The search for the ideal metallic material for an implant is still a difficult challenge for scientists due to the phenomenon of corrosion and the consequent disruption of the implant structure. Prevention is the application of coatings that protect the implant, activate the tissues for faster regeneration, and also prevent inflammation through antibacterial and antiviral effects. The present study focuses on the selection of components for a Ti-6Al-4V alloy coating. These days, researchers are taking an intense interest in extracts of natural origin. It was decided to take a look at Sideritis raeseri, which contains vitamins and valuable elements and is rich in polyphenols, as well as antioxidants. The composition of coatings based on a PEG polymer reinforced with brushite and the S. raeseri extract with the proteins L-carnosine, fibroin, or sericin was developed. The samples were subjected to detailed physiochemical analysis, including potentiometry and electrical conductivity analysis, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis, and UV-VIS spectroscopy. The study demonstrated that polyphenols were successfully released from the coatings during incubation in vitro. The osteointegration process can be supported by a number of factors, such as the release of polyphenols from implant coatings to prevent bacterial, viral, and fungal infections. Subjecting the samples to 14 days of incubation demonstrated their interactions with the incubation fluids, an ion exchange between the medium and the materials. An analysis of the surface morphology exhibited the presence of brushite crystals and their increased number after incubation, indicating the bioactivity of the formed coatings.

Department of Analytical Chemistry Faculty of Natural Sciences Comenius University Ilkovicova 6 842 15 Bratislava Slovakia

Department of Chemical Biology Faculty of Science Palacky University Olomouc Slechtitelu 27 783 71 Olomouc Czech Republic

Department of Materials Science Faculty of Materials Engineering and Physics Cracow University of Technology 37 Jana Pawła 2 Av 31 864 Krakow Poland

See more in PubMed

Ran Q., Yang W., Hu Y., Shen X., Yu Y., Xiang Y., Cai K. Osteogenesis of 3D Printed Porous Ti6Al4V Implants with Different Pore Sizes. J. Mech. Behav. Biomed. Mater. 2018;84:1–11. doi: 10.1016/j.jmbbm.2018.04.010. PubMed DOI

Quinn J., McFadden R., Chan C.W., Carson L. Titanium for Orthopedic Applications: An Overview of Surface Modification to Improve Biocompatibility and Prevent Bacterial Biofilm Formation. iScience. 2020;23:101745. doi: 10.1016/j.isci.2020.101745. PubMed DOI PMC

Siti Nur Hazwani M.R., Lim L.X., Lockman Z., Zuhailawati H. Fabrication of Titanium-Based Alloys with Bioactive Surface Oxide Layer as Biomedical Implants: Opportunity and Challenges. Trans. Nonferrous Met. Soc. China (Engl. Ed.) 2022;32:1–44. doi: 10.1016/S1003-6326(21)65776-X. DOI

Durdu S., Usta M., Berkem A.S. Bioactive Coatings on Ti6Al4V Alloy Formed by Plasma Electrolytic Oxidation. Surf. Coat. Technol. 2016;301:85–93. doi: 10.1016/j.surfcoat.2015.07.053. DOI

Haydar H.J., Al-Deen J., Abidali A.K., Mahmoud A.A. Improved Performance of Ti6Al4V Alloy in Biomedical Applications—Review. J. Phys. Conf. Ser. 2021;1973:012146. doi: 10.1088/1742-6596/1973/1/012146. DOI

Daruich De Souza C., Ribeiro Nogueira B., Rostelato M.E.C.M. Review of the Methodologies Used in the Synthesis Gold Nanoparticles by Chemical Reduction. J. Alloys Compd. 2019;798:714–740. doi: 10.1016/J.JALLCOM.2019.05.153. DOI

Boanini E., Silingardi F., Gazzano M., Bigi A. Synthesis and Hydrolysis of Brushite (DCPD): The Role of Ionic Substitution. Cryst. Growth Des. 2021;21:1689–1697. doi: 10.1021/acs.cgd.0c01569. DOI

Pina S., Vieira S.I., Rego P., Torres P.M.C., da Cruz e Silva O.A.B., da Cruz e Silva E.F., Ferreira J.M.F. Biological Responses of Brushite-Forming Zn-and ZnSr-Substituted β-Tricalcium Phosphate Bone Cements. Eur. Cells Mater. 2010;20:162–177. doi: 10.22203/eCM.v020a14. PubMed DOI

Türk S., Altınsoy, ÇelebiEfe G., Ipek M., Özacar M., Bindal C. Biomimetric Coating of Monophasic Brushite on Ti6Al4V in New M-5xSBF. Surf. Coat. Technol. 2018;351:1–10. doi: 10.1016/J.SURFCOAT.2018.07.067. DOI

Giocondi J.L., El-Dasher B.S., Nancollas G.H., Orme C.A. Molecular Mechanisms of Crystallization Impacting Calcium Phosphate Cements. Trans. R. Soc. A. 2010;368:1937–1961. doi: 10.1098/rsta.2010.0006. PubMed DOI PMC

Kolagenowych S. Ph.D. Thesis. Uniwersytet Jagielloński; Kraków, Poland: 2018. Fizykochemiczna Charakterystyka Mineralizacji Struktur Kolagenowych.

Ebnesajjad S. Handbook of Biopolymers and Biodegradable Plastics. Elsevier Science; Amsterdam, The Netherlands: 2013.

Preedy V.R. Diabetes: Oxidative Stress and Dietary Antioxidants. Academic Press; Cambridge, MA, USA: 2020.

Patel V., Rajendram R. The Liver: Oxidative Stress and Dietary Antioxidants. Academic Press; Cambridge, MA, USA: 2018.

Julien E., Coulon-Bublex M., Garel A., Royer C., Chavancy G., Prudhomme J.C., Couble P. Comprehensive Molecular Insect Science. Pergamon; Bergama, Turkey: 2005.

Bilska-Wilkosz A., Iciek M., Kowalczyk-Pachel D. Biochemia z Elementami Chemii Biologicznej Dla Inżynierów. Politechnika Krakowska; Kraków, Poland: 2015.

Manoukian O., Sardashti T., Gailiunas K., Ojha A., Penalosa A., Mancuso C., Hobert M., Kumbar S. Encyclopedia Od Biomedical Engineering. Volume 1 Elsevier; Amsterdam, The Netherlands: 2019.

Silva S.S., Fernandes E., Pina S., Silva-Correia J., Vieira S., Oliveira J., Reis R. Comprehensive Biomaterials II, Reference Module in Materials Science and Materials Engineering. Volume 2 Elsevier; Amsterdam, The Netherlands: 2017.

Liu J., Shi L., Deng Y., Zou M., Cai B., Song Y., Wang Z., Wang L. Silk Sericin-Based Materials for Biomedical Applications. Biomaterials. 2022;287:121638. doi: 10.1016/J.BIOMATERIALS.2022.121638. PubMed DOI

Ahsan F., Ansari T.M., Usmani S., Bagga P. An Insight on Silk Protein Sericin: From Processing to Biomedical Application. Drug Res. 2018;68:317–327. doi: 10.1055/s-0043-121464. PubMed DOI

Gobbo V.A. Master’s Thesis. Politecnico di Torino; Torino, Italy: 2020. Bioaterials Fuctionalisation with Polyphenols and Characterisation.

Anli R.E., Vural N. Antioxidant Phenolic Substances of Turkish Red Wines from Different Wine Regions. Molecules. 2009;14:289–297. doi: 10.3390/molecules14010289. PubMed DOI PMC

Kosiorek A., Oszmiański J., Golański J. Podstawy Do Zastosowania Polifenoli Roślinnych Jako Nutraceutyków o Właściwościach Przeciwpyłkowych. Postępy Fitoter. 2013;2:108–117.

Gao X., Xu Z., Liu G., Wu J. Polyphenols as a Versatile Component in Tissue Engineering. Acta Biomater. 2021;119:57–74. doi: 10.1016/J.ACTBIO.2020.11.004. PubMed DOI

El Gharras H. Polyphenols: Food Sources, Properties and Applications—A Review. Int. J. Food Sci. Technol. 2009;44:2512–2518. doi: 10.1111/j.1365-2621.2009.02077.x. DOI

Rufino A.T., Costa V.M., Carvalho F., Fernandes E. Flavonoids as Antiobesity Agents: A Review. Med. Res. Rev. 2021;41:556–585. doi: 10.1002/med.21740. PubMed DOI

Chen L., Cao H., Huang Q., Xiao J., Teng H. Absorption, Metabolism and Bioavailability of Flavonoids: A Review. Crit. Rev. Food Sci. Nutr. 2022;62:7730–7742. doi: 10.1080/10408398.2021.1917508. PubMed DOI

Drinić Z., Pljevljakušić D., Janković T., Zdunić G., Bigović D., Šavikin K. Hydro-Distillation and Microwave-Assisted Distillation of Sideritis raeseri: Comparison of the Composition of the Essential Oil, Hydrolat and Residual Water Extract. Sustain. Chem. Pharm. 2021;24:100538. doi: 10.1016/J.SCP.2021.100538. DOI

Gabrieli C.N., Kefalas P.G., Kokkalou E.L. Antioxidant Activity of Flavonoids from Sideritis raeseri. J. Ethnopharmacol. 2005;96:423–428. doi: 10.1016/j.jep.2004.09.031. PubMed DOI

Żyżelewicz D., Kulbat-Warycha K., Oracz J., Żyżelewicz K. Polyphenols and Other Bioactive Compounds of Sideritis Plants and Their Potential Biological Activity. Molecules. 2020;25:3763. doi: 10.3390/molecules25163763. PubMed DOI PMC

Romanucci V., Di Fabio G., D’Alonzo D., Guaragna A., Scapagnini G., Zarrelli A. Traditional Uses, Chemical Composition and Biological Activities of Sideritis raeseri Boiss. & Heldr. J. Sci. Food Agric. 2017;97:373–383. doi: 10.1002/jsfa.7867. PubMed DOI

Khalil I., Alanazi A., Aldhafeeri K.A., Alamer O., Alshaaer M. Crystallization and Applications. IntechOpen; London, UK: 2022. Brushite: Synthesis, Properties, and Biomedical Applications. DOI

Slota D., Gląb M., Tyliszczak B., Dogulas T.E.L., Rudnicka K., Miernik K., Urbaniak M.M., Rusek-Wala P., Sobczak-upiec A. Composites Based on Hydroxyapatite and Whey Protein Isolate for Applications in Bone Regeneration. Materials. 2021;14:2317. doi: 10.3390/ma14092317. PubMed DOI PMC

Słota D., Florkiewicz W., Piętak K., Pluta K., Sadlik J., Miernik K., Sobczak-Kupiec A. Preparation of PVP and Betaine Biomaterials Enriched with Hydroxyapatite and Its Evaluation as a Drug Carrier for Controlled Release of Clindamycin. Ceram. Int. 2022;48:35467–35473. doi: 10.1016/j.ceramint.2022.08.151. DOI

Słota D., Florkiewicz W., Piętak K., Szwed A., Włodarczyk M., Siwińska M., Rudnicka K., Sobczak-Kupiec A. Preparation, Characterization, and Biocompatibility Assessment of Polymer-Ceramic Composites Loaded with Salvia Officinalis Extract. Materials. 2021;14:6000. doi: 10.3390/ma14206000. PubMed DOI PMC

Gilewska G. Przydatność Różnych Technik Obrazowania Struktur Biologicznych Wykorzystujących Elektronowy Mikroskop Skaningowy. Pr. Inst. Elektrotechniki. 2010;244:161–169.

Moseke C., Bayer C., Vorndran E., Barralet J.E., Groll J., Gbureck U. Low Temperature Fabrication of Spherical Brushite Granules by Cement Paste Emulsion. J. Mater. Sci. Mater. Med. 2012;23:2631–2637. doi: 10.1007/s10856-012-4740-1. PubMed DOI

Binitha M.P., Pradyumnan P.P. Dielectric Property Studies of Biologically Compatible Brushite Single Crystals Used as Bone Graft Substitute. J. Biomater. Nanobiotechnol. 2013;04:119–122. doi: 10.4236/jbnb.2013.42016. DOI

Joseph K.C., Jethva H.O., Jogiya B., Chauhan C.K., Vaidya A.D.B., Joshi M.J. In Vitro Growth Inhibition Study of Urinary Type Brushite Crystals in the Presence of Healthy Adult Urine and Tartaric Acid. IOSR J. Pharm. Biol. Sci. 2017;12:47–53.

Sadlik J., Kosińska E., Słota D., Niziołek K., Tomala A., Włodarczyk M., Piątek P., Skibiński J., Jampilek J., Sobczak-Kupiec A. Bioactive Hydrogel Based on Collagen and Hyaluronic Acid Enriched with Freeze-Dried Sheep Placenta for Wound Healing Support. Int. J. Mol. Sci. 2024;25:1687. doi: 10.3390/ijms25031687. PubMed DOI PMC

Trpkovska M., Šoptrajanov B., Malkov P. FTIR Reinvestigation of the Spectra of Synthetic Brushite and Its Partially Deuterated Analogues. J. Mol. Struct. 1999;480–481:661–666. doi: 10.1016/S0022-2860(98)00923-5. DOI

Zhang X.M., Wyeth P. Using FTIR Spectroscopy to Detect Sericin on Historic Silk. Sci. China Chem. 2010;53:626–631. doi: 10.1007/s11426-010-0050-y. DOI

Koperska M.A., Pawcenis D., Bagniuk J., Zaitz M.M., Missori M., Łojewski T., Łojewska J. Degradation Markers of Fibroin in Silk through Infrared Spectroscopy. Polym. Degrad. Stab. 2014;105:185–196. doi: 10.1016/j.polymdegradstab.2014.04.008. DOI

Durmus Z., Kavas H., Baykal A., Sozeri H., Alpsoy L., Elik S.Ü., Toprak M.S. Synthesis and Characterization of L-Carnosine Coated Iron Oxide Nanoparticles. J. Alloys Compd. 2011;509:2555–2561. doi: 10.1016/j.jallcom.2010.11.088. DOI

Farid R.M., Gaafar P.M.E., Hazzah H.A., Helmy M.W., Abdallah O.Y. Chemotherapeutic Potential of L-Carnosine from Stimuli-Responsive Magnetic Nanoparticles against Breast Cancer Model. Nanomedicine. 2020;15:891–911. doi: 10.2217/nnm-2019-0428. PubMed DOI

Saidi M., Dabbaghi A., Rahmani S. Swelling and Drug Delivery Kinetics of Click-Synthesized Hydrogels Based on Various Combinations of PEG and Star-Shaped PCL: Influence of Network Parameters on Swelling and Release Behavior. Polym. Bull. 2020;77:3989–4010. doi: 10.1007/s00289-019-02948-z. DOI

Dominguez-López I., Pérez M., Lamuela-Raventós R.M. Total (Poly)Phenol Analysis by the Folin-Ciocalteu Assay as an Anti-Inflammatory Biomarker in Biological Samples. Crit. Rev. Food Sci. Nutr. 2023:1–7. doi: 10.1080/10408398.2023.2220031. PubMed DOI PMC

Pérez M., Dominguez-López I., Lamuela-Raventós R.M. The Chemistry Behind the Folin-Ciocalteu Method for the Estimation of (Poly)Phenol Content in Food: Total Phenolic Intake in a Mediterranean Dietary Pattern. J. Agric. Food Chem. 2023;71:17543–17553. doi: 10.1021/acs.jafc.3c04022. PubMed DOI PMC

Erdoğan M., Polat Köse L., Eşsiz S., Gülçin İ. Synthesis and Biological Evaluation of Some 1-Naphthol Derivatives as Antioxidants, Acetylcholinesterase, and Carbonic Anhydrase Inhibitors. Arch. Pharm. 2021;354:2100113. doi: 10.1002/ardp.202100113. PubMed DOI

Gulcin İ., Alwasel S.H. DPPH Radical Scavenging Assay. Processes. 2023;11:2248. doi: 10.3390/pr11082248. DOI

Yanchev N., Petkova N., Ivanov I., Delev D. Total Polyphenolic Content and Antioxidant Activity of Different Extracts from Sideritis Scardica. Trop. J. Nat. Prod. Res. 2022;6:528–533. doi: 10.26538/tjnpr/v6i7.12. DOI

Koleva I.I., Linssen J.P.H., Van Beek T.A., Evstatieva L.N., Kortenska V., Handjieva N. Antioxidant Activity Screening of Extracts from Sideritis Species (Labiatae) Grown in Bulgaria. J. Sci. Food Agric. 2003;83:809–819. doi: 10.1002/jsfa.1415. DOI