Highly biocompatible behaviour and slow degradation of a LDH (layered double hydroxide)-coating on implants in the middle ear of rabbits

  • Franziska Duda
  • Marc Kieke
  • Florian Waltz
  • Maria E. Schweinefuß
  • Muhammad Badar
  • Peter Paul Müller
  • Karl-Heinz Esser
  • Thomas Lenarz
  • Peter Behrens
  • Nils Kristian Prenzler
Biocompatibility Studies
Part of the following topical collections:
  1. Biocompatibility Studies


Chronic inflammation can irreversibly damage components of the ossicular chain which may lead to sound conduction deafness. The replacement of impaired ossicles with prostheses does not reduce the risk of bacterial infections which may lead to loss of function of the implant and consequently to additional damage of the connected structures such as inner ear, meninges and brain. Therefore, implants that could do both, reconstruct the sound conduction and in addition provide antibacterial protection are of high interest for ear surgery. Layered double hydroxides (LDHs) are promising novel biomaterials that have previously been used as an antibiotic-releasing implant coating to curb bacterial infections in the middle ear. However, animal studies of LDHs are scarce and there exist only few additional data on the biocompatibility and hardly any on the biodegradation of these compounds. In this study, middle ear prostheses were coated with an LDH compound, using suspensions of nanoparticles of an LDH containing Mg and Al as well as carbonate ions. These coatings were characterized and implanted into the middle ear of healthy rabbits for 10 days. Analysis of the explanted prostheses showed only little signs of degradation. A stable health constitution was observed throughout the whole experiment in every animal. The results show that LDH-based implant coatings are biocompatible and dissolve only slowly in the middle ear. They, therefore, appear as promising materials for the construction of controlled drug delivery vehicles.


Layered Double Hydroxide Cholesteatoma Drug Release System Bulla Tympanica Coated Prosthesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We acknowledge the financial support of the project by the German Research Foundation (DFG) within the Collaborative Research Centre SFB 599 (subprojects D1 and DR1). This work also profited from collaboration in the Cluster of Excellence “Hearing4all”.


  1. 1.
    Madana J, Yolmo D, Kalaiarasi R, Gopalakrishnan S, Sujatha S. Microbiological profile with antibiotic sensitivity pattern of cholesteatomatous chronic suppurative otitis media among children. Int J Pediatr Otorhinolaryngol. 2011;75:1104–8.CrossRefGoogle Scholar
  2. 2.
    Osma U, Cureoglu S, Hosoglu S. The complications of chronic otitis media: report of 93 cases. J Laryngol Otol. 2000;114:97–100.CrossRefGoogle Scholar
  3. 3.
    Battaglia A, McGrew BM, Jackson CG. Reconstruction of the entire ossicular conduction mechanism. Laryngoscope. 2003;113:654–8.CrossRefGoogle Scholar
  4. 4.
    Hwang J, Chu C, Liu T. Changes in bacteriology of discharging ears. J Laryngol Otol. 2002;116:686–9.CrossRefGoogle Scholar
  5. 5.
    Lensing R, Bleich A, Smoczek A, Glage S, Ehlert N, Luessenhop T, et al. Efficacy of nanoporous silica coatings on middle ear prostheses as a delivery system for antibiotics: an animal study in rabbits. Acta Biomater Acta Materialia Inc. 2013;9:4815–25.CrossRefGoogle Scholar
  6. 6.
    Vogt JC, Brandes G, Krüger I, Behrens P, Nolte I, Lenarz T, et al. A comparison of different nanostructured biomaterials in subcutaneous tissue. J Mater Sci Mater Med. 2008;19:2629–36.CrossRefGoogle Scholar
  7. 7.
    Khan AI, O’Hare D. Intercalation chemistry of layered double hydroxides: recent developments and applications. J Mater Chem. 2002;12:3191–8.CrossRefGoogle Scholar
  8. 8.
    Zhang LH, Li F, Evans DG, Duan X. Cu–Zn–(Mn)–(Fe)–Al Layered double hydroxides and their mixed metal oxides: physicochemical and catalytic properties in wet hydrogen peroxide oxidation of phenol. Ind Eng Chem Res. 2010;49:5959–68.CrossRefGoogle Scholar
  9. 9.
    Evans D, Duan X. Preparation of layered double hydroxides and their applications as additives in polymers, as precursors to magnetic materials and in biology and medicine. Chem Commun. 2006;485–96. doi: 10.1039/B510313B.
  10. 10.
    Khan A, Lei L, Norquist A, O’Hare D. Intercalation and controlled release of pharmaceutically active compounds from a layered double hydroxide. Chem Commun. 2001;2342–3. doi: 10.1039/B106465G.
  11. 11.
    Ambrogi V, Fardella G, Grandolini G, Perioli L. Intercalation compounds of hydrotalcite-like anionic clays with antiinflammatory agents–I. Intercalation and in vitro release of ibuprofen. Int J Pharm. 2001;220:23–32.CrossRefGoogle Scholar
  12. 12.
    Frunza MS, Popa MI, Lisa G, Hritcu D, Lion MSI, Marcel Lone Pop A. New hybrid compounds containing intercalated ciprofloxacin into layered double hydroxides: synthesis and characterization. Rev Roum Chim. 2008;53:827–31.Google Scholar
  13. 13.
    Boclair J, Braterman P. Layered double hydroxide stability. 1. Relative stabilities of layered double hydroxides and their simple counterparts. Chem Mater. 1999;11:298–302.CrossRefGoogle Scholar
  14. 14.
    Dagnon KL, Ambadapadi S, Shaito A, Ogbomo SM, DeLeon V, Golden TD, et al. Poly(L-lactic acid) nanocomposites with layered double hydroxides functionalized with ibuprofen. J Appl Polym Sci. 2009;113:1905–15.CrossRefGoogle Scholar
  15. 15.
    Silion M, Hritcu D, Jaba IM, Tamba B, Ionescu D, Mungiu OC, et al. In vitro and in vivo behavior of ketoprofen intercalated into layered double hydroxides. J Mater Sci Mater Med. 2010;21:3009–18.CrossRefGoogle Scholar
  16. 16.
    Li A, Qin L, Wang W, Zhu R, Yu Y, Liu H, et al. The use of layered double hydroxides as DNA vaccine delivery vector for enhancement of anti-melanoma immune response. Biomaterials. 2011;32:469–77.CrossRefGoogle Scholar
  17. 17.
    Hesse D, Badar M, Bleich A, Smoczek A, Glage S, Kieke M, et al. Layered double hydroxides as efficient drug delivery system of ciprofloxacin in the middle ear: an animal study in rabbits. J Mater Sci Mater Med. 2013;24:129–36.CrossRefGoogle Scholar
  18. 18.
    Stieve M, Hedrich HJ, Battmer RD, Behrens P, Müller P, Lenarz T. Experimental middle ear surgery in rabbits: a new approach for reconstructing the ossicular chain. Lab Anim. 2009;43:198–204.CrossRefGoogle Scholar
  19. 19.
    Dissemond J, Witthoff M, Brauns TC, Haberer D, Goos M. pH values in chronic wounds. Evaluation during modern wound therapy. Der Hautarzt. 2003;54:959–65.CrossRefGoogle Scholar
  20. 20.
    Bartsch I, Willbold E, Rosenhahn B, Witte F. Non-invasive pH-determination adjacent to degradable biomaterials in vivo. Acta Biomater. 2014;10:34–9.CrossRefGoogle Scholar
  21. 21.
    Janning C, Willbold E, Vogt C, Nellesen J, Meyer-Lindenberg A, Windhagen H, et al. Magnesium hydroxide temporarily enhancing osteoblast activity and decreasing the osteoclast number in peri-implant bone remodelling. Acta Biomater. 2010;6:1861–8.CrossRefGoogle Scholar
  22. 22.
    Huang X, Brazel CS. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J Control Release. 2001;73:121–36.CrossRefGoogle Scholar
  23. 23.
    Chakraborti M, Jackson J, Plackett D, Gilchrist S, Burt H. The application of layered double hydroxide clay (LDH)-poly (lactide-co-glycolic acid)(PLGA) film composites for the controlled release of antibiotics. J Mater Sci Mater Med. 2012;23:1705–13.CrossRefGoogle Scholar
  24. 24.
    Panda HS, Srivastava R, Bahadur D. Stacking of lamellae in Mg/Al hydrotalcites: effect of metal ion concentrations on morphology. Mater Res Bull. 2008;43:1448–55.CrossRefGoogle Scholar
  25. 25.
    Vucelic M, Jones W, Moggridge G. Cation ordering in synthetic layered double hydroxides. Clays Clay Miner. 1997;45:803–13.CrossRefGoogle Scholar
  26. 26.
    Carlino S, Hudson M. Reaction of molten sebacic acid with a layered (Mg/Al) double hydroxide. J Mater Chem. 1994;4:99–104.CrossRefGoogle Scholar
  27. 27.
    Del Arco M, Cebadera E, Gutiérrez S, Martín C, Montero MJ, Rives V, et al. Mg, Al layered double hydroxides with intercalated indomethacin: synthesis, characterization, and pharmacological study. J Pharm Sci. 2004;93:1649–58.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Franziska Duda
    • 1
  • Marc Kieke
    • 2
  • Florian Waltz
    • 2
  • Maria E. Schweinefuß
    • 2
  • Muhammad Badar
    • 3
    • 4
  • Peter Paul Müller
    • 3
  • Karl-Heinz Esser
    • 5
  • Thomas Lenarz
    • 1
  • Peter Behrens
    • 2
  • Nils Kristian Prenzler
    • 1
  1. 1.Cluster of Excellence “Hearing4all“, ENT DepartmentHannover Medical SchoolHannoverGermany
  2. 2.Cluster of Excellence “Hearing4all“, Institute for Inorganic ChemistryLeibniz University of HannoverHannoverGermany
  3. 3.Helmholtz Centre for Infection ResearchBraunschweigGermany
  4. 4.Gomal Center of Biochemistry and Biotechnology (GCBB)Gomal UniversityDera Ismail KhanPakistan
  5. 5.Institute of ZoologyUniversity of Veterinary Medicine, Foundation, HannoverHannoverGermany

Personalised recommendations