, D. and M. Finšgar, Single-drop analysis of epinephrine and uric acid on a screen-printed carbon electrode. Biosensors, 2021. 11(8): p. 285.
  32. Majer, D., T. Mastnak, and M. Finšgar, An Advanced Statistical Approach Using Weighted Linear Regression in Electroanalytical Method Development for Epinephrine, Uric Acid and Ascorbic Acid Determination. Sensors, 2020. 20(24): p. 7056.
  33. Rožanc, J., et al., Mesenchymal Stem Cells Isolated from Paediatric Paravertebral Adipose Tissue Show Strong Osteogenic Potential. Biomedicines, 2022. 10(2): p. 378.
  34. Gradišnik, L., et al., The Endplate Role in Degenerative Disc Disease Research: The Isolation of Human Chondrocytes from Vertebral Endplate—An Optimised Protocol. Bioengineering, 2022. 9(4): p. 137.
  35. Rožanc, J., M. Finšgar, and U. Maver, Progressive use of multispectral imaging flow cytometry in various research areas. Analyst, 2021. 146(16): p. 4985-5007.
  36. Vihar, B., et al., Investigating the Viability of Epithelial Cells on Polymer Based Thin-Films. Polymers, 2021. 13(14): p. 2311.
  37. Pal, S., et al., Fine martensite and beta-grain variational effects on mechanical properties of Ti–6Al–4V while laser parameters change in laser powder bed fusion. Materials Science and Engineering: A, 2024. 892: p. 146052.