Bioactive calcium phosphate ceramics (CaPs) are one of the building components of the inorganic part of bones. Synthetic CaPs are frequently used as materials for filling bone defects in the form of pastes or composites; however, their porous structure allows modification with active substances and, thus, subsequent use as a drug carrier for the controlled release of active substances. In this study, four different ceramic powders were compared: commercial hydroxyapatite (HA), TCP, brushite, as well as HA obtained by wet precipitation methods. The ceramic powders were subjected to physicochemical analysis, including FTIR, XRD, and determination of Ca/P molar ratio or porosity. These techniques confirmed that the materials were phase-pure, and the molar ratios of calcium and phosphorus elements were in accordance with the literature. This confirmed the validity of the selected synthesis methods. CaPs were then modified with the antibiotic clindamycin. Drug release was determined on HPLC, and antimicrobial properties were tested against Staphylococcus aureus. The specific surface area of the ceramic has been demonstrated to be a factor in drug release efficiency.

Bio Med Chem Doctoral School University of Lodz and Lodz Institutes of the Polish Academy of Sciences 90 237 Łódź Poland

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

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

Department of Immunology and Infectious Biology Faculty of Biology and Environmental Protection University of Łódź 90 237 Łódź Poland

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

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Zang S., Chang S., Shahzad M.B., Sun X., Jiang X., Yang H. Ceramics-based Drug Delivery System: A Review and Outlook. Rev. Adv. Mater. Sci. 2019;58:82–97. doi: 10.1515/rams-2019-0010. DOI

Trucillo P. Drug Carriers: Classification, Administration, Release Profiles, and Industrial Approach. Processes. 2021;9:470. doi: 10.3390/pr9030470. DOI

Adeyemi O.S., Sulaiman F.A. Evaluation of metal nanoparticles for drug delivery systems. J. Biomed. Res. 2015;29:145–149. doi: 10.7555/JBR.28.20130096. PubMed DOI PMC

Kong F.Y., Zhang J.W., Li R.F., Wang Z.X., Wang W.J., Wang W. Unique roles of gold nanoparticles in drug delivery, targeting and imaging applications. Molecules. 2017;22:1445. doi: 10.3390/molecules22091445. PubMed DOI PMC

Singh P., Pandit S., Mokkapati V.R.S.S., Garg A., Ravikumar V., Mijakovic I. Gold nanoparticles in diagnostics and therapeutics for human cancer. Int. J. Mol. Sci. 2018;19:1979. doi: 10.3390/ijms19071979. PubMed DOI PMC

Jampilek J., Kralova K. Advances in drug delivery nanosystems using graphene-based materials and carbon nanotubes. Materials. 2021;14:1059. doi: 10.3390/ma14051059. PubMed DOI PMC

Tanaka M., Aoki K., Haniu H., Kamanaka T., Takizawa T., Sobajima A., Yoshida K., Okamoto M., Kato H., Saito N. Applications of carbon nanotubes in bone regenerative medicine. Nanomaterials. 2020;10:659. doi: 10.3390/nano10040659. PubMed DOI PMC

Anisimov R.A., Gorin D.A., Abalymov A.A. 3D Cell Spheroids as a Tool for Evaluating the Effectiveness of Carbon Nanotubes as a Drug Delivery and Photothermal Therapy Agents. C. 2022;8:56. doi: 10.3390/c8040056. DOI

Nair A., Haponiuk J.T., Thomas S., Gopi S. Natural carbon-based quantum dots and their applications in drug delivery: A review. Biomed. Pharmacother. 2020;132:110834. doi: 10.1016/j.biopha.2020.110834. PubMed DOI PMC

Iannazzo D., Pistone A., Celesti C., Triolo C., Patané S., Giofré S.V., Romeo R., Ziccarelli I., Mancuso R., Gabriele B., et al. A smart nanovector for cancer targeted drug delivery based on graphene quantum dots. Nanomaterials. 2019;9:282. doi: 10.3390/nano9020282. PubMed DOI PMC

Mousavi S.M., Hashemi S.A., Kalashgrani M.Y., Omidifar N., Bahrani S., Rao N.V., Babapoor A., Gholami A., Chiang W.H. Bioactive Graphene Quantum Dots Based Polymer Composite for Biomedical Applications. Polymers. 2022;14:617. doi: 10.3390/polym14030617. PubMed DOI PMC

Festas A.J., Ramos A., Davim J.P. Medical devices biomaterials—A review. Proc. Inst. Mech. Eng. Part L J. Mater. Des. Appl. 2020;234:218–228. doi: 10.1177/1464420719882458. DOI

Li H., Li C., Wu L., Wang H., Li J., Fu M., Wang C.A. In-situ synthesis and properties of porous cordierite ceramics with adjustable pore structure. Ceram. Int. 2020;46:14808–14815. doi: 10.1016/j.ceramint.2020.03.005. DOI

Gbureck U., Vorndran E., Barralet J.E. Modeling vancomycin release kinetics from microporous calcium phosphate ceramics comparing static and dynamic immersion conditions. Acta Biomater. 2008;4:1480–1486. doi: 10.1016/j.actbio.2008.02.027. PubMed DOI

Zamoume O., Thibault S., Regnié G., Mecherri M.O., Fiallo M., Sharrock P. Macroporous calcium phosphate ceramic implants for sustained drug delivery. Mater. Sci. Eng. C. 2011;31:1352–1356. doi: 10.1016/j.msec.2011.04.020. DOI

Vezenkova A., Locs J. Sudoku of porous, injectable calcium phosphate cements—Path to osteoinductivity. Bioact. Mater. 2022;17:109–124. doi: 10.1016/j.bioactmat.2022.01.001. PubMed DOI PMC

Mahjoory M., Shahgholi M., Karimipour A. The Effects of Initial Temperature and Pressure on the Mechanical Properties of Reinforced Calcium Phosphate Cement with Magnesium Nanoparticles; a Molecular Dynamics Approach. SSRN Electron. J. 2022;135:106067. doi: 10.2139/ssrn.4025902. DOI

Kołodziejska B., Kaflak A., Kolmas J. Biologically inspired collagen/apatite composite biomaterials for potential use in bone tissue regeneration—A review. Materials. 2020;13:1748. doi: 10.3390/ma13071748. PubMed DOI PMC

Motameni A., Alshemary A.Z., Evis Z. A review of synthesis methods, properties and use of monetite cements as filler for bone defects. Ceram. Int. 2021;47:13245–13256. doi: 10.1016/j.ceramint.2021.01.240. DOI

Braga R.R. Calcium phosphates as ion-releasing fillers in restorative resin-based materials. Dent. Mater. 2019;35:3–14. doi: 10.1016/j.dental.2018.08.288. PubMed DOI

Dorozhkin S.V. Calcium orthophosphates (CaPO4): Occurrence and properties. Prog. Biomater. 2015;5:9–70. doi: 10.1007/s40204-015-0045-z. PubMed DOI PMC

Matsuya S., Takagi S., Chow L.C. Effect of mixing ratio and pH on the reaction between Ca4(PO4)2O and CaHPO4. J. Mater. Sci. Mater. Med. 2000;1:305–311. doi: 10.1023/A:1008961314500. PubMed DOI

Ślósarczyk A. Bioceramika Hydroksyapatytowa. Biuletyn Ceramiczny nr 13 Ceramika 51; Polskie Towarzystwo Ceramiczne; Kraków, Poland: 1997.

Harb S.V., Bassous N.J., de Souza T.A.C., Trentin A., Pulcinelli S.H., Santilli C.V., Webster T.J., Lobo A.O., Hammer P. Hydroxyapatite and β-TCP modified PMMA-TiO2 and PMMA-ZrO2 coatings for bioactive corrosion protection of Ti6Al4V implants. Mater. Sci. Eng. C. 2020;116:111149. doi: 10.1016/j.msec.2020.111149. PubMed DOI

Damerau J.M., Bierbaum S., Wiedemeier D., Korn P., Smeets R., Jenny G., Nadalini J., Stadlinger B. A systematic review on the effect of inorganic surface coatings in large animal models and meta-analysis on tricalcium phosphate and hydroxyapatite on periimplant bone formation. J. Biomed. Mater. Res. Part B Appl. Biomater. 2022;110:157–175. doi: 10.1002/jbm.b.34899. PubMed DOI PMC

Shalini B., Kumar A.R. A comparative study of hydroxyapatite (Ca10(PO4)6(OH)2) using sol-gel and co-precipitation methods for biomedical applications. J. Indian Cham. Soc. 2019;96:25–28.

De Aza P.N., Rodríguez M.A., Gehrke S.A., Maté-Sánchez de Val J.E., Calvo-Guirado J.L. A Si-αTCP scaffold for biomedical applications: An experimental study using the rabbit tibia model. Appl. Sci. 2017;7:706. doi: 10.3390/app7070706. DOI

Horch H.H., Sader R., Pautke C., Neff A., Deppe H., Kolk A. Synthetic, pure-phase beta-tricalcium phosphate ceramic granules (Cerasorb®) for bone regeneration in the reconstructive surgery of the jaws. Int. J. Oral Maxillofac. Surg. 2006;35:708–713. doi: 10.1016/j.ijom.2006.03.017. PubMed DOI

Sánchez-Salcedo S., Arcos D., Vallet-Regí M. Upgrading Calcium Phosphate Scaffolds for Tissue Engineering Applications. Key Eng. Mater. 2008;377:19–42. doi: 10.4028/www.scientific.net/KEM.377.19. DOI

Mirkiani S., Mesgar A.S., Mohammadi Z., Matinfar M. Synergetic reinforcement of brushite cements by monetite/apatite whisker-like fibers and carboxymethylcellulose. Materialia. 2022;21:101329. doi: 10.1016/j.mtla.2022.101329. DOI

Hurle K., Maia F.R., Ribeiro V.P., Pina S., Oliveira J.M., Goetz-Neunhoeffer F., Reis R.L. Osteogenic lithium-doped brushite cements for bone regeneration. Bioact. Mater. 2022;16:403–417. doi: 10.1016/j.bioactmat.2021.12.025. PubMed DOI PMC

Ben-Nissan B. Advances in Calcium Phosphate Biomaterials. Springer; Berlin/Heidelberg, Germany: 2014.

Qadir M., Li Y., Wen C. Ion-substituted calcium phosphate coatings by physical vapor deposition magnetron sputtering for biomedical applications: A review. Acta Biomaterialia. 2019;89:14–32. doi: 10.1016/j.actbio.2019.03.006. PubMed DOI

Tavoni M., Dapporto M., Tampieri A., Sprio S. Bioactive calcium phosphate-based composites for bone regeneration. J. Compos. Sci. 2021;5:227. doi: 10.3390/jcs5090227. DOI

Jeong J., Kim J.H., Shim J.H., Hwang N.S., Heo C.Y. Bioactive calcium phosphate materials and applications in bone regeneration. Biomater. Res. 2019;23:4. doi: 10.1186/s40824-018-0149-3. PubMed DOI PMC

Frank O., Heim M., Jakob M., Barbero A., Schäfer D., Bendik I., Dick W., Heberer M., Martin I. Real-time quantitative RT-PCR analysis of human bone marrow stromal cells during osteogenic differentiation in vitro. J. Cell. Biochem. 2002;85:737–746. doi: 10.1002/jcb.10174. PubMed DOI

Whited B.M., Skrtic D., Love B.J., Goldstein A.S. Osteoblast response to zirconia-hybridized pyrophosphate-stabilized amorphous calcium phosphate. J. Biomed. Mater. Res. Part A. 2006;76A:596–604. doi: 10.1002/jbm.a.30573. PubMed DOI PMC

Orimo H. The mechanism of mineralization and the role of alkaline phosphatase in health and disease. Nippon Med. Sch. 2010;77:4–12. doi: 10.1272/jnms.77.4. PubMed DOI

Bystrova A.V., Dekhtyar Y.D., Popov A.I., Coutinho J., Bystrov V.S. Modified hydroxyapatite structure and properties: Modeling and synchrotron data analysis of modified hydroxyapatite structure. Ferroelectrics. 2015;475:135–147. doi: 10.1080/00150193.2015.995580. DOI

Hübner W., Blume A., Pushnjakova R., Dekhtyar Y., Hein H.J. The influence of X-ray radiation on the mineral/organic matrix interaction of bone tissue: An FT-IR microscopic investigation. Int. J. Artif. Organs. 2005;28:66–73. doi: 10.1177/039139880502800111. PubMed DOI

Moroi H., Kimura K., Ido A., Banno H., Jin W., Wachino J.I., Yamada K., Kikkawa F., Park Y.J., Arakawa Y. Erythromycin-susceptible but clindamycin-resistant phenotype of clinical ermb-pcr-positive group b streptococci isolates with is1216e-inserted ermb. Jpn. J. Infect. Dis. 2019;72:420–422. doi: 10.7883/yoken.JJID.2019.015. PubMed DOI

Hu H., Ramezanpour M., Hayes A.J., Liu S., Psaltis A.J., Wormald P.J., Vreugde S. Sub-inhibitory clindamycin and azithromycin reduce s. Aureus exoprotein induced toxicity, inflammation, barrier disruption and invasion. J. Clin. Med. 2019;8:1617. doi: 10.3390/jcm8101617. PubMed DOI PMC

Ahmadi H., Ebrahimi A., Ahmadi F. Antibiotic Therapy in Dentistry. Int. J. Dent. 2021;2021:1–10. doi: 10.1155/2021/6667624. PubMed DOI PMC

Álvarez L.A., Van de Sijpe G., Desmet S., Metsemakers W.J., Spriet I., Allegaert K., Rozenski J. Ways to Improve Insights into Clindamycin Pharmacology and Pharmacokinetics Tailored to Practice. Antibiotics. 2022;11:701. doi: 10.3390/antibiotics11050701. 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

Tomala A.M., Słota D., Florkiewicz W., Piętak K., Dyląg M., Sobczak-Kupiec A. Tribological Properties and Physiochemical Analysis of Polymer-Ceramic Composite Coatings for Bone Regeneration. Lubricants. 2022;10:58. doi: 10.3390/lubricants10040058. DOI

Sawada M., Sridhar K., Kanda Y., Yamanaka S. Pure hydroxyapatite synthesis originating from amorphous calcium carbonate. Sci. Rep. 2021;11:1–9. doi: 10.1038/s41598-021-91064-y. PubMed DOI PMC

Słota D., Florkiewicz W., Sobczak-Kupiec A. Ceramic-polymer coatings on Ti-6Al-4V alloy modified with L-cysteine in biomedical applications. Mater. Today Commun. 2020;25:101301. doi: 10.1016/j.mtcomm.2020.101301. DOI

Florkiewicz W., Słota D., Placek A., Pluta K., Tyliszczak B., Douglas T.E.L., Sobczak-Kupiec A. Synthesis and characterization of polymer-based coatings modified with bioactive ceramic and bovine serum albumin. J. Funct. Biomater. 2021;12:21. doi: 10.3390/jfb12020021. PubMed DOI PMC

Gong X., Liang Z., Yang Y., Liu H., Ji J., Fan Y. A resazurin-based, nondestructive assay for monitoring cell proliferation during a scaffold-based 3D culture process. Regen. Biomater. 2020;7:271–281. doi: 10.1093/rb/rbaa002. PubMed DOI PMC

European Committee on Antimicrobial Susceptibility Testing . Breakpoint Tables for Interpretation of MICs and Zone Diameters. European Committee on Antimicrobial Susceptibility Testing; Växjö, Sweden: 2013. Version 13.0.

Bilton M.W. Ph.D. Thesis. University of Leeds; Leeds, UK: 2012. Nanoparticulate Hydroxyapatite and Calcium—Based CO2 Sorbents; pp. 201–282.

Chang M.C. Use of Wet Chemical Method to Prepare β Tri-Calcium Phosphates having Macro- and Nano-crystallites for Artificial Bone. J. Korean Ceram. Soc. 2016;53:670–675. doi: 10.4191/kcers.2016.53.6.670. DOI

Nur A., Jumari A., Budiman A.W., Wicaksono A.H., Nurohmah A.R., Nazriati N., Fajaroh F. Synthesis of nickel—Hydroxyapatite by electrochemical method. IOP Conf. Ser. Mater. Sci. Eng. 2019;543:012026. doi: 10.1088/1757-899X/543/1/012026. 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;4:119–122. doi: 10.4236/jbnb.2013.42016. DOI

Mansour S.F., El-dek S.I., Ahmed M.A., Abd-Elwahab S.M., Ahmed M.K. Effect of preparation conditions on the nanostructure of hydroxyapatite and brushite phases. Appl. Nanosci. 2016;6:991–1000. doi: 10.1007/s13204-015-0509-4. DOI

Ding X., Li A., Yang F., Sun K., Sun X. Β-Tricalcium Phosphate and Octacalcium Phosphate Composite Bioceramic Material for Bone Tissue Engineering. J. Biomater. Appl. 2020;34:1294–1299. doi: 10.1177/0885328220903989. PubMed DOI

Duarte Moreira A.P., Soares Sader M., De Almeida Soares G.D., Leão M.H.M.R. Strontium incorporation on microspheres of alginate/β-tricalcium phosphate as delivery matrices. Mater. Res. 2014;17:967–973. doi: 10.1590/S1516-14392014005000095. DOI

Besleaga C., Nan B., Popa A.C., Balescu L.M., Nedelcu L., Neto A.S., Pasuk I., Leonat L., Popescu-Pelin G., Ferreira J.M.F., et al. Sr and Mg Doped Bi-Phasic Calcium Phosphate Macroporous Bone Graft Substitutes Fabricated by Robocasting: A Structural and Cytocompatibility Assessment. J. Funct. Biomater. 2022;13:123. doi: 10.3390/jfb13030123. PubMed DOI PMC

Rojas-Montoya I.D., Fosado-Esquivel P., Henao-Holguín L.V., Esperanza-Villegas A.E., Bernad-Bernad M.J., Gracia-Mora J. Adsorption/desorption studies of norfloxacin on brushite nanoparticles from reverse microemulsions. Adsorption. 2020;26:825–834. doi: 10.1007/s10450-019-00138-x. DOI

Sayahi M., Santos J., El-Feki H., Charvillat C., Bosc F., Karacan I., Milthorpe B., Drouet C. Brushite (Ca,M)HPO4, 2H2O doping with bioactive ions (M = Mg2+, Sr2+, Zn2+, Cu2+, and Ag+): A new path to functional biomaterials? Mater. Today Chem. 2020;16:100230. doi: 10.1016/j.mtchem.2019.100230. DOI

Idowu B., Cama G., Deb S., Di Silvio L. In vitro osteoinductive potential of porous monetite for bone tissue engineering. J. Tissue Eng. 2014;5:1–4. doi: 10.1177/2041731414536572. PubMed DOI PMC

Ma M.Y., Zhu Y.J., Li L., Cao S.W. Nanostructured porous hollow ellipsoidal capsules of hydroxyapatite and calcium silicate: Preparation and application in drug delivery. J. Mater. Chem. 2008;18:2722–2727. doi: 10.1039/b800389k. DOI

Zhao Q., Zhang D., Sun R., Shang S., Wang H., Yang Y., Wang L., Liu X., Sun T., Chen K. Adsorption behavior of drugs on hydroxyapatite with different morphologies: A combined experimental and molecular dynamics simulation study. Ceram. Int. 2019;45:19522–19527. doi: 10.1016/j.ceramint.2019.06.068. DOI

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