Journal of Materials Science: Materials in Medicine

, Volume 17, Issue 12, pp 1315–1322 | Cite as

Tissue reactions to bioabsorbable ciprofloxacin-releasing polylactide-polyglycolide 80/20 screws in rabbits’ cranial bone

  • Johanna Tiainen
  • Ylermi Soini
  • Esa Suokas
  • Minna Veiranto
  • Pertti Törmälä
  • Timo Waris
  • Nureddin Ashammakhi


The aim of this study was to assess tissue reactions to bioabsorbable self-reinforced ciprofloxacin-releasing polylactide/polyglycolide (SR-PLGA) 80/20 screws in rabbits’ cranial bone. Two screws were implanted in each rabbit, one screw on either side of the sagittal suture (n = 28 rabbits). Animals were sacrificed after 2, 4, 8, 16, 24, 54 and 72 weeks, four animals per group. On histological examination the number of macrophages, giant cells, active osteoblasts and fibrous tissue layers were assessed and degradation of the screws was evaluated. At 2 weeks, the highest number of macrophages and giant cells were seen near the heads of the screws. After 4 and 8 weeks, the number of giant cells decreased but that of macrophages decreased from 16 weeks and on. Screws were surrounded by fibrous tissue capsule that progressively was growing in thickness by time. Active osteoblasts were seen around the shaft of the screws with the highest number seen at 4 weeks postoperatively. At 16 weeks, compact fragmentation of the screw heads was seen with macrophages seen inside the screw matrices. After 24 weeks, no polarization of the screws was seen. After one year, PLGA screws had been replaced by adipose tissue, fibrous tissue and “foamy macrophages” which had PLGA particles inside them. After 1½ years, the amount of biomaterial remaining had decreased remarkably. The particles of biomaterial were inside “foamy macrophages.” Ciprofloxacin-releasing SR-PLGA 80/20 screws elicited a mild inflammatory reaction but did not interfere with osteoblast activity. No complications were seen when implanted in cranial bone of rabbit.


Giant Cell Active Osteoblast Cranial Bone Screw Head Sagittal Suture 
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.


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  1. 1.
    L. NIE, D. NICOLAU, P. TESSIER, H. KOUREA, B. BROWNER and C. NIGHTINGALE, Use of a bioabsorbable polymer for the delivery of ofloxacin during experimental osteomyelitis treatment. J. Orthop. Res. 16 (1998) 76–79.CrossRefGoogle Scholar
  2. 2.
    P. BECKER, R. SMITH, R. WILLIAMS and J. DUTKOWSKY, Comparison of antibiotic release from polymethylmethacrylate beads and sponge collagen. J. Orthop. Res. 12 (1994) 737–741.CrossRefGoogle Scholar
  3. 3.
    J. CALHOUN and J. MADER, Treatment of osteomyelitis with a biodegradable antibiotic implant. Clin. Orthop. 341 (1997) 206–214.CrossRefGoogle Scholar
  4. 4.
    Y. SHINTO, A. UCHIDA, F. KORKUSUZ, N. ARAKI and K. ONO, Calcium hydroxyapatite ceramic used as a delivery system for antibiotics. J. Bone. Joint. Surg. Br. 74-B (1992) 600–604.Google Scholar
  5. 5.
    J. OVERBECK, S. WINCKLER, R. MEFFERT, P. TÖRMÄLÄ, H. SPIEGEL and E. BRUG, Penetration of ciprofloxacin into bone: A new bioabsorbable implant. J. Invest. Surg. 8 (1995) 155–162.Google Scholar
  6. 6.
    E. JACOB, J. SETTERSTRÖM, D. BACH, J. R. HEATH, L. MCNIESH and G. CIERNY, Evaluation of biodegradable ampicillin anhydrate microcapsules for local treatment of experimental staphylococcal osteomyelitis. Clin. Orthop. 267 (1991) 237–244.Google Scholar
  7. 7.
    P. OSTERMANN, S. HENRY and D. SELIGSON, The role of local antibiotic therapy in the management of compound fractures. Clin. Orthop. 295 (1993) 102–111.Google Scholar
  8. 8.
    M. GÜMÜ SDERELIOGLU and G. DENIZ, Sustained release of mitomycin-C from poly (DL-lactide) /poly (DL-lactide-co-glycolide) films. J. Biomater. Sci. 11 (2000) 1039–1050.CrossRefGoogle Scholar
  9. 9.
    C. TEUPE, R. MEFFERT, S. WINCKLER, W. RITZERFELD, P. TÖRMÄLÄ and E. BRUG, Ciprofloxacin-impregnated poly-L-lactic acid drug carrier. New aspects of a resorbable drug delivery system in local antimicrobial treatment of bone infections. Arch. Orthop. Trauma Surg. 112 (1992) 33–35.CrossRefGoogle Scholar
  10. 10.
    J. TIAINEN, M. VEIRANTO, E. SUOKAS, P. TÖRMÄLÄ and T. WARIS, M. Ninkovic and N. Ashammakhi, Bioabsorbable ciprofloxacin-containing and plain self-reinforced polylactide-polyglycolide 80/20 screws: pull-out strength properties in human cadaver parietal bones. J. Craniofac. Surg. 13 (2002) 427–433.CrossRefGoogle Scholar
  11. 11.
    S. LEINONEN, E. SUOKAS, M. VEIRANTO, P. TÖRMÄLÄ, T. WARIS and N. ASHAMMAKHI, Holding power of bioabsorbable ciprofloxacin-containing self-reinforced poly-L/DL-lactide 70/30 bioactive glass 13 miniscrews in human cadaver bone. J. Craniofac. Surg. 13 (2002) 212–218.CrossRefGoogle Scholar
  12. 12.
    N. ASHAMMAKHI, Neomembranes: A concept review with special reference to self-reinforced polyglycolide membranes. J. Biomed. Mater. Res. [Appl. Biomater.] 33 (1996) 297–303.CrossRefGoogle Scholar
  13. 13.
    B. EPPLEY and M. SADOVE, A comparison of resorbable and metallic fixation in healing of calvarial bone grafts. Plast. Reconstr. Surg. 96 (1995) 316–322.CrossRefGoogle Scholar
  14. 14.
    M. VEIRANTO, E. SUOKAS, N. ASHAMMAKHI and P. TÖRMÄLÄ, Novel bioabsorbable antibiotic releasing bone fracture fixation implants. Adv. Exp. Med. Biol. 553 (2004) 197–208.Google Scholar
  15. 15.
    S.-M. NIEMELÄ, I. IKÄ HEIMO, M. KOSKELA, M. VEIRANTO, E. SUOKAS, P. TÖRMÄLÄ, T. WARIS, N. ASHAMMAKHI and H. SYRJÄ LÄ, Ciprofloxacin-releasing bioabsorbable polymer is superior to titanium in preventing Staphylococcus epidermis attachment and biofilm formation in vitro. J. Biomed. Mater. Res. [Appl. Biomater.] (Accepted) .Google Scholar
  16. 16.
    J. KITCHELL and D. WISE, Poly(lactic/glycolic acid) biodegradable drug-polymer matrix systems. Methods Enzymol. 112 (1985) 436–448.CrossRefGoogle Scholar
  17. 17.
    S. HUMPHREY, S. MEHTA, A. SEABER and T. VAIL, Pharmacokinetics of a degradable drug delivery system in bone. Clin. Orthop. 349 (1998) 218–224.Google Scholar
  18. 18.
    M. VERT, M. LI, G. SPENLEHAUER and P. GUERIN, Bioresorbability and biocompatibility of aliphatic polyesters. J. Mater. Sci. Mater. Med. 3 (1992) 432–446.CrossRefGoogle Scholar
  19. 19.
    P. TÖRMÄLÄ, Biodegradable self-reinforced composite materials; manufacturing structure and mechanical properties. Clin. Mater. 10 (1992) 29–34.CrossRefGoogle Scholar
  20. 20.
    W. PIETRZAK, D. SARVER and M VERSTYNEN, Bioabsorbable polymer science for the practicing surgeon. J. Craniofac. Surg. 8 (1997) 87–91.Google Scholar
  21. 21.
    K. KNUUTILA, J. TIAINEN, M. VEIRANTO, E. SUOKAS, T. WARIS, P. TÖRMÄLÄ, O. KAARELA and N. ASHAMMAKHI, Pull-Out Strength Properties of Antibiotic Releasing Tacks in Human Cadaver Bone. Society for Biomaterials Symposium on Biomaterials in Regenerative Medicine: The Advent of Combination Products, Philadelphia, Pennsylvania, USA, 10 (2004) 16–18.Google Scholar
  22. 22.
    P. D. HOLTOM, S. A. PAVKOVIC, P. D. BRAVOS, M. J. PATZAKIS, L. E. SHEPHERD and B. FRENKEL, Inhibitory effects of the quinolone antibiotics trovafloxacin, ciprofloxacin, and levofloxacin on osteoblastic cells in vitro. J. Orthop. Res. 18 (2000) 721–727.CrossRefGoogle Scholar
  23. 23.
    T. MICLAU, M. L. EDIN, G. E. LESTER, R. W. LINDSEY and L. E. DAHNERS, Effect of ciprofloxacin on the proliferation of osteoblast-like MG-63 human osteosarcoma cells in vitro. J. Orthop. Res. 16 (1998) 509–512.CrossRefGoogle Scholar
  24. 24.
    A. C. PERRY, B. PRPA, M. S. ROUSE, K. E. PIPER, A. D. HANSSEN, J. M. STECKELBERG and R. PATEL, Levofloxacin and trovafloxacin inhibition of experimental fracture-healing. Clin. Orthop. 414 (2003) 95–100.Google Scholar
  25. 25.
    N. ASHAMMAKHI, H. PELTONIEMI, E. WARIS, R. SUURONEN, W. SERLO, M. KELLOMäKI, P. TÖRMÄLÄ and T. WARIS, Developments in craniomaxillofacial surgery: Use of self-reinforced polyglycolide and polylactide osteofixation devices. Review. Plast. Reconstr. Surg. 108 (2001) 167–180.CrossRefGoogle Scholar
  26. 26.
    J. HUNT and D. WILLIAMS, Quantifying the soft tissue response to implanted materials. Biomaterials. 16 (1995) 167–170.CrossRefGoogle Scholar
  27. 27.
    J. TIAINEN, Y. SOINI, P. TÖRMÄLÄ, T. WARIS and N. ASHAMMAKHI, Self-reinforced polylactide-polyglycolide 80/20 screws take more than 1 1/2 years to resorb in rabbit cranial bone. J. Biomed. Mater. Res. [Appl. Biomater.] 70B (2004) 49–55.CrossRefGoogle Scholar
  28. 28.
    M. HABAL and W. PIETRZAK, Key points in the fixation of the craniofacial skeleton with absorbable biomaterial. J. Craniofac. Surg. 10 (1999) 491–499.CrossRefGoogle Scholar
  29. 29.
    N. ASHAMMAKHI, Editorial. Reactions to Biomaterials: the Good, the Bad and Ideas for Developing New Therapeutic Approaches. J. Craniofac. Surg. 16 (2005) 195.CrossRefGoogle Scholar
  30. 30.
    G. VINCE, J. HUNT and D. WILLIAMS, Quantitative assessment of the tissue response to implanted biomaterials. Biomaterials. 12 (1991) 731–736.CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Johanna Tiainen
    • 1
    • 5
  • Ylermi Soini
    • 2
  • Esa Suokas
    • 3
  • Minna Veiranto
    • 4
  • Pertti Törmälä
    • 4
  • Timo Waris
    • 1
  • Nureddin Ashammakhi
    • 1
    • 4
  1. 1.Department of SurgeryOulu University HospitalOuluFinland
  2. 2.Department of PathologyOulu University HospitalOuluFinland
  3. 3.Linvatec Biomaterials Ltd.TampereFinland
  4. 4.Institute of BiomaterialsTampere University of TechnologyTampereFinland
  5. 5.Division of Plastic Surgery, Department of SurgeryOulu University HospitalOuluFinland

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