Multiphasic Biomaterials: A Concept for Bone Substitutes Developed in the "Pays de la Loire"


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This paper reports on the research into multiphase bone substitutes carried out by laboratories from the ‘Pays de la Loire’ region in France. This collaborative research was funded by both the French Government and the Regional Council in the period 2000-2007. Calcium phosphate bioceramics, polymers and combinations have been developed as bone substitutes for various maxillofacial and orthopaedic applications. These bone substitutes should support and regenerate bone tissue and resorb after implantation. In the bone tissue engineering area, they have been combined with autologous bone marrow cells or bioactive factors. The bone substitutes were tested in various animal models mimicking clinical situations or under pathological conditions (osteoporosis). In order to complete our research, the multiphase materials were also evaluated in clinical trials.



Key Engineering Materials (Volumes 361-363)

Main Theme:

Edited by:

Guy Daculsi and Pierre Layrolle


G. Daculsi et al., "Multiphasic Biomaterials: A Concept for Bone Substitutes Developed in the "Pays de la Loire"", Key Engineering Materials, Vols. 361-363, pp. -17--1, 2008

Online since:

November 2007




[1] Moreau MF, Gallois Y, Basle MF, Chappard D (2000) Biomaterials 21: 369-76.

[2] Dumas A, Gaudin-Audrain C, Mabilleau G, Massin P, Hubert L, Basle MF, Chappard D (2006). Biomaterials 27: 4204-11.


[3] Albee FH (1920). Ann Surg 71: 32-36.

[4] Nery EB, Lynch KL, Hirthe WM, Mueller KH (1975). J. Periodontol. 63: 729-735.

[5] Denissen, H.W. (1979) PhD Thesis, Amsterdam, Vrije Universiteit.

[6] Jarcho M. (1981). Clin Orthop 157: 259-278.

[7] De Groot K. (1983). In: Bioceramics of Calcium Phosphates. CRC Press, Boca Raton, 100-114.

[8] Metsger SD, Driskell TD, Paulsrud JR(1982). J Am. Dent. Assoc 105: 1035-1048.

[9] Aoki , H, Kato, K (1975). Jpn. Ceram. Soc. 10: 469.

[10] Daculsi G. (1998). Biomaterials, 19: 1473-1478.

[11] LeGeros RZ, Nery E, Daculsi G, Lynch K, Kerebel B. (1988). Third World Biomaterials Congress (abstract no. 35). 12 Daculsi G., LeGeros RZ, Nery E., Lynch K , Kerebel B. (1989). J Biomed Mat Res 23: 883-894.


[13] Daculsi G., Passuti, N. (1990). Biomaterials 11: 86-87.

[14] Trecant, M., Delecrin, J., Royer, J. Goyenvalle, E., Daculsi, G. (1994). Clin Mater. 15: 233-240.


[15] LeGeros RZ, Lin S, Rohanizadeh R, Mijares D, LeGeros JP (2003). J. Mater. Sci.: Mat in Med 14: 201-210.


[16] Hench L.L., Splinter R.J., Allen W.C. Greelee T.K. (1978). J Biomed Mater Res 2: 117-141.

[17] Daculsi G., LeGeros RZ., Heugheaert M., Barbieux. I. (1990). Calcif Tissue Int 46: 20-27.

[18] Daculsi G., (2006). Advances in Science and Technology Volume 49, Trans Tech Publications, Switzerland, pp.9-13.

[19] Daculsi G, Weiss P, Bouler JM, Gauthier O, Aguado E . (1999), Bone, 25: 59-61.

[20] Daculsi G, Khairoun I, LeGeros RZ, Moreau F, Pilet P, Bourges X, Weiss P, Gauthier O (2006). Key Engineering Materials 330-332: 811-814.


[21] Daculsi G, Layrolle P. (2004) Key Engineering Materials vols. 254-256, pp.1005-1009.

[22] Le Nihouannen D, Daculsi G, Saffarzadeh A, Gauthier O, Delplace S, Pilet P, Layrolle P. (2005) s. Bone 36/6: 1086-1093.


[23] Yuan H, Van Den Doel M, Li S, Van Blitterswijk CA, de Groot K, de Bruijn JD. (2002) J. Mater. Sci. Mater. Med. 13 127.

[24] Habibovic P, Li JP, Van Der Valk CM, Meijer G, Layrolle P, Van Blitterswijk CA, de Groot K. (2005) Biomaterials 26 23.


[25] Ripamonti U. Biomaterials 17 (1996) 31.

[26] Fellah BH, Josselin N, Chappard D, Weiss P (2007) . J Mater Sci: Mater Med.; 18: 285-292.

[27] LeGeros RZ, Chohayeb A, Shulman A (1982). Apatitic calcium phosphates: possible restorative materials. J Dent Res 61 (spec issue): 343.

[28] Brown WE, Chow LC (1987). in Brown PW (ed). Cement Research Progress 1986. Americin Ceramic Society, Westerville, OH pp.352-379.

[29] Khairoun I., Magne D., Gauthier O., Bouler J-M., Aguado E., Daculsi G. and Weiss P. (2002) J Biomed Mater Res 15; 60(4): 633-42.

[30] Weiss P, Obadia L, Magne D, Bourges X, Rau C, Weitkamp T, Khairoun I, Bouler J-M, Chappard D, Gauthier O, Daculsi G. (2003) Biomaterials 24(25): 4591-601.


[31] Niwa S, LeGeros RZ (2002).

[32] Constanz B.R., Ison I.C., Fulmer M.T., Poser R.D., Smith S.T. Van Wagoner M. Ross J. Goldstein S.A. (1995) Science 267: 1796-1799.

[33] Khairoun I, LeGeros RZ, Daculsi G, Bouler JM, Guicheux J, Gauthier O (2004).

[34] Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999).

[36] Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP(1997). J Cell Biochem 64: 295-312.

[37] Bruder SP, Jaiswal N, Haynesworth SE (1997):. J Cell Biochem 64: 278-294.

[38] Kadiyala S, Jaiswal N, Bruder SP (1997). Tissue Engineering 3: 173-185.

[39] Livingston Arinzeh T., Peter S, Archambault M, Van Den Bos C, Gordon S, Kraus K, Smith A, Kadiyala S (2003). Journal of Bone and Joint Surgery American 85-A: 1927-(1935).


[40] Daculsi G., (2006). High performance of new interconnected MicroMacroporous Biphasic Calcium Phosphate matrices MBCP2000 for bone tissue engineering Proceedings 20 th European Conference on Biomaterials, Nantes France.

[41] Monthéard JP, Kahovec J, Chappard D (1997). In: Arshady R (ed. ) Desk reference of functional polymers; Syntheses and applications. American Chemical Society, Washington DC, pp.699-717.

[42] Zainuddin, Hill DJ, Whittaker AK, Lambert L, Chirila TV (2007). J Mater Sci Mater Med.

[43] Filmon R, Chappard D, Monthéard JP, Baslé MF (1996) Cells and Materials 6: 11-20.

[44] Filmon R, Baslé MF, Barbier A, Chappard D (2000). J. Biomat. Sci. Polymer Edition 11: 849-868.

[45] Filmon R, Baslé MF, Barbier A, Chappard D (2000). Morphologie 84: 23-33.

[46] Filmon R, Grizon F, Basle MF, Chappaard D 2002. Biomaterials 23: 3053-9.

[47] Filmon R, Baslé MF, A®ani H, Chappard D (2002) Adherence of osteoblast-like cells on calcospherites developed on a biomaterial combining poly(2-hydroxyethyl) methacrylate and alkaline phosphatase. Bone 30: 152-158.


[48] Stancu IC, Filmon R, Cincu C, Marculescu B, Zaharia C, Tourmen Y, Baslé MF, Chappard D (2004). Biomaterials 25: 205-13.


[49] Stancu IC, Filmon R, Grizon F, Zaharia C, Cincu C, Baslé MF, Chappard D (2004). J Biomed Mater Res A 69: 584-589.


[50] Filmon R, Retailleau-Gaborit N, Grizon F, Galloyer M, Cincu C, Basle MF, Chappard D 2002 Nonconnected versus interconnected macroporosity in poly(2-hydroxyethyl methacrylate) polymers. An X-ray microtomographic and histomorphometric study. J Biomater Sci Polym Ed 13: 1105-17.


[51] Stancu IC, Layrolle P, Filmon R, Legeay G, Cincu C, Baslé MF, Chappard D (2007). J Optoelectr Adv Mater: accepted for publication.

[52] Mabilleau G, Stancu IC, Honore T, Legeay G, Cincu C, Basle MF, Chappard D 2006. J Biomed Mater Res A 77: 35-42.


[53] Mabilleau G, Moreau MF, Filmon R, Basle MF, Chappard D 2004. Biomaterials 25: 5155-62.


[54] Gauthier O, Goyenvalle E, Bouler J-M., Guicheux J., Pilet P. Weiss P. And Daculsi G. ( 2001) J Mater Sci Mater Med 12 : 385-390.


[55] Daculsi G., Weiss P., Bouler J.M., Gauthier O., Aguado E. (1999) Bone, 25: 59-61.

[56] Gauthier O, Bouler JM, Aguado E, Legeros Rz, Pilet P, Daculsi G. (1999) J of Mater Sc : Mat in Med, , 10: 199-204.


[57] Gauthier O, Bouler Jm, Weiss P, Bosco J, Daculsi G, Aguado E. (1999). . J Biomed Mater Res, 1999, 47(1) : 28-35 58 Gauthier O., Bouler J.M., Weiss P., Bosco J., Aguado E., Daculsi G. (1999). Bone, 25: 71-74.


[59] Gauthier O, Muller R, Von Stechow D, Lamy B, Weiss P, Bouler J-M, Aguado E and Daculsi G. (2005) Biomaterials 26: 5444-53.

[60] Lapkowski M, Weiss P, Daculsi G et Dupraz A. (1997), international patent, WO 97/05911.

[61] Turczyn R, Weiss P, Lapkowski M, Daculsi G. (2000) J Biomater Sci Polym Ed.; 11(2): 217-23.

[62] Bourges X, Weiss P, Daculsi G And Legeay G (2003). Advanced colloid and interface science. 99 (3): 215-228.

[63] Fellah BH, Weiss P, Gauthier O, Rouillon T, Pilet P, Daculsi G, Layrolle P. (2006). J Orthop Res; 24(4): 628-35.

[64] LeNihouannen DL, Saffarzadeh A, Aguado E, Goyenvalle E, Gauthier O, Moreau F, Pilet P, Spaethe R, Daculsi G, Layrolle P. J (2007). J Mater Sci Mater Med. 2007 Feb; 18(2): 225-235.


[65] Le Guehennec L, Layrolle P, Daculsi G (2004). Eur Cell Mater. 2004 Sep 13; 8: 1-11.

[66] Audran M, Chappard D, Legrand E, Libouban H, Baslé MF (2001). Calcif Tissue Int 69: 214-7.

[67] Libouban H, Moreau MF, Legrand E, Audran M, Baslé MF, Chappard D (2002) Osteoporos Int 13: 422-8.

[68] Libouban H, Moreau MF, Legrand E, Baslé MF, Audran M, Chappard D (2001) Calcif Tissue Int 68: 31-7.

[69] Libouban H, Simon Y, Silve C, Legrand E, Baslé MF, Audran M, Chappard D (2002). J Clin Densitom 5: 355-61.

[70] Chappard D, Chennebault A, Moreau M, Legrand E, Audran M, Baslé MF (2001) Bone 28: 72-9.

[71] Blouin S, Gallois Y, Moreau MF, Baslé MF, Chappard D (2007). Osteoporos Int 18: 85-92.

[72] Blouin S, Moreau MF, Weiss P, Daculsi G, Baslé MF, Chappard D (2006). J Biomed Mater Res A 78: 570-80.

[73] Clemencia Rodríguez M, Jean A., Kimakhe S., Sylvia Mitja S., Daculsi G., (2007). Proceedings IADR 2007, New Orleans.

[74] Clemencia Rodríguez M, Jean A., Kimakhe S., Sylvia Mitja S., Daculsi G., (2007). Key Engineering Materials vols 333-334 (2007), in press, Trans Tech Publication Switzerland.

[75] Weiss P, Clergeau L P, Enckel B, Amouriq Y, Giumelli B, Jean A And Daculsi G. (2004). Key Engineering Materials 2004; 284-286 : 1053-1056.


[76] Weiss P, Layrolle P, Clergeau Lp, Enckel E, Pilet P , Amouriq Y , Daculsi G And Giumelli B. (2007) l. Biomaterials. 2007 Nov 2. Aug; 28(22): 3295-305.


[77] DaculsiG., Weiss P., Delecrin J., Grimandi G., Passuti N., Guerin F., (1994) Patent n° 94-01-414 1994235, WO 95/21634 Composition pour biomatériaux - procédés de preparation.

[78] Daculsi G., Weiss P., Bouler J.M., Gauthier O., Aguado E. (1999) Biomaterials, Bone, 25: 59-61.

[79] Millot F., Grimandi G., Weiss P. Daculsi G. (1999). Cells and Mat. 9: 21-30.

[80] Dupraz A, Nguyen TP, Richard M, Daculsi G, Passuti N. (1999). Biomaterials, , 20: 663-673.

[81] Gauthier O, Boix D, Grimandi G, Aguado E, Bouler Jm, Weiss P, Daculsi G . (1999). J Periodontol,; 70: 375-383.

[82] LeGeros RZ (1993). Clin. Mater. 14 : 65-88. 83 Boix D, Weiss P, Gauthier O, Guicheux J, Bouler JM, Pilet P, Daculsi G, Grimandi G.J. (2006) J Mater Sci Mater Med. Nov; 17(11): 1145-52.


[84] Malard O, Bouler Jm, Guicheux J, Heymann D, Pilet P, Coquard C, Daculsi G. (1999). J Biomed Mater Res, 46 : 103-111.


[85] Daculsi, G. Passuti, N. Martin, S., Deudon, C. LeGeros, R.Z. (1990). J Biomed. Mater. Res. 24: 379 396.

[86] Daculsi, G., Bagot D'arc, M., Corlieu , P., Gersdorff, M. (1992). Ann Orol. Rhinol Laryngol 101: 669-674.

[87] Gouin, F., Delecrin, J., Passuti, N., Touchais, S., Poirier, P, Bainvel, J.V. (1995). Rev Chir Orthop 81: 59-65.

[88] Ransford A.O., Morley T., Edgar M.A., Webb P., Passuti N., Chopin D., Morin C., Michel F., Garin C., Pries D. (1998).

[89] Cavagna, R., Daculsi, G., Bouler, J-M., (1999). Long term Effects Med Impl 9 : 403-412.

[90] Soares EJC, Franca VP, Wykrota L, Stumpf S. (1998). In LeGeros RZ, LeGeros JP (Eds) Bioceramics 11, Singapore, World Scientific, pp.633-636.

[91] Wykrota LL, Garrido CA, Wykrota FHI (1998). In LeGeros RZ, LeGeros JP (Eds) Bioceramics 11, Singapore, World Scientific, pp.641-644.

[92] Delecrin J, Takahashi S, Gouin F, Passuti N (2000). Spine 25: 563-569.

[93] Shima T., Keller J.T., Alvira M.M., Mayfield F.H., Dunker S.B. (1979) J. Neurosurg., 51 : 533-8.

[94] Toth J.M., An H.S., Lim T.H., Ran Y., Weiss N.G., Lundberg W.R., Xu R.M., Lynch K.L. (1995). Spine, 20(20), 2203-10.

[95] Zdeblick T.A., Cooke M.E., Wilson D., Kunz D.N., McCabe R. (1993). Spine, 18(14) : 1974-83.

[96] Zdeblick T.A., Ghanayem A.J., Rapoff A.J., Swain C., Basset T., Cooke M.E., Markel M. (1998) Spine, 23 : 758-65.

[97] Pascal-Moussellard H., Catonné Y., R. Robert R., Daculsi G., (2007). Proceedings ESB 20, Nantes France.

[98] Lascart T, Favard L, Burdin P, Traoré O. (1998) Ann Orthop Ouest; 30: 137-141.

[99] Bonnevialle P, Abid A, Mansat P, Verhaeghe L, Clement D, Mansat M. (2002) Rev Chir Orthop; 88: 486-492. 100Koshino T, Murase T, Saito T. (2003) J Bone Joint Surg [Am. ]; 85-A: 78-85. 101Rouvillain J.L. (2007). Proceedings ESB 20, Nantes France.