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.
Similar content being viewed by others
References
Heiss C, Schnettler R. Bioresorbierbare Klebstoffe in der operativen Traumatologie und Orthopädie. BIOmaterialien. 2003;4:298–304.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Khor E. Chitin: fulfilling a biomaterials promise. 1st ed. Amsterdam: Elsevier; 2001.
Madihally SV, Matthew HW. Porous chitosan scaffolds for tissue engineering. Biomaterials. 1999;20(12):1133–42. doi:10.1016/S0142-9612(99)00011-3.
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.
Yu M, Deming TJ. Synthetic polypeptide mimics of marine adhesives. Macromolecules. 1998;31(15):4739–45. doi:10.1021/ma980268z.
Deming TJ. Mussel byssus and biomolecular materials. Curr Opin Chem Biol. 1999;3(1):100–5. doi:10.1016/S1367-5931(99)80018-0.
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.
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.
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.
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.
Hwang JJ, Stupp SI. Poly(amino acid) bioadhesives for tissue repair. J Biomater Sci Polym Ed. 2000;11:1023–38. doi:10.1163/156856200743553.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
Bettina Hoffmann and Elias Volkmer contributed equally to this work.
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10856-009-3782-5