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Evaluation of three-dimensional silver-doped borate bioactive glass scaffolds for bone repair: Biodegradability, biocompatibility, and antibacterial activity

  • Hui Wang (a1), Shichang Zhao (a2), Xu Cui (a3), Yangyi Pan (a3), Wenhai Huang (a3), Song Ye (a3), Shihua Luo (a4), Mohamed N. Rahaman (a5), Changqing Zhang (a6) and Deping Wang (a7)...

The development of synthetic scaffolds with a desirable combination of properties, such as bioactivity, the ability to locally deliver antibacterial agents and high osteogenic capacity, is a challenging but promising approach in bone tissue engineering. In this study, scaffolds of a borosilicate bioactive glass (composition: 6Na2O, 8K2O, 8MgO, 22CaO, 36B2O3, 18SiO2, 2P2O5; mol%) with controllable antibacterial activity were developed by doping the parent glass with varying amounts of Ag2O (0.05, 0.5, and 1.0 wt%). The addition of the Ag2O lowered the compressive strength and degradation of the bioactive glass scaffolds but it did not affect the formation of hydroxyapatite on the surface of the glass as determined by energy dispersive x-ray analysis, x-ray diffraction, and Fourier transform infrared analysis. The Ag2O-doped scaffolds showed a sustained release of Ag ions over more than 8 weeks in simulated body fluid and resistance against colonization by the bacterial strains Escherichia coli and Staphylococcus aureus. In vitro cell culture showed better adhesion, proliferation, and alkaline phosphatase activity of murine osteoblastic MC3T3-E1 cells on the Ag2O-doped bioactive glass scaffolds than on the undoped scaffolds. The results indicate that these Ag-doped borosilicate bioactive glass scaffolds may have potential in repairing bone coupled with providing a lower risk of bacterial infection.

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1. Yang F., Wang J., Hou J., Guo H., and Liu C.S.: Bone regeneration using cell-mediated responsive degradable PEG-based scaffolds incorporating with rhBMP-2. Biomaterials 34(5), 1514 (2013).
2. Pauksch L., Hartmann S., Rohnke M., Szalay G., Alt V., Schnettler R., and Lips K.S.: Biocompatibility of silver nanoparticles and silver ions in primary human mesenchymal stem cells and osteoblasts. Acta Biomater. 10(1), 439 (2014).
3. Renaud A., Lavigne M., and Vendittoli P-A.: Periprosthetic joint infections at a teaching hospital in 1990–2007. Can. J. Surg. 55(6), 394 (2012).
4. Henslee A.M., Spicer P.P., Yoon D.M., Nair M.B., Meretoja V.V., Witherel K.E., Jansen J.A., Mikos A.G., and Kasper F.K.: Biodegradable composite scaffolds incorporating an intramedullary rod and delivering bone morphogenetic protein-2 for stabilization and bone regeneration in segmental long bone defects. Acta Biomater. 7(10), 3627 (2011).
5. Ye J.H., Xu Y.J., Gao J., Yan S.G., Zhao J., Tu Q.S., Zhang J., Duan X.J., Sommer C.A., Mostoslavsky G., Kaplan D.L., Wu Y.N., Zhang C.P., Wang L., and Chen J.: Critical-size calvarial bone defects healing in a mouse model with silk scaffolds and SATB2-modified iPSCs. Biomaterials 32(22), 5065 (2011).
6. Cao W. and Hench L.L.: Bioactive materials. Ceram. Int. 22(6), 493 (1996).
7. Tsigkou O., Jones J.R., Polak J.M., and Stevens M.M.: Differentiation of fetal osteoblasts and formation of mineralized bone nodules by 45S5 Bioglass® conditioned medium in the absence of osteogenic supplements. Biomaterials 30(21), 3542 (2009).
8. Sun J., Wei L., Liu X., Li J., Li B., Wang G., and Meng F.: Influences of ionic dissolution products of dicalcium silicate coating on osteoblastic proliferation, differentiation and gene expression. Acta Biomater. 5(4), 1284 (2009).
9. Liang W., Rahaman M.N., Day D.E., Marion N.W., Riley G.C., and Mao J.J.: Bioactive borate glass scaffold for bone tissue engineering. J. Non-Cryst. Solids 354(15), 1690 (2008).
10. Zhang X., Jia W., Gu Y., Xiao W., Liu X., Wang D., Zhang C., Huang W., Rahaman M.N., and Day D.E.: Teicoplanin-loaded borate bioactive glass implants for treating chronic bone infection in a rabbit tibia osteomyelitis model. Biomaterials 31(22), 5865 (2010).
11. Han X. and Day D.E.: Reaction of sodium calcium borate glasses to form hydroxyapatite. J. Mater. Sci.: Mater. Med. 18(9), 1837 (2007).
12. Huang W., Day D.E., Kittiratanapiboon K., and Rahaman M.N.: Kinetics and mechanisms of the conversion of silicate (45S5), borate, and borosilicate glasses to hydroxyapatite in dilute phosphate solutions. J. Mater. Sci.: Mater. Med. 17(7), 583 (2006).
13. Nielsen F.H.: The emergence of boron as nutritionally important throughout the life cycle. Nutrition 16(7), 512 (2000).
14. Durand L.A.H., Gongora A., Lopez J.M.P., Boccaccini A.R., Zago M.P., Baldi A., and Gorustovich A.: In vitro endothelial cell response to ionic dissolution products from boron-doped bioactive glass in the SiO2-CaO-P2O5-Na2O system. J. Mater. Chem. B 2(43), 7620 (2014).
15. Forrer R., Wenker C., Gautschi K., and Lutz H.: Concentration of 17 trace elements in serum and whole blood of plains viscachas (Lagostomus maximus) by ICP-MS, their reference ranges, and their relation to cataract. Biol. Trace Elem. Res. 81(1), 47 (2001).
16. Forrer R., Gautschi K., and Lutz H.: Simultaneous measurement of the trace elements Al, As, B, Be, Cd, Co, Cu, Fe, Li, Mn, Mo, Ni, Rb, Se, Sr, and Zn in human serum and their reference ranges by ICP-MS. Biol. Trace Elem. Res. 80(1), 77 (2001).
17. Bi L., Jung S., Day D., Neidig K., Dusevich V., Eick D., and Bonewald L.: Evaluation of bone regeneration, angiogenesis, and hydroxyapatite conversion in critical‐sized rat calvarial defects implanted with bioactive glass scaffolds. J. Biomed. Mater. Res., Part A 100(12), 3267 (2012).
18. Gristina A.G., Naylor P.T., and Myrvik Q.N.: Biomaterial-centered infections: Microbial adhesion versus tissue integration. In Pathogenesis of Wound and Biomaterial-Associated Infections, (Springer, London, UK, 1990); p. 193.
19. Choi O., Deng K.K., Kim N-J., Ross L. Jr., Surampalli R.Y., and Hu Z.: The inhibitory effects of silver nanoparticles, silver ions, and silver chloride colloids on microbial growth. Water Res. 42(12), 3066 (2008).
20. Kalishwaralal K., BarathManiKanth S., Pandian S.R.K., Deepak V., and Gurunathan S.: Silver nanoparticles impede the biofilm formation by Pseudomonas aeruginosa and Staphylococcus epidermidis . Colloids Surf., B 79(2), 340 (2010).
21. Moojen D.J.F., Spijkers S.N., Schot C.S., Nijhof M.W., Vogely H.C., Fleer A., Verbout A.J., Castelein R.M., Dhert W.J., and Schouls L.M.: Identification of orthopaedic infections using broad-range polymerase chain reaction and reverse line blot hybridization. J. Bone Jt. Surg. 89(6), 1298 (2007).
22. Harris L., Tosatti S., Wieland M., Textor M., and Richards R.: Staphylococcus aureus adhesion to titanium oxide surfaces coated with non-functionalized and peptide-functionalized poly (l-lysine)-grafted-poly (ethylene glycol) copolymers. Biomaterials 25(18), 4135 (2004).
23. Clement J.L. and Jarrett P.S.: Antibacterial silver. Met.-Based Drugs 1(5–6), 467 (1994).
24. Percival S., Bowler P., and Russell D.: Bacterial resistance to silver in wound care. J. Hosp. Infect. 60(1), 1 (2005).
25. Liu X., Huang W., Fu H., Yao A., Wang D., Pan H., and Lu W.W.: Bioactive borosilicate glass scaffolds: Improvement on the strength of glass-based scaffolds for tissue engineering. J. Mater. Sci.: Mater. Med. 20(1), 365 (2009).
26. Kokubo T. and Takadama H.: How useful is SBF in predicting in vivo bone bioactivity? Biomaterials 27(15), 2907 (2006).
27. King G.N., King N., and Hughes F.J.: Effect of two delivery systems for recombinant human bone morphogenetic protein-2 on periodontal regeneration in vivo. J. Periodontal Res. 33(3), 226 (1998).
28. Zheng F., Wang S., Wen S., Shen M., Zhu M., and Shi X.: Characterization and antibacterial activity of amoxicillin-loaded electrospun nano-hydroxyapatite/poly (lactic-co-glycolic acid) composite nanofibers. Biomaterials 34(4), 1402 (2013).
29. Erol M., Mouriňo V., Newby P., Chatzistavrou X., Roether J., Hupa L., and Boccaccini A.R.: Copper-releasing, boron-containing bioactive glass-based scaffolds coated with alginate for bone tissue engineering. Acta Biomater. 8(2), 792 (2012).
30. Boronin A., Koscheev S., and Zhidomirov G.: XPS and UPS study of oxygen states on silver. J. Electron Spectrosc. Relat. Phenom. 96(1–3), 43 (1998).
31. Liu X., Rahaman M.N., and Day D.E.: Conversion of melt-derived microfibrous borate (13-93B3) and silicate (45S5) bioactive glass in a simulated body fluid. J. Mater. Sci.: Mater. Med. 24(3), 583 (2013).
32. Jones J.R. and Hench L.L.: Factors affecting the structure and properties of bioactive foam scaffolds for tissue engineering. J. Biomed. Mater. Res., Part B 68(1), 36 (2004).
33. Ma Z., Kotaki M., Inai R., and Ramakrishna S.: Potential of nanofiber matrix as tissue-engineering scaffolds. Tissue Eng. 11(1–2), 101 (2005).
34. Baer C., Foldbjerg R., Hayashi Y., Sutherlans D.S., and Autrup H.: Toxicity of silver nanoparticles—Nanoparticle or silver ion? Toxicol. Lett. 208, 286 (2012).
35. Kittler S., Greulich C., Diendorf J., Koller M., and Epple M.: Toxicity of silver nanoparticles increases during storage because of dissolution of slow dissolution under release of silver ions. Chem. Mater. 22, 4548 (2010).
36. Park M.V., Neigh A.M., Vermeulen J.P., de la Fonteyne L.J., Verharen H.W., Briedé J.J., and van Loveren H. and de Jong W.H.: The effect of particle size on the cytotoxicity, inflammation, developmental toxicity and genotoxicity of silver nanoparticles. Biomaterials 32(36), 9810 (2011).
37. AshaRani P., Low Kah Mun G., Hande M.P., and Valiyaveettil S.: Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano 3(2), 279 (2008).
38. Rai M., Yadav A., and Gade A.: Silver nanoparticles as a new generation of antimicrobials. Biotechnol. Adv. 27(1), 76 (2009).
39. Albers C.E., Hofstetter W., Siebenrock K.A., Landmann R., and Klenke F.M.: In vitro cytotoxicity of silver nanoparticles on osteoblasts and osteoclasts at antibacterial concentrations. Nanotoxicology 7(1), 30 (2013).
40. Ewald A., Hösel D., Patel S., Grover L.M., Barralet J.E., and Gbureck U.: Silver-doped calcium phosphate cements with antimicrobial activity. Acta Biomater. 7(11), 4064 (2011).
41. Hunt C.D.: Dietary boron: Progress in establishing essential roles in human physiology. J. Trace Elem. Med. Biol. 26(2), 157 (2012).
42. Park M., Li Q., Shcheynikov N., Zeng W., and Muallem S.: NaBC1 is a ubiquitous electrogenic Na+-coupled borate transporter essential for cellular boron homeostasis and cell growth and proliferation. Mol. Cell 16(3), 331 (2004).
43. Gorustovich A.A., López J.M.P., Guglielmotti M.B., and Cabrini R.L.: Biological performance of boron-modified bioactive glass particles implanted in rat tibia bone marrow. Biomed. Mater. 1(3), 100 (2006).
44. Reddy K.M., Feris K., Bell J., Wingett D.G., Hanley C., and Punnoose A.: Selective toxicity of zinc oxide nanoparticles to prokaryotic and eukaryotic systems. Appl. Phys. Lett. 90(21), 213902 (2007).
45. Kohanski M.A., Dwyer D.J., and Collins J.J.: How antibiotics kill bacteria: From targets to networks. Nat. Rev. Microbiol. 8(6), 423 (2010).
46. Brogden K.A.: Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol. 3(3), 238 (2005).
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