Calcium Phosphate Cement Composed of Hydroxyapatite Modified Silica and Polyeugenol as a Bone Filler Material

Tri Windarti(1*), Nor Basid Adiwibawa Prasetya(2), Ngadiwiyana Ngadiwiyana(3), Limpat Nulandaya(4)

(1) Department of Chemistry, Faculty of Science and Mathematics, Universitas Diponegoro, Jl. Prof. Soedharto SH, Tembalang, Semarang 50275, Indonesia
(2) Department of Chemistry, Faculty of Science and Mathematics, Universitas Diponegoro, Jl. Prof. Soedharto SH, Tembalang, Semarang 50275, Indonesia
(3) Department of Chemistry, Faculty of Science and Mathematics, Universitas Diponegoro, Jl. Prof. Soedharto SH, Tembalang, Semarang 50275, Indonesia
(4) Center for Progressive Materials-Technology and Innovation Park, University of Pavol Jozef Šafárik, 04001 Košice, Slovakia; Institute of Experimental Physics, Slovak Academy of Sciences, Watsonova 47, 04001 Košice, Slovakia
(*) Corresponding Author


A composite of hydroxyapatite modified silica (HASiO2) and 10% (w/w) polyeugenol (PE) was synthesized to produce a calcium phosphate cement with antibacterial activity. The compatibility of the composite (HASiO2_PE) with bone filler requirements was determined due to its crystal, surface, antibacterial, and cytocompatibility properties. The results showed that compositing HASiO2 and PE did not affect HA's chemical dan crystal properties. The presence of PE changed HASiO2 morphology to be coarser and denser than before composited. PE tends to agglomerate but does not affect the hydrophilicity of HASiO2. The presence of PE increased the surface area and total pore volume but lowered the average pore size. Different from pure PE, the composite of HASiO2_PE that contains of 10% PE has higher antibacterial activity toward Escherichia coli than Staphylococcus aureus. The composite is biocompatible because the cytotoxicity test toward pre-osteoblast cells resulted in an IC50 of 2092 μg/mL. Thus, due to its chemical, surface, antibacterial, and cytocompatibility properties, the HASiO2_PE composite can be recommended as a bone filler material.


antibacterial; bone; calcium phosphate cement; hydroxyapatite; polyeugenol

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[1] Flurin, L., Greenwood-Quaintance, K.E., and Patel, R., 2019, Microbiology of polymicrobial prosthetic joint infection, Diagn. Microbiol. Infect. Dis., 94 (3), 255–259.

[2] Tubb, C.C., Polkowksi, G.G., and Krause, B., 2020, Diagnosis and prevention of periprosthetic joint infections, J. Am. Acad. Orthop. Surg., 28 (8), e340–e348.

[3] Izakovicova, P., Borens, O., and Trampuz, A., 2019, Periprosthetic joint infection: Current concepts and outlook, EFORT Open Rev., 4 (7), 482–494.

[4] Lipsky, B.A., Weigelt, J.A., Gupta, V., Killian, A., and Peng, M.M., 2007, Skin, soft tissue, bone, and joint infections in hospitalized patients: Epidemiology and microbiological, clinical, and economic outcomes, Infect. Control Hosp. Epidemiol., 28 (11), 1290–1298.

[5] Maaloum, Y., Meybeck, A., Olive, D., Boussekey, N., Delannoy, P.Y., Chiche, A., Georges, H., Beltrand, E., Senneville, E., d’Escrivan, T., and Leroy, O., 2013, Clinical spectrum and outcome of critically ill patients suffering from prosthetic joint infections, Infection, 41 (2), 493–501.

[6] Ginebra, M.P., Espanol, M., Montufar, E.B., Perez, R.A., and Mestres, G., 2010, New processing approaches in calcium phosphate cements and their applications in regenerative medicine, Acta Biomater., 6 (8), 2863–2873.

[7] Akao, M., Aoki, H, and Kato, K., 1981, Mechanical properties of sintered hydroxyapatite for prosthetic applications, J. Mater. Sci., 16 (3), 809–812.

[8] Moheet, I.A., Luddin, N., Ab Rahman, I., Masudi, M., Kannan, T.P., and Nik Abd Ghani, N.R., 2018, Evaluation of mechanical properties and bond strength of nano-hydroxyapatite-silica added glass ionomer cement, Ceram. Int., 44 (8), 9899–9906.

[9] Villacampa, A.I., and Garcı́a-Ruiz, J.M., 2000, Synthesis of a new hydroxyapatite-silica composite material, J. Cryst. Growth, 211 (1), 111–115.

[10] Lei, C., Cao, Y., Hosseinpour, S., Gao, F., Liu, J., Fu, J., Staples, R., Ivanovski, S., and Xu, C., 2021, Hierarchical dual-porous hydroxyapatite doped dendritic mesoporous silica nanoparticles based scaffolds promote osteogenesis in vitro and in vivo, Nano Res., 14 (3), 770–777.

[11] Windarti, T., Widjijono, W., and Nuryono, N., 2021, Deposition of hydroxyapatite on silica made from rice husk ash to produce powder component of calcium phosphate cement, Indones. J. Chem., 21 (3), 588–597.

[12] Qiao, Y., Zhai, Z., Chen, L., and Liu, H., 2015, Cytocompatible 3D chitosan/hydroxyapatite composites endowed with antibacterial properties: toward a self-sterilized bone tissue engineering scaffold, Sci. Bull., 60 (13), 1193–1202.

[13] Yang, Y., Campbell Ritchie, N., and Everitt, N.M., 2021, Recombinant human collagen/chitosan-based soft hydrogels as biomaterials for soft tissue engineering, Mater. Sci. Eng., C, 121, 111846.

[14] Shu, X., Liao, J., Wang, L., Shi, Q., and Xie, X., 2020, Osteogenic, angiogenic, and antibacterial bioactive nano-hydroxyapatite co-synthesized using γ-polyglutamic acid and copper, ACS Biomater. Sci. Eng., 6 (4), 1920–1930.

[15] Li, Z., Zhou, P., Zhou, F., Zhao, Y., Ren, L., and Yuan, X., 2018, Antimicrobial eugenol-loaded electrospun membranes of poly(ε-caprolactone)/gelatin incorporated with REDV for vascular graft applications, Colloids Surf., B, 162, 335–344.

[16] Modjinou, T., Versace, D.L., Abbad-Andaloussi, S., Langlois, V., and Renard, E., 2017, Antibacterial and antioxidant photoinitiated epoxy co-networks of resorcinol and eugenol derivatives, Mater. Today Commun., 12, 19–28.

[17] Li, M., Yu, H., Xie, Y., Guo, Y., Cheng, Y., Qian, H., and Yao, W., 2021, Fabrication of eugenol loaded gelatin nanofibers by electrospinning technique as active packaging material, LWT, 139, 110800.

[18] Xu, H., Zhang, D., and Li, J., 2019, Antibacterial nanoparticles with universal adhesion function based on dopamine and eugenol, J. Bioresour. Bioprod., 4 (3), 177–182.

[19] Melendez-Rodriguez, B., Figueroa-Lopez, K.J., Bernardos, A., Martínez-Máñez, R., Cabedo, L., Torres-Giner, S., and Lagaron, J.M., 2019, Electrospun antimicrobial films of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) containing eugenol essential oil encapsulated in mesoporous silica nanoparticles, Nanomaterials, 9 (2), 227.

[20] Saltan, F., 2021, Preparation of poly(eugenol-co-methyl methacrylate)/polypropylene blend by creative route approach: Structural and thermal characterization, Iran. Polym. J., 30 (11), 1227–1236.

[21] Predoi, S.A., Ciobanu, C.S., Motelica-Heino, M., Chifiriuc, M.C., Badea, M.L., and Iconaru, S.L., 2021, Preparation of porous hydroxyapatite using cetyl trimethyl ammonium bromide as surfactant for the removal of lead ions from aquatic solutions, Polymers, 13 (10), 1617.

[22] Li, Y., Tjandra, W., and Tam, K.C., 2008, Synthesis and characterization of nanoporous hydroxyapatite using cationic surfactants as templates, Mater. Res. Bull., 43 (8-9), 2318–2326.

[23] Larsson, S., Stadelmann, V.A., Arnoldi, J., Behrens, M., Hess, B., Procter, P., Murphy, M., and Pioletti, D.P., 2012, Injectable calcium phosphate cement for augmentation around cancellous bone screws. In vivo biomechanical studies, J. Biomech., 45 (7), 1156–1160.

[24] Fahami, A., Beall, G.W., and Betancourt, T., 2016, Synthesis, bioactivity and zeta potential investigations of chlorine and fluorine substituted hydroxyapatite, Mater. Sci. Eng., C, 59, 78–85.

[25] Malakauskaite-Petruleviciene, M., Stankeviciute, Z., Niaura, G., Prichodko, A., and Kareiva, V., 2015, Synthesis and characterization of sol-gel derived calcium hydroxyapatite thin films spin-coated on silicon substrate, Ceram. Int., 41 (6), 7421–7428.

[26] da Silva Brum, I., de Carvalho, I.I., da Silva Pires, J.L., de Carvalho, M.A.A., dos Santos, L.B.F., and Elias, C.N., 2019, Nanosized hydroxyapatite and β-tricalcium phosphate composite: Physico-chemical, cytotoxicity, morphological properties and in vivo trial, Sci. Rep., 9 (1), 19602.

[27] Singh, G., Jolly, S.S., and Singh, R.P., 2020, Cerium substituted hydroxyapatite mesoporous nanorods: Synthesis and characterization for drug delivery applications, Mater. Today: Proc., 28, 1460–1466.

[28] Wilson, O.C., and Hull, J.R., 2008, Surface modification of nanophase hydroxyapatite with chitosan, Mater. Sci. Eng., C, 28, 434–437.

[29] Fuh, L.J., Huang, Y.J., Chen, W.C., and Lin, D.J., 2017, Preparation of micro-porous bioceramic containing silicon-substituted hydroxyapatite and beta-tricalcium phosphate, Mater. Sci. Eng., C, 75, 798–806.

[30] Hajimirzaee, S., Chansai, S., Hardacre, C., Banks, C.E., and Doyle, A.M., 2019, Effects of surfactant on morphology, chemical properties and catalytic activity of hydroxyapatite, J. Solid State Chem., 276, 345–351.

[31] Prasetya, N.B.A., Asiyah, A., Sarjono, P.R., Ngadiwiyana, N., and Ismiyarto, I., 2021, Synthesis of sulfonated poly-(eugenol divinylbenzene) nanosilver composite and its application as antibacterial compound of cotton fabric, J. Phys.: Conf. Ser., 1943, 012183.

[32] Baharum, Z., Akim, A.M., Taufiq-Yap, Y.H., Hamid, R.A., and Kasran, R., 2014, In vitro antioxidant and antiproliferative activities of methanolic plant part extracts of Theobroma cacao, Molecules, 19 (11), 18317–18331.

[33] Atjanasuppat, K., Wongkham, W., Meepowpan, P., Kittakoop, P., Sobhon, P., Bartlett, A., and Whitfield, P.J., 2009, In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants from Thailand, J. Ethnopharmacol., 123 (3), 475–482.

[34] Noor, M., Al Mamun, M.A., Atique Ullah, A.K.M., Matsuda, A., Kawamura, G., Hakim, M.A., Islam, M.F., and Matin, M.A., 2021, Physics of Ce3+ ↔ Ce4+ electronic transition in phytosynthesized CeO2/CePO4 nanocomposites and its antibacterial activities, J. Phys. Chem. Solids, 148, 109751.

[35] Liu, J.L., Zhang, B., Song, S.J., Ma, M., Si, S.Y., Wang, Y.H., Xu, B.X., Feng, K., Wu, J.G., and Guo, Y.C., 2014, Bovine collagen peptides compounds promote the proliferation and differentiation of MC3T3-E1 pre-osteoblasts, PLoS One, 9 (6), e99920.


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