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In vitro bioactivity, cytocompatibility, and antibiotic release profile of gentamicin sulfate-loaded borate bioactive glass/chitosan composites

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Abstract

Borate bioactive glass-based composites have been attracting interest recently as an osteoconductive carrier material for local antibiotic delivery. In the present study, composites composed of borate bioactive glass particles bonded with a chitosan matrix were prepared and evaluated in vitro as a carrier for gentamicin sulfate. The bioactivity, degradation, drug release profile, and compressive strength of the composite carrier system were studied as a function of immersion time in phosphate-buffered saline at 37 °C. The cytocompatibility of the gentamicin sulfate-loaded composite carrier was evaluated using assays of cell proliferation and alkaline phosphatase activity of osteogenic MC3T3-E1 cells. Sustained release of gentamicin sulfate occurred over ~28 days in PBS, while the bioactive glass converted continuously to hydroxyapatite. The compressive strength of the composite loaded with gentamicin sulfate decreased from the as-fabricated value of 24 ± 3 MPa to ~8 MPa after immersion for 14 days in PBS. Extracts of the soluble ionic products of the borate glass/chitosan composites enhanced the proliferation and alkaline phosphatase activity of MC3T3-E1 cells. These results indicate that the gentamicin sulfate-loaded composite composed of chitosan-bonded borate bioactive glass particles could be useful clinically as an osteoconductive carrier material for treating bone infection.

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References

  1. Xie ZP, Liu X, Huang WH, et al. Treatment of osteomyelitis and repair of bone defect by degradable bioactive borate. J Controlled Release. 2009;139:118–26.

    Article  CAS  Google Scholar 

  2. Bucholz HW, Heinet K, Foerster GW. Infected prostheses: the role of antibiotic cement. In: D’Ambrosia RD, Marier RL, editors. Orthopaedic infections. New Jersey: Slack Inc; 1989. p. 477–88.

    Google Scholar 

  3. Zhao L, Yan X, Yu C, et al. Mesoporous bioactive glasses for controlled drug release. Microporous Mesoporous Mater. 2008;109:210–5.

    Article  CAS  Google Scholar 

  4. Xue JM, Shi M. PLGA/Mesoporous silica hybrid structure for controlled drug release. J Controlled Release. 2004;98:209–17.

    Article  CAS  Google Scholar 

  5. Xia W, Chang J. Well-ordered mesoporous bioactive glasses (MBG): a promising bioactive drug delivery system. J Controlled Release. 2006;110:522–30.

    Article  CAS  Google Scholar 

  6. Jain AK, Panchagnula R. Skeletal drug delivery systems. Int J Pharm. 2000;206:1–12.

    Article  CAS  Google Scholar 

  7. Lee CH, Singla A, Lee Y. Biomedical applications of collagen. Int J Pharm. 2001;221:1–22.

    Article  CAS  Google Scholar 

  8. Saito K, Hoshino T. Apatite-coated solid composition. US Patent 6344209, 2002.

  9. Liu X, Xie ZP, Huang WH, et al. Bioactive borate glass scaffolds: in vitro and in vivo evaluation for use as a drug delivery system in the treatment of bone infection. J Mater Sci Mater Med. 2010;21:575–82.

    Article  CAS  Google Scholar 

  10. Zhang X, Jia WJ, Huang WH, et al. Teicoplanin-loaded borate bioactive glass implants for treating chronic bone infection in a rabbit tibia osteomyelitis model. Biomaterials. 2010;31(22):5865–74.

    Article  CAS  Google Scholar 

  11. Rahaman MN, Day DE, Fu Q, et al. Bioactive glass in tissue engineering. Acta Biomater. 2011;7:2355–73.

    Article  CAS  Google Scholar 

  12. Fu Q, Saiz E, Rahaman MN, et al. Bioactive glass scaffolds for bone tissue engineering: state of the art and future perspectives. Mater Sci Eng C. 2011;31:1245–56.

    Article  CAS  Google Scholar 

  13. Rahaman MN, Brown RF, Day DE, et al. Bioactive glasses for non-bearing applications in total joint replacement. Semin Arthroplasty. 2007;17:102–12.

    Article  Google Scholar 

  14. Liang W, Rahaman MN, Day DE, et al. Bioactive borate glass scaffold for bone tissue engineering. J Non-Cryst Solids. 2008;354:1690–6.

    Article  CAS  Google Scholar 

  15. Huang TS, Rahaman MN, Day ED, et al. Porous and strong bioactive glass (13–93) scaffolds fabricated by freeze extrusion technique. Mater Sci Eng C. 2011;31:1482–9.

    Article  CAS  Google Scholar 

  16. Domingues ZR, Cortés ME, Gomes TA, et al. Bioactive glass as a drug delivery system of tetracycline and tetracycline associated with β-cyclodextrin. Biomaterials. 2004;25:327–33.

    Article  CAS  Google Scholar 

  17. Jia WT, Zhang X, Huang WH, et al. Novel borate glass chitosan composite as a delivery vehicle for teicoplanin in the treatment of chronic osteomyelitis. Acta Biomater. 2010;6:812–9.

    Article  CAS  Google Scholar 

  18. Yao AH, Wang D, Huang WH, et al. In vitro bioactive characteristics of borate-based glasses with controllable degradation behavior. J Am Ceram Soc. 2007;90(1):303–6.

    Article  CAS  Google Scholar 

  19. Liu X, Huang WH, Fu HL, et al. Bioactive borosilicate glass scaffolds: in vitro degradation and bioactivity behaviors. J Mater Sci Mater Med. 2009;20:1237–43.

    Article  CAS  Google Scholar 

  20. Brown RF, Day DE, Rahaman MN, et al. Growth and differentiation of osteoblastic cells on 13–93 bioactive glass fibers and scaffolds. Acta Biomater. 2008;4:387–96.

    Article  CAS  Google Scholar 

  21. Huang WH, Rahaman MN, Day DE, et al. Mechanisms for converting bioactive silicate, borate, and borosilicate glasses to hydroxyapatite in dilute phosphate solutions. Phys Chem Glasses. 2006;47(6):647–58.

    CAS  Google Scholar 

  22. Huang WH, Day DE, Rahaman MN, et al. Kinetics and mechanisms of the conversion of silicate (45S5), borate, and borosilicate glasses to hydroxyapatite in dilute phosphate solutions. J Mater Sci Mater Med. 2006;17:583–96.

    Article  CAS  Google Scholar 

  23. Fu Q, Rahaman MN, Fu HL, et al. Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. I. Preparation and in vitro degradation. J Biomed Mater Res Part A. 2011;95(1):164–71.

    Google Scholar 

  24. Fu Q, Rahaman MN, Bal BS, et al. Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. II. In vitro and in vivo biological evaluation. J Biomed Mater Res Part A. 2011;95(1):172–9.

    Google Scholar 

  25. Majeti NV, Ravi K. A review of chitin and chitosan applications. React Funct Polym. 2000;46:1–27.

    Article  Google Scholar 

  26. Frutos P, Diez-Peña E, Frutos G, et al. Release of gentamicin sulphate from a modified commercial bone cement. Effect of (2-hydroxyethyl methacrylate) comonomer and poly(N-vinyl-2-pyrrolidone) additive on release mechanism and kinetics. Biomaterials. 2002;23:3787–97.

    Article  CAS  Google Scholar 

  27. Clarot I, Chaimbault P, Hasdenteufel F, et al. Determination of gentamicin sulfate and related compounds by high-performance liquid chromatography with evaporative light scattering detection. J Chromatogr A. 2004;1031:281–7.

    Article  CAS  Google Scholar 

  28. Lowy FD. Staphylococcus aureus infections. N Engl J Med. 1998;339:520–32.

    Article  CAS  Google Scholar 

  29. Boyle VJ, Fancher ME. Ross Jr R W. Rapid, modified Kirby-Bauer susceptibility test with single, high-concentration antimicrobial disks. Antimicrob Agents Chemother. 1973;3:418–24.

    Article  CAS  Google Scholar 

  30. Ning J, Wang DP, Huang WH, et al. Preparation of borosilicate glass and their bioactivity and biodegradation in vitro. J Chin Ceram Soc. 2006;34(11):1326–30.

    CAS  Google Scholar 

  31. Zhang X, Fu HL, Huang WH, et al. In vitro bioactivity and cytocompatibility of porous scaffolds of bioactive borosilicate glasses. Chin Sci Bull. 2009;54(24):463–8.

    Google Scholar 

  32. Maeda H, Ishida EH, Kasuga T. Hydrothermal preparation of tobermorite incorporating phosphate species. Mater Lett. 2012;68:382–4.

    Article  CAS  Google Scholar 

  33. Kokubo T, Kim HM, Kawashita M. Novel bioactive materials with different mechanical properties. Biomaterials. 2003;24:2161–75.

    Article  CAS  Google Scholar 

  34. Goldstein SA. The mechanical properties of trabecular bone: dependence on anatomic location and function. J Biomech. 1987;20:1055–61.

    Article  CAS  Google Scholar 

  35. Doadrio JC, Arcos D, Vallet-Regí M, et al. Calcium sulphate-based cements containing cephalexin. Biomaterials. 2004;25:2629–35.

    Article  CAS  Google Scholar 

  36. Phaechamud T, Charoenteeraboon J. Antibacterial activity and drug release of chitosan sponge containing doxycycline hyclate. AAPS Pharm Sci Tech. 2008;9:829–35.

    Article  CAS  Google Scholar 

  37. Zhang Y, Zhang M. Calcium phosphate/chitosan composite scaffolds for controlled in vitro antibiotic drug release. J Biomed Mater Res. 2002;62:378–86.

    Article  CAS  Google Scholar 

  38. Hunt CD. One possible role of dietary boron in higher animals and humans. Biol Trace Elem Res. 1998;66:205–25.

    Article  CAS  Google Scholar 

  39. Ying X, Cheng S, Peng L, et al. Effect of boron on osteogenic differentiation of human bone marrow stromal cells. Biol Trace Elem Res. 2011;144:306–15.

    Article  CAS  Google Scholar 

  40. Devirian TA, Volpe SL. The physiological effects of dietary boron. Crit Rev Food Sci Nutr. 2003;43(2):219–31.

    Article  CAS  Google Scholar 

  41. Brown RF, Rahaman MN, Huang WH, et al. Effect of to borate glass composition on its conversion hydroxyapatite and on the proliferation of MC3T3-E1 cells. J Biomed Mater Res Part A. 2008;88:392–400.

    Google Scholar 

  42. Benderdour M, Bui-Van T, Dicko A, et al. In vivo and vitro effects of boron and boronated compounds. J Trace Elem Med Biol. 1998;12(1):2–7.

    Article  CAS  Google Scholar 

  43. Murray FJ. A human health risk assessment of boron (boric acid and borax) in drinking water, biochemical and physiologic consequences of boron deprivation in humans. Regul Toxicol Pharmacol. 1995;22:221–30.

    Article  CAS  Google Scholar 

  44. Forrest HN. Boron in human and animal nutrition. Plant Soil. 1997;193:199–208.

    Article  Google Scholar 

  45. Murray FJ. A comparative review of the pharmacokinetics of boric acid in rodents and humans. Biol Trace Elem Res. 1998;66:331–9.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China through the Projects 51072133, 81000788, 81201377 and by the Shanghai Science Committee through the project 12JC1408500.

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Authors and Affiliations

  1. Institute of Bioengineering and Information Technology Materials, Tongji University, Shanghai, 200092, China

    Xu Cui, Yifei Gu, Le Li, Hui Wang, Nai Zhou & Wenhai Huang

  2. Department of Orthopaedic Surgery, Shanghai Sixth People’s Hospital, Jiaotong University, Shanghai, 200233, China

    Zhongping Xie & Shihua Luo

  3. Department of Materials Science and Engineering, Center for Bone and Tissue Repair and Regeneration, Missouri University of Science and Technology, Rolla, MO, 65409, USA

    Mohamed N. Rahaman

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  1. Xu Cui
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Correspondence to Wenhai Huang.

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Cui, X., Gu, Y., Li, L. et al. In vitro bioactivity, cytocompatibility, and antibiotic release profile of gentamicin sulfate-loaded borate bioactive glass/chitosan composites. J Mater Sci: Mater Med 24, 2391–2403 (2013). https://doi.org/10.1007/s10856-013-4996-0

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