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Characterisation of a new bioadhesive system based on polysaccharides with the potential to be used as bone glue

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Abstract

Although gluing bone is in theory a very attractive alternative to classical fracture treatment, this method is not yet clinically established due to the lack of an adhesive which would meet all the necessary requirements. We therefore developed a novel two-component bioadhesive system with the potential to be used as a bone adhesive based on biocompatible and degradable biopolymers (chitosan, oxidised dextran or starch). After mixing in water, the two components covalently cross-link by forming a Schiff’s base. By the same mechanism, the glue binds to any other exposed amino group such as for example those exposed in fractured bone, even in the presence of water. Modified chitosan was synthesised from commercially available chitosan by deacetylation and was then reduced in molecular weight by heating in acid. The amount of free amino groups was analysed by IR. The molecular weight was determined by viscosimetry. Starch or dextran were oxidised with periodic acid to generate aldehyde groups, which were quantified by titration. l-Dopa was conjugated to oxidised dextran or starch in analogy to the gluing mechanism of mussels. Biomechanical studies revealed that the new glue is superior to fibrin glue, but has less adhesive strength than cyanoacrylates. In vitro cell testing demonstrated excellent biocompatibility, rendering this glue a potential candidate for clinical use.

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References

  1. Heiss C, Schnettler R. Bioresorbierbare Klebstoffe in der operativen Traumatologie und Orthopädie. BIOmaterialien. 2003;4:298–304.

    Google Scholar 

  2. Sung HW, Huang DM, Chang WH, Huang RN, Hsu JC. Evaluation of gelatin hydrogel crosslinked with various crosslinking agents as bioadhesives: in vitro study. J Biomed Mater Res. 1999;46(4):520–30. doi:10.1002/(SICI)1097-4636(19990915)46:4<520::AID-JBM10>3.0.CO;2-9.

    Article  PubMed  CAS  Google Scholar 

  3. Iwata H, Matsuda S, Mitsuhashi K, Itoh E, Ikada Y. A novel surgical glue composed of gelatin and N-hydroxysuccinimide activated poly(l-glutamic acid): Part 1. Synthesis of activated poly(l-glutamic acid) and its gelation with gelatin. Biomaterials. 1998;19(20):1869–76. doi:10.1016/S0142-9612(98)00095-7.

    Article  PubMed  CAS  Google Scholar 

  4. Mo X, Iwata H, Matsuda S, Ikada Y. Soft tissue adhesive composed of modified gelatin and polysaccharides. J Biomater Sci Polym Ed. 2000;11(4):341–51. doi:10.1163/156856200743742.

    Article  PubMed  CAS  Google Scholar 

  5. Matsuda S, Iwata H, Se N, Ikada Y. Bioadhesion of gelatin films crosslinked with glutaraldehyde. J Biomed Mater Res. 1999;45(1):20–7. doi:10.1002/(SICI)1097-4636(199904)45:1<20::AID-JBM3>3.0.CO;2-6.

    Article  PubMed  CAS  Google Scholar 

  6. Taguchi T, Saito H, Uchida Y, Sakane M, Kobayashi H, Kataoka K, et al. Bonding of soft tissues using a novel tissue adhesive consisting of a citric acid derivative and collagen. Mater Sci Eng C. 2004;24(6–8):775–80. doi:10.1016/j.msec.2004.08.037.

    Article  CAS  Google Scholar 

  7. Sekine T, Nakamura T, Shimizu Y, Ueda H, Matsumoto K, Takimoto Y, et al. A new type of surgical adhesive made from porcine collagen and polyglutamic acid. J Biomed Mater Res. 2001;54(2):305–10. doi:10.1002/1097-4636(200102)54:2<305::AID-JBM18>3.0.CO;2-B.

    Article  PubMed  CAS  Google Scholar 

  8. Goldmann H, Wegmann J, Inventor; Aesculap AG & Co. KG, 78532 Tuttlingen, DE assignee. Zusammensetzung aus mindestens zwei biokompatiblen chemisch vernetzbaren Komponenten. Germany patent DE000010152407A1. 2001, 2003 May 1.

  9. Sung HW, Chen CN, Liang HF, Hong MH. A natural compound (reuterin) produced by Lactobacillus reuteri for biological-tissue fixation. Biomaterials. 2003;24(8):1335–47. doi:10.1016/S0142-9612(02)00509-4.

    Article  PubMed  CAS  Google Scholar 

  10. Zehr KJ. Use of bovine albumin-glutaraldehyde glue in cardiovascular surgery. Ann Thorac Surg. 2007;84(3):1048–52. doi:10.1016/j.athoracsur.2007.01.012.

    Article  PubMed  Google Scholar 

  11. Donkerwolcke M, Burny F, Muster D. Tissues and bone adhesives—historical aspects. Biomaterials. 1998;19(16):1461–6. doi:10.1016/S0142-9612(98)00059-3.

    Article  PubMed  CAS  Google Scholar 

  12. Heiss C, Hahn N, Wenisch S, Alt V, Pokinskyj P, Horas U, et al. The tissue response to an alkylene bis(dilactoyl)-methacrylate bone adhesive. Biomaterials. 2005;26(12):1389–96. doi:10.1016/j.biomaterials.2004.04.048.

    Article  PubMed  CAS  Google Scholar 

  13. Heiss C, Hahn N, Pokinskyj P, Wenisch S, Stahl JP, Meyer C, et al. Properties and degradation of a new bioresorbable bone glue. Biomed Tech (Berl). 2004;49(6):163–9. doi:10.1515/BMT.2004.031.

    Article  CAS  Google Scholar 

  14. Montanaro L, Arciola CR, Cenni E, Ciapetti G, Savioli F, Filippini F, et al. Cytotoxicity, blood compatibility and antimicrobial activity of two cyanoacrylate glues for surgical use. Biomaterials. 2001;22(1):59–66. doi:10.1016/S0142-9612(00)00163-0.

    Article  PubMed  CAS  Google Scholar 

  15. Khor E. Chitin: fulfilling a biomaterials promise. 1st ed. Amsterdam: Elsevier; 2001.

    Google Scholar 

  16. Madihally SV, Matthew HW. Porous chitosan scaffolds for tissue engineering. Biomaterials. 1999;20(12):1133–42. doi:10.1016/S0142-9612(99)00011-3.

    Article  PubMed  CAS  Google Scholar 

  17. Fakhry A, Schneider GB, Zaharias R, Senel S. Chitosan supports the initial attachment and spreading of osteoblasts preferentially over fibroblasts. Biomaterials. 2004;25(11):2075–9. doi:10.1016/j.biomaterials.2003.08.068.

    Article  PubMed  CAS  Google Scholar 

  18. Yu M, Deming TJ. Synthetic polypeptide mimics of marine adhesives. Macromolecules. 1998;31(15):4739–45. doi:10.1021/ma980268z.

    Article  PubMed  ADS  CAS  Google Scholar 

  19. Deming TJ. Mussel byssus and biomolecular materials. Curr Opin Chem Biol. 1999;3(1):100–5. doi:10.1016/S1367-5931(99)80018-0.

    Article  PubMed  CAS  Google Scholar 

  20. Yu M, Hwang J, Deming TJ. Role of l-3, 4-dihydroxyphenylalanine in mussel adhesive proteins. J Am Chem Soc. 1999;121(24):5825–6. doi:10.1021/ja990469y.

    Article  CAS  Google Scholar 

  21. Rinaudo M, Milas M, Le Dung P. Characterization of chitosan. Influence of ionic strength and degree of acetylation on chain expansion. Int J Biol Macromol. 1993;15(5):281–5. doi:10.1016/0141-8130(93)90027-J.

    Article  PubMed  CAS  Google Scholar 

  22. Hoffmann B, Volkmer E, Kokott A, Weber M, Hamisch S, Schieker M, et al. A new biodegradable bone wax substitute with the potential to be used as a bone filling material. J Mater Chem. 2007;17(38):4028–33. doi:10.1039/b707992n.

    Article  CAS  Google Scholar 

  23. Ninan L, Monahan J, Stroshine RL, Wilker JJ, Shi R. Adhesive strength of marine mussel extracts on porcine skin. Biomaterials. 2003;24(22):4091–9. doi:10.1016/S0142-9612(03)00257-6.

    Article  PubMed  CAS  Google Scholar 

  24. Hwang JJ, Stupp SI. Poly(amino acid) bioadhesives for tissue repair. J Biomater Sci Polym Ed. 2000;11:1023–38. doi:10.1163/156856200743553.

    Article  PubMed  CAS  Google Scholar 

  25. Reiner RH, Batz HG. HIO4 oxidized soluble polysaccharides as polyfunctional links for covalent binding of enzymes, 1. Preparation of polysaccharides and matrices for their binding. Makromol Chem. 1981;182(6):1641–8.

    Article  CAS  Google Scholar 

  26. Levine S, Griffin HL, Senti FR. Solution properties of dialdehyde starch. J Polym Sci. 1959;35(128):31–42. doi:10.1002/pol.1959.1203512804.

    Article  CAS  Google Scholar 

  27. Abdel-Fattah WI, Jiang T, El-Bassyouni Gel T, Laurencin CT. Synthesis, characterization of chitosans and fabrication of sintered chitosan microsphere matrices for bone tissue engineering. Acta Biomater. 2007;3(4):503–14. doi:10.1016/j.actbio.2006.12.004.

    Article  PubMed  CAS  Google Scholar 

  28. Wanjun T, Cunxin W, Donghua C. Kinetic studies on the pyrolysis of chitin and chitosan. Polym Degrad Stabil. 2005;87(3):389–94. doi:10.1016/j.polymdegradstab.2004.08.006.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by Synos-Foundation (Nr. 2003 0107-02). We thank Prof. G. Platz (PCI, University of Bayreuth) for discussion and the possibility to use the Ubbelohde viscosimeter.

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Correspondence to Bettina Hoffmann.

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Bettina Hoffmann and Elias Volkmer contributed equally to this work.

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Hoffmann, B., Volkmer, E., Kokott, A. et al. Characterisation of a new bioadhesive system based on polysaccharides with the potential to be used as bone glue. J Mater Sci: Mater Med 20, 2001–2009 (2009). https://doi.org/10.1007/s10856-009-3782-5

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  • DOI: https://doi.org/10.1007/s10856-009-3782-5

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