Biomedical Microdevices

, Volume 11, Issue 4, pp 783–793 | Cite as

Novel biological/biohybrid prostheses for the ossicular chain: fabrication feasibility and preliminary functional characterization

  • Serena Danti
  • Cesare Stefanini
  • Delfo D’Alessandro
  • Stefania Moscato
  • Andrea Pietrabissa
  • Mario Petrini
  • Stefano Berrettini


Alternatives for ossicular replacements were fabricated in order to overcome persisting rejections in middle ear prosthetization. Unlike the synthetic prostheses in fashion, we propose biological and biohybrid replacements containing extra cellular matrix (ECM) molecules to improve biointegration. In this study, ECM-containing devices shaped as Partial Ossicular Replacement Prostheses (PORPs) were fabricated reproducing the current synthetic models. Biological PORPs were obtained from human decellularized cortical bone allografts by computer numerically controlled ultraprecision micromilling. Moreover, porous PORP-like scaffolds were produced and cultured with osteoinduced human mesenchymal stromal cells to generate in vitro bone ECM within the scaffold porosity (biohybrid PORPs). The acoustic responses of such devices were investigated and compared to those of commercial prostheses. Results showed that biological PORPs transmit mechanical signals with appropriate frequencies, amplitudes, and with early extinction time. Although signal transmission in biohybrid PORPs showed insufficient amplitude, we believe that tissue engineered constructs represent the new challenge in ossiculoplasty.


Partial Ossicular Replacement Prosthesis (PORP) Middle ear Bone graft Tissue engineering Mesenchymal Stem Cell (MSC) Acoustic features 



Regione Toscana (Italy) and Center for Excellence ENDOCAS (University of Pisa) (MIUR D.M. 17 Oct 2003, 193/2003) are gratefully acknowledged for funding this study. The authors wish to thank Dr. Antonios G. Mikos (Rice University, Houston, TX) and his research team for the technical support in scaffold fabrication and analysis. Many thanks are also due to Mr. Nicodemo Funaro (CRIM Lab, Scuola Superiore Sant’Anna, Pisa, Italy) for his fundamental contribution in allograft PORP fabrication. Paper number 003 of CUCCS-RRMR.


  1. J. Bergman. Arch. Otolaryngol. 97, 70 (1973)Google Scholar
  2. P. Bruschini, S. Berrettini, G. Segnini, S. Sellari Franceschini, S. Bocci, F. Piragine, M. Grosjacques. Acta Otorhinolaryngol. Ital. 11, 159 (1991)Google Scholar
  3. R.A. Chole, Otolaryngol. Clin. North Am. 27, 717 (1994)Google Scholar
  4. S. Danti, D. D’Alessandro, A. Pietrabissa, M. Petrini, S. Berrettini. J. Biomed. Mater. Res. A (2009)Google Scholar
  5. N. Datta, H.L. Holtorf, V.I. Sikavitsas, J.A. Jansen, A.G. Mikos, Biomaterials 26, 971 (2005). doi: 10.1016/j.biomaterials.2004.04.001 CrossRefGoogle Scholar
  6. N. Datta, Q.P. Pham, U. Sharma, V.I. Sikavitsas, J.A. Jansen, A.G. Mikos, PNAS 103, 2488 (2006)CrossRefGoogle Scholar
  7. K.J. Dormer, R.Z. Gan, Otolaryngol. Clin. North Am 34, 289 (2001). doi: 10.1016/S0030-6665(05)70332-7 CrossRefGoogle Scholar
  8. J.P. Fisher, T.A. Holland, D. Dean, A.G. Mikos, Biomacromol 4, 1335 (2003). doi: 10.1021/bm0300296 CrossRefGoogle Scholar
  9. E.K. Gardner, C.G. Jackson, D.M. Kaylie, Laryngoscope 114, 65 (2004). doi: 10.1097/00005537-200401000-00011 CrossRefGoogle Scholar
  10. R.A. Goldenberg, M. Driver, Otolaryngol. Head Neck Surg. 122, 635 (2000). doi: 10.1016/S0194-5998(00)70188-4 CrossRefGoogle Scholar
  11. K.J. Grande-Allen, B.P. Griffin, N.B. Ratliff, D.M. Cosgrove, I. Vesely. J. Am. Coll. Cardiol. 42, 271 (2003). doi: 10.1016/S0735-1097(03)00626-0 CrossRefGoogle Scholar
  12. J.J. Grote, Ann. Otol. Rhinol. Laryngol. Suppl 123, 10 (1986)Google Scholar
  13. J.J. Grote, W. Kuypers, K. de Groot, ORL J. Otorhinolaryngol. Relat. Spec. 43, 248 (1981)Google Scholar
  14. S.Y. Ho, R.A. Battista, R.J. Wiet, Otol. Neurotol 24, 149 (2003). doi: 10.1097/00129492-200303000-00005 CrossRefGoogle Scholar
  15. J.B. Janeke, J.J. Shea, Laryngoscope 85, 1550 (1975). doi: 10.1288/00005537-197509000-00018 CrossRefGoogle Scholar
  16. A.D. Martin, S.G. Harner, Laryngoscope 114, 61 (2004). doi: 10.1097/00005537-200401000-00010 CrossRefGoogle Scholar
  17. A.S. Mistry, S.H. Cheng, T. Yeh, E. Christenson, J.A. Jansen, A.G. Mikos, J Biomed Mater Res A. 2008 Apr 21. [Epub ahead of print]Google Scholar
  18. D. Mürbe, T. Zahnert, M. Bornitz, K.B. Hütterbrink, Laryngoscope 112, 1769 (2002). doi: 10.1097/00005537-200210000-00012 CrossRefGoogle Scholar
  19. G.F. Muschler, C. Nakamoto, L.G. Griffith, J. Bone Joint Surg. Am 86, 1541 (2004)Google Scholar
  20. H. Park, J.S. Temenoff, T.A. Holland, Y. Tabata, A.G. Mikos, Biomaterials 26, 7095 (2005). doi: 10.1016/j.biomaterials.2005.05.083 CrossRefGoogle Scholar
  21. Q.P. Pham, F.K. Kasper, L. Scott Baggett, R.M. Raphael, J.A. Jansen, A.G. Mikos, Biomaterials 29(18), 2729 (2008). doi: 10.1016/j.biomaterials.2008.02.025 CrossRefGoogle Scholar
  22. G.M. Pyle, Op Tech Otolaryngol 14, 237 (2003). doi: 10.1053/S1043-1810(03)00058-7 CrossRefGoogle Scholar
  23. E. Rondini-Gilli, A. Bozorg Grayeli, P. Fernando Tormin Borges Corsara, H. El Garem, I. Mosnier, D. Boucarra, O. Sterkers, Otol. Neurotol 24, 543 (2003). doi: 10.1097/00129492-200307000-00003 CrossRefGoogle Scholar
  24. S. Sellari-Franceschini, F. Piragine, P. Bruschini, S. Berrettini. Am. J. Otol. 8, 551 (1987)Google Scholar
  25. V.L. Singer, L.J. Jones, S.T. Yue, R.P. Haugland, Anal. Biochem 249, 228 (1997). doi: 10.1006/abio.1997.2177 CrossRefGoogle Scholar
  26. C.H. Stupp, C. Dalchow, D. Grun, H.F. Stupp, Laryngorhinootologie 78, 299 (1999). doi: 10.1055/s-2007-996875 CrossRefGoogle Scholar
  27. S.R. Taylor, L. Titus-Ernstoff, S. Stitely, Cytometry 10, 382 (1989). doi: 10.1002/cyto.990100404 CrossRefGoogle Scholar
  28. M.D. Timmer, C. Carter, C.G. Ambrose, A.G. Mikos, Biomaterials 24, 4707 (2003). doi: 10.1016/S0142-9612(03)00364-8 CrossRefGoogle Scholar
  29. M. Tos, In Manual of middle ear surgery. Thieme Medical Publishers, Inc., New York (1993) vol. 1 p. 239Google Scholar
  30. G. Vunjak-Novakovic, I. Martin, B. Obradovic, S. Treppo, A.J. Grodzinsky, R. Langer, L.E. Freed, J. Orthop. Res 17, 130 (1999). doi: 10.1002/jor.1100170119 CrossRefGoogle Scholar
  31. R.E. Wehrs, Otolaryngol. Clin. North Am 28, 273 (1995)Google Scholar
  32. H.P. Zenner, A. Stegmaier, R. Lehner, I. Baumann, R. Zimmermann. Otol. Neurotol. 22, 582 (2001). doi: 10.1097/00129492-200109000-00004 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Serena Danti
    • 1
    • 2
  • Cesare Stefanini
    • 3
  • Delfo D’Alessandro
    • 1
    • 4
  • Stefania Moscato
    • 4
  • Andrea Pietrabissa
    • 2
  • Mario Petrini
    • 1
    • 2
  • Stefano Berrettini
    • 5
  1. 1.CUCCS/RRMR (Centro per l’Uso Clinico delle Cellule Staminali/Rete Regionale di Medicina Rigenerativa)University of PisaPisaItaly
  2. 2.Department of Oncology, Transplants and Advanced TechnologiesUniversity of PisaPisaItaly
  3. 3.CRIM Lab (Center of Research In Microengineering)Scuola Superiore Sant’AnnaPontedera (Pisa)Italy
  4. 4.Department of Human Morphology & Applied BiologyUniversity of PisaPisaItaly
  5. 5.Department of Neuroscience, ENT UnitUniversity of PisaPisaItaly

Personalised recommendations