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Development of porous HAp and β-TCP scaffolds by starch consolidation with foaming method and drug-chitosan bilayered scaffold based drug delivery system

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Abstract

The inability to maintain high concentrations of antibiotic at the site of infection for an extended period of time along with dead space management is still the driving challenge in treatment of osteomyelitis. Porous bioactive ceramics such as hydroxyapatite (HAp) and beta-tri calcium phosphate (β-TCP) were some of the alternatives to be used as local drug delivery system. However, high porosity and high interconnectivity of pores in the scaffolds play a pivotal role in the drug release and bone resorption. Ceftriaxone is a cephalosporin that has lost its clinical popularity. But has recently been reported to exhibit better bactericidal activity in vitro and reduced probability of resistance development, in combination with sulbactam, a β-lactamase inhibitor. In this article, a novel approach of forming HAp and pure β-TCP based porous scaffolds by applying together starch consolidation with foaming method was used. For the purpose, pure HAp and β-TCP were prepared in the laboratory and after thorough characterization (including XRD, FTIR, particle size distribution, etc.) the powders were used for scaffold fabrication. The ability of these scaffolds to release drugs suitably for osteomyelitis was studied in vitro. The results of the study indicated that HAp exhibited better drug release profile than β-TCP when drug was used alone indicating the high influence of the carrier material. However, this restriction got relaxed when a bilayered scaffold was formed using chitosan along with the drug. SEM studies along with EDAX on the drug-chitosan bilayered scaffold showed closest apposition of this combination to the calcium phosphate surface.

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References

  1. Soundrapandian C, Datta S, Sa B. Drug-eluting implants for osteomyelitis. Crit Rev Ther Drug Carrier Syst. 2007;24(6):493–545.

    CAS  PubMed  Google Scholar 

  2. Soundrapandian C, Sa B, Datta S. Organic-inorganic composites for bone drug delivery. AAPS PharmSciTech. 2009;10(4):1158–71.

    Article  CAS  PubMed  Google Scholar 

  3. Chen L, Wang H, Wang J, Chen M, Shang L. Ofloxacin-delivery system of a polyanhydride and polylactide blend used in the treatment of bone infection. J Biomed Mater Res B Appl Biomater. 2007;83(2):589–95.

    PubMed  Google Scholar 

  4. Efstathopoulos N, Giamarellos-Bourboulis E, Kanellakopoulou K, Lazarettos I, Giannoudis P, Frangia K, et al. Treatment of experimental osteomyelitis by methicillin resistant staphylococcus aureus with bone cement system releasing grepafloxacin. Injury. 2008;39(12):1384–90.

    Article  PubMed  Google Scholar 

  5. Liu-Snyder P, Webster TJ. Developing a new generation of bone cements with nanotechnology. Curr Nanosci. 2008;4(1):111–8.

    Article  CAS  ADS  Google Scholar 

  6. Anagnostakos K, Hitzler P, Pape D, Kohn D, Kelm J. Persistence of bacterial growth on antibiotic-loaded beads: Is it actually a problem? Acta Orthop. 2008;79(2):302–7.

    Article  PubMed  Google Scholar 

  7. Nandi SK, Kundu B, Ghosh SK, De DK, Basu D. Efficacy of nano-hydroxyapatite prepared by an aqueous solution combustion technique in healing bone defects of goat. J Vet Sci. 2008;9(2):183–91.

    Article  PubMed  Google Scholar 

  8. Nandi SK, Ghosh SK, Kundu B, De DK, Basu D. Evaluation of new porous β-tri-calcium phosphate ceramic as bone substitute in goat model. Small Ruminant Res. 2008;75(2–3):144–53.

    Article  Google Scholar 

  9. Ghosh SK, Nandi SK, Kundu B, Datta S, De DK, Roy SK, et al. In vivo response of porous hydroxyapatite and beta-tricalcium phosphate prepared by aqueous solution combustion method and comparison with bioglass scaffolds. J Biomed Mater Res B Appl Biomater. 2008;86(1):217–27.

    PubMed  Google Scholar 

  10. Nandi SK, Kundu B, Ghosh SK, Mandal TK, Datta S, De DK, et al. Cefuroxime-impregnated calcium phosphates as an implantable delivery system in experimental osteomyelitis. Ceram Int. 2009;35(4):1367–76.

    Article  CAS  Google Scholar 

  11. Nandi SK, Mukherjee P, Roy S, Kundu B, De DK, Basu D. Local antibiotic delivery systems for the treatment of osteomyelitis–a review. Mater Sci Engg C. 2009;29(8):2478–85.

    Article  CAS  Google Scholar 

  12. Nandi SK, Kundu B, Mukherjee P, Mandal TK, Datta S, De DK, et al. In vitro and in vivo release of cefuroxime axetil from bioactive glass as an implantable delivery system in experimental osteomyelitis. Ceram Int. 2009;35(8):3207–16.

    Article  CAS  Google Scholar 

  13. Klawitter JJ, Hulbert SF. Application of porous ceramics for the attachment of load bearing internal orthopaedic application. J Biomed Mater Res Symposium No 2. 1971;Part 1:161-229.

    Google Scholar 

  14. de Groot K, Klein CPAT, Wolke JGC, de Blieck-Hogervorst JMA. Chemistry of calcium phosphate bioceramics. In: Yamamuro T, Hench LL, Wilson J, editors. Handbook of bioactive ceramics. Vol. 2: Calcium phosphate and hydroxylapatite ceramics. Boca Raton: CRC Press; 1990. p. 3–16.

    Google Scholar 

  15. White EW, Weber JN, Roy DM, Owen EL, Chiroff RT, White RA. Replamineform porous biomaterials for hard tissue implant applications. J Biomed Mater Res. 1975;9(4):23–7.

    Article  CAS  PubMed  Google Scholar 

  16. Hulbert SF, Morrison SJ, Klawitter JJ. Tissue reaction to three ceramics of porous and non-porous structures. J Biomed Mater Res. 1972;6(5):347–74.

    Article  CAS  PubMed  Google Scholar 

  17. Sopyan I, Mel M, Ramesh S, K.A. K. Porous hydroxyapatite for artificial bone applications. Sci Tech Adv Mater. 2007;8:116–23.

    Article  CAS  Google Scholar 

  18. Lyckfeldt O, Ferreira JMF. Processing of porous ceramics by ‘starch consolidation’. J Eur Ceram Soc. 1998;18(2):131–40.

    Article  CAS  Google Scholar 

  19. Rutenberg M. Starch and its modifications. Handbook of water-soluble gums and resins. New York: McGraw Hill; 1979.

    Google Scholar 

  20. Shrivastava SM, Saurabh S, Rai D, Dwivedi VK, Chaudhary M. In vitro microbial efficacy of sulbactomax: A novel fixed dose combination of ceftriaxone sulbactam and ceftriaxone alone. Curr Drug Ther. 2009;4(1):73–7.

    Article  CAS  Google Scholar 

  21. Zhao F, Grayson WL, Ma T, Bunnell B, Lu WW. Effects of hydroxyapatite in 3-d chitosan-gelatin polymer network on human mesenchymal stem cell construct development. Biomaterials. 2006;27(9):1859–67.

    Article  CAS  PubMed  Google Scholar 

  22. Zhang L, Ao Q, Wang A, Lu G, Kong L, Gong Y, et al. A sandwich tubular scaffold derived from chitosan for blood vessel tissue engineering. J Biomed Mater Res A. 2006;77(2):277–84.

    PubMed  Google Scholar 

  23. Ao Q, Wang A, Cao W, Zhang L, Kong L, He Q, et al. Manufacture of multimicrotubule chitosan nerve conduits with novel molds and characterization in vitro. J Biomed Mater Res A. 2006;77(1):11–8.

    PubMed  Google Scholar 

  24. Kong L, Gao Y, Cao W, Gong Y, Zhao N, Zhang X. Preparation and characterization of nano-hydroxyapatite/chitosan composite scaffolds. J Biomed Mater Res A. 2005;75(2):275–82.

    PubMed  Google Scholar 

  25. Kundu B, Sarkar R, Banerjee G, Panda C, Basu D, inventors; Central Glass and Ceramic Research Institute IFGL Bioceramics Limited, assignee. An improved process for the synthesis of pure beta-tri-calcium phosphate (β-tcp) useful for biomedical application (applied). India 2009.

  26. Kundu B, Sinha MK, Mitra MK, Basu D. Fabrication and characterization of porous hydroxyapatite ocular implant followed by an in vivo study in dogs. Bull Mater Sci. 2004;27(2):133–40.

    Article  CAS  Google Scholar 

  27. Rodriguez-Lorenzo LM, Vallet-Regi M, Ferreira JM. Colloidal processing of hydroxyapatite. Biomaterials. 2001;22(13):1847–52.

    Article  CAS  PubMed  Google Scholar 

  28. Lemos AF, Santos JD, Ferreira JMF. New method for the incorporation of soluble bioactive glasses to reinforce porous ha structures. Key Engg Mater. 2003;254–256:1033–6.

    Google Scholar 

  29. ASTM Standard C773-88. Standard test method for compressive (crushing) strength of fired whiteware materials. West Conshohocken, PA: ASTM International; 2006. doi:10.1520/C0773-88R06.

  30. Klug HP, Alexander LE. X-ray diffraction procedures: For polycrystalline and amorphous materials. 2 ed. ed. Weinheim: Wiley-VCH; 1974.

    Google Scholar 

  31. Cullity BD, Stock SR. Elements of x-ray diffraction. 2 ed. ed. New Jersey: Prentice Hall; 2001.

    Google Scholar 

  32. Landi E, Tampieri A, Celotti G, Sprio S. Densification behaviour and mechanisms of synthetic hydroxyapatites. J Eur Ceram Soc. 2000;20(14–15):2377–87.

    Article  CAS  Google Scholar 

  33. LeGeros RZ. Calcium phosphates in oral biology and medicine. Monogr Oral Sci. 1991;15:1–201.

    CAS  PubMed  Google Scholar 

  34. Silva CC, Pinheiro AG, Miranda MAR, Goes JC, Sombra ASB. Structural properties of hydroxyapatite obtained by mechanosynthesis. Solid State Sci. 2003;5(4):553–8.

    Article  CAS  ADS  Google Scholar 

  35. Mostafa NY. Characterization, thermal stability and sintering of hydroxyapatite powders prepared by different routes. Mater Chem Phys. 2005;94(2–3):333–41.

    Article  CAS  Google Scholar 

  36. Yoshimura M, Suda H, Okamoto K, Ioku K. Hydrothermal synthesis of biocompatible whiskers. J Mater Sci. 1994;29(13):3399–402.

    Article  CAS  ADS  Google Scholar 

  37. Nelson DG, Featherstone JD. Preparation, analysis, and characterization of carbonated apatites. Calcif Tissue Int. 1982;34(Suppl 2):S69–81.

    PubMed  Google Scholar 

  38. Kutty TRN. Assignments of some bands in the infrared spectrum of b-tricalcium phosphate. Ind J Chem. 1970;8(7):655–7.

    CAS  Google Scholar 

  39. Jinawath S, Polchai D, Yoshimura M. Low-temperature, hydrothermal transformation of aragonite to hydroxyapatite. Mater Sci Engg C. 2002;22(1):35–9.

    Article  Google Scholar 

  40. Rahaman MN. Ceramic processing and sintering. 2 ed. ed. New York: Marcel Dekker; 2003.

    Google Scholar 

  41. Lemos AF, Ferreira JMF. Combining foaming and starch consolidation methods to develop macroporous ha implants. Key Engg Mater. 2004;254–256:1041–4.

    Article  Google Scholar 

  42. Minnear WP. Processing of foamed ceramics. Ceramic transactions, forming science and technology for ceramics. Westemille, Ohio: The American Ceramic Society; 1992.

    Google Scholar 

  43. Gibson LJ, Ashby MF. Cellular solids: Structure and properties. 2 ed. ed. Cambridge: Cambridge University Press; 1997.

    Google Scholar 

  44. Kuhne JH, Bartl R, Frisch B, Hammer C, Jansson V, Zimmer M. Bone formation in coralline hydroxyapatite. Effects of pore size studied in rabbits. Acta Orthop Scand. 1994;65(3):246–52.

    Article  CAS  PubMed  Google Scholar 

  45. Eggli PS, Muller W, Schenk RK. Porous hydroxyapatite and tricalcium phosphate cylinders with two different pore size ranges implanted in the cancellous bone of rabbits. A comparative histomorphometric and histologic study of bony ingrowth and implant substitution. Clin Orthop Relat Res. 1988;232:127–38.

    CAS  PubMed  Google Scholar 

  46. Holmes R, Mooney V, Bucholz R, Tencer A. A coralline hydroxyapatite bone graft substitute. Preliminary report. Clin Orthop Relat Res. 1984;188:252–62.

    CAS  PubMed  Google Scholar 

  47. Zhang M, Tan T, Yuan H, Rui C. Insecticidal and fungicidal activities of chitosan and oligo-chitosan. J Bioactive Compat Polym. 2003;18(5):391–400.

    Article  CAS  Google Scholar 

  48. Bodhak S, Bose S, Bandyopadhyay A. Role of surface charge and wettability on early stage mineralization and bone cell-materials interactions of polarized hydroxyapatite. Acta Biomater. 2009;5(6):2178–88.

    Article  CAS  PubMed  Google Scholar 

  49. Lima EG, Mauck RL, Han SH, Park S, Ng KW, Ateshian GA, et al. Functional tissue engineering of chondral and osteochondral constructs. Biorheology. 2004;41(3–4):577–90.

    PubMed  Google Scholar 

  50. Schaefer D, Martin I, Shastri P, Padera RF, Langer R, Freed LE, et al. In vitro generation of osteochondral composites. Biomaterials. 2000;21(24):2599–606.

    Article  CAS  PubMed  Google Scholar 

  51. Mahoney MJ, Saltzman WM. Transplantation of brain cells assembled around a programmable synthetic microenvironment. Nat Biotechnol. 2001;19(10):934–9.

    Article  CAS  PubMed  Google Scholar 

  52. Palazzo B, Sidoti MC, Roveri N, Tampieri A, Sandri M, Bertolazzi L, et al. Controlled drug delivery from porous hydroxyapatite grafts: An experimental and theoretical approach. Mater Sci Engg C. 2005;25(2):207–13.

    Article  Google Scholar 

  53. Rissing JP. Antimicrobial therapy for chronic osteomyelitis in adults: Role of the quinolones. Clin Infect Dis. 1997;25(6):1327–33.

    Article  CAS  PubMed  Google Scholar 

  54. Bush K. Beta-lactamase inhibitors from laboratory to clinic. Clin Microbiol Rev. 1988;1(1):109–23.

    CAS  MathSciNet  PubMed  Google Scholar 

  55. Lebugle A, Rodrigues A, Bonnevialle P, Voigt JJ, Canal P, Rodriguez F. Study of implantable calcium phosphate systems for the slow release of methotrexate. Biomaterials. 2002;23(16):3517–22.

    Article  CAS  PubMed  Google Scholar 

  56. Burgos AE, Belchior JC, Sinisterra RD. Controlled release of rhodium (ii) carboxylates and their association complexes with cyclodextrins from hydroxyapatite matrix. Biomaterials. 2002;23(12):2519–26.

    Article  CAS  PubMed  Google Scholar 

  57. LeGeros RZ, Bautista C, LeGeros JP, Vijaraghavan TV, Retino M. Comparative properties of bioactive bone graft materials. Bioceramics. London: Pergamon Press; 1995.

    Google Scholar 

  58. Stigter M, Bezemer J, de Groot K, Layrolle P. Incorporation of different antibiotics into carbonated hydroxyapatite coatings on titanium implants, release and antibiotic efficacy. J Control Release. 2004;99(1):127–37.

    Article  CAS  PubMed  Google Scholar 

  59. Prabaharan M. Chitosan derivatives as promising materials for controlled drug delivery. J Biomater Appl. 2008;23(1):5–36.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors wish to express their sincere thanks to Department of Science and Technology, India and Fundação para a Ciência e a Tecnologia, Portugal for funding this work and the Director, CGCRI, India and CICECO, University of Aveiro, Portugal for their support. All the personnel related to the characterization of the materials are sincerely acknowledged.

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Kundu, B., Lemos, A., Soundrapandian, C. et al. Development of porous HAp and β-TCP scaffolds by starch consolidation with foaming method and drug-chitosan bilayered scaffold based drug delivery system. J Mater Sci: Mater Med 21, 2955–2969 (2010). https://doi.org/10.1007/s10856-010-4127-0

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