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Journal of Zhejiang University SCIENCE B 2011 Vol.12 No.7 P.582-590


Osteoinduction by Ca-P biomaterials implanted into the muscles of mice

Author(s):  Rui-na Yang, Feng Ye, Li-jia Cheng, Jin-jing Wang, Xiao-feng Lu, Yu-jun Shi, Hong-song Fan, Xing-dong Zhang, Hong Bu

Affiliation(s):  Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu 610041, China, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China, Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China

Corresponding email(s):   hongbu@scu.edu.cn

Key Words:  Osteoinduction, Hydroxyapatite/β, -tricalcium phosphate, Biphasic calcium phosphate, Osteogenesis

Rui-na Yang, Feng Ye, Li-jia Cheng, Jin-jing Wang, Xiao-feng Lu, Yu-jun Shi, Hong-song Fan, Xing-dong Zhang, Hong Bu. Osteoinduction by Ca-P biomaterials implanted into the muscles of mice[J]. Journal of Zhejiang University Science B, 2011, 12(7): 582-590.

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author="Rui-na Yang, Feng Ye, Li-jia Cheng, Jin-jing Wang, Xiao-feng Lu, Yu-jun Shi, Hong-song Fan, Xing-dong Zhang, Hong Bu",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Osteoinduction by Ca-P biomaterials implanted into the muscles of mice
%A Rui-na Yang
%A Feng Ye
%A Li-jia Cheng
%A Jin-jing Wang
%A Xiao-feng Lu
%A Yu-jun Shi
%A Hong-song Fan
%A Xing-dong Zhang
%A Hong Bu
%J Journal of Zhejiang University SCIENCE B
%V 12
%N 7
%P 582-590
%@ 1673-1581
%D 2011
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1000204

T1 - Osteoinduction by Ca-P biomaterials implanted into the muscles of mice
A1 - Rui-na Yang
A1 - Feng Ye
A1 - Li-jia Cheng
A1 - Jin-jing Wang
A1 - Xiao-feng Lu
A1 - Yu-jun Shi
A1 - Hong-song Fan
A1 - Xing-dong Zhang
A1 - Hong Bu
J0 - Journal of Zhejiang University Science B
VL - 12
IS - 7
SP - 582
EP - 590
%@ 1673-1581
Y1 - 2011
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1000204

The osteoinduction of porous biphasic calcium phosphate ceramics (BCP) has been widely reported and documented, but little research has been performed on rodent animals, e.g., mice. In this study, we report osteoinduction in a mouse model. Thirty mice were divided into two groups. BCP materials (Sample A) and control ceramics (Sample B) were implanted into the leg muscle, respectively. Five mice in each group were killed at 15, 30, and 45 d after surgery. Sample A and Sample B were harvested and used for hematoxylin and eosin (HE) staining, immunohistochemistry (IHC) staining, and Alizarin Red S staining to check bone formation in the biomaterials. Histological analysis showed that no bone tissue was formed 15 d after implantation (0/5) in either of the two groups. Newly-formed bone tissues were observed in Sample A at 30 d (5/5) and 45 d (5/5) after implantation; the average amounts of newly-formed bone tissues were approximately 5.2% and 8.6%, respectively. However, we did not see any bone tissue in Sample B until 45 d after implantation. Bone-related molecular makers such as bone morphogenesis protein-2 (BMP-2), collagen type I, and osteopontin were detected by IHC staining in Sample A 30 d after implantation. In addition, the newly-formed bone was also confirmed by Alizarin Red S staining. Because this is the report of osteoinduction in the rodent animal on which all the biotechnologies were available, our results may contribute to further mechanism research.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Cheng, L.J., Ye, F., Yang, R.N., Lu, X.F., Shi, Y.J., Li, L., Fan, H.S., Bu, H., 2010. Osteoinduction of hydroxyapatite/β-tricalcium phosphate bioceramics in mice with a fractured fibula. Acta Biomater., 6(4):1569-1574.

[2]Damien, C.J., Parsons, J.R., 1991. Bone graft and bone graft substitutes: a review of current technology and applications. J. Appl. Biomater., 2(3):187-208.

[3]Ducheyne, P., Cuckler, J.M., 1992. Bioactive ceramic prosthetic coatings. Clin. Orthop. Relat. Res., 276:102-114.

[4]Fan, H.S., Ikoma, T., Tanaka, J., Zhang, X.D., 2007. Surface structural biomimetics and the osteoinduction of calcium phosphate biomaterials. J. Nanosci. Nanetechnol., 7(3):808-813.

[5]Fellah, B.H., Josselin, N., Chappard, D., Weiss, P., Layrolle, P., 2007. Inflammatory reaction in rats muscle after implantation of biphasic calcium phosphate micro particles. J. Mater. Sci. Mater. Med., 18(2):287-294.

[6]Fellah, B.H., Gauthier, O., Weiss, P., Chappard, D., Layrolle, P., 2008. Osteogenicity of biphasic calcium phosphate ceramics and bone autograft in a goat model. Biomaterials, 29(9):1177-1188.

[7]Fellah, B.H., Delorme, B., Sohier, J., Magne, D., Hardouin, P., Layrolle, P., 2010. Macrophage and osteoblast responses to biphasic calcium phosphate microparticles. J. Biomed. Mater. Res. Part A, 93A(4):1588-1595.

[8]Green, J.P., Wojno, T.H., Wilson, M.W., Grossniklaus, H.E., 1995. Bone formation in hydroxyapatite orbital implants. Am. J. Ophthalmol., 120(5):681-682.

[9]Guo, H., Su, J., Wei, J., Kong, H., Liu, C., 2009. Biocompatibility and osteogenicity of degradable Ca-deficient hydroxyapatite scaffolds from calcium phosphate cement for bone tissue engineering. Acta Biomater., 5(1):268-278.

[10]Habibovic, P., Yuan, H., van der Valk, C.M., Meijer, G., van Blitterswijk, C.A., de Groot, K., 2005. 3D microenvironment as essential element for osteoinduction by biomaterials. Biomaterials, 26(17):3565-3575.

[11]Hennessy, K.M., Pollot, B.E., Clem, W.C., Phipps, M.C., Sawyer, A.A., Culpepper, B.K., Bellis, S.L., 2009. The effect of collagen I mimetic peptides on mesenchymal stem cell adhesion and differentiation, and on bone formation at hydroxyapatite surfaces. Biomaterials, 30(10):1898-1909.

[12]Kasten, P., Beyen, I., Niemeyer, P., Luginbuhl, R., Bohner, M., Richter, W., 2008. Porosity and pore size of β-tricalcium phosphate scaffold can influence protein production and osteogenic differentiation of human mesenchymal stem cells: an in vitro and in vivo study. Acta Biomater., 4(6):1904-1915.

[13]Li, Y.B., Klein, C.P., Zhang, X., de Groot, K., 1994. Formation of a bone apatite-like layer on the surface of porous hydroxyapatite ceramics. Biomaterials, 15(10):835-841.

[14]Nihouannen, D.L., Daculsi, G., Saffarzadeh, A., Gauthier, O., Delplace, S., Pilet, P., Layrolle, P., 2005. Ectopic bone formation by microporous calcium phosphate ceramic particles in sheep muscles. Bone, 36(6):1086-1093.

[15]Nihouannen, D.L., Saffarzadeh, A., Gauthier, O., Moreau, F., Pilet, P., Spaethe, R., Layrolle, P., Daculsi, G., 2008. Bone tissue formation in sheep muscles induced by a biphasic calcium phosphate ceramic and fibrin glue composite. J. Mater. Sci. Mater. Med., 19(2):667-675.

[16]Osborn, J.F., 1991. The Biological Profile of Hydroxyapatite Ceramic with Respect to the Cellular Dynamics of Animal and Human Soft Tissue and Mineralized Tissue under Unloaded and Loaded Conditions. In: Barbosa, M.A. (Ed.), Biomaterials Degradation. Elsevier Science Publishers, New York, p.185-225.

[17]Qu, S.X., Guo, X., Weng, J., Cheng, J.C., Feng, B., Yeung, H.Y., Zhang, X.D., 2004. Evaluation of the expression of collagen type I in porous calcium phosphate ceramics implanted in an extra-osseous site. Biomaterials, 25(4):659-667.

[18]Ripamonti, U., 1991a. Bone induction in nonhuman primates. An experimental study on the baboon. Clin. Orthop. Relat. Res., 269:284-294.

[19]Ripamonti, U., 1991b. The induction of bone in osteogenic composites of bone matrix and porous hydroxyapatite replicas: an experimental study on the baboon (Papio ursinus). J. Oral Maxillofac. Surg., 49(8):817-830.

[20]Ripamonti, U., 1991c. The morphogenesis of bone in replicas of porous hydroxyapatite obtained from conversion of calcium carbonate exoskeletons of coral. J. Bone Joint Surg. Am., 73(5):692-703.

[21]Ripamonti, U., 1996. Osteoinduction in porous hydroxyapatite implanted in heterotopic sites of different animal models. Biomaterials, 17(1):31-35.

[22]Ripamonti, U., Schnitzler, C.M., Cleaton-Jones, P.C., 1989. Bone induction in a composite allogeneic bone/alloplastic implant. J. Oral. Maxillofac. Surg., 47(9):963-969.

[23]Ripamonti, U., Jean, C., Lerato, K., Laura, R., 2009. The induction of bone formation by coral-derived calcium carbonate/hydroxyapatite constructs. Biomaterials, 30(7):1428-1439.

[24]Sontag, W., 1980. An automatic microspectrophotometric scanning method for the measurement of bone formation rates in vivo. Calcif. Tissue Int., 32(1):63-68.

[25]Toth, J.M., Lynch, K.L., Hackbarth, D.A., 1993. Ceramic-induced osteogenesis following subcutaneous implantation of calcium phosphates. Bioceramics, 6:9-13.

[26]Wang, C., Duan, Y., Markovic, B., Barbara, J., Howlett, C.R., Zhang, X., Zreiqat, H., 2004a. Phenotypic expression of bone-related genes in osteoblasts grown on calcium phosphate ceramics with different phase compositions. Biomaterials, 25(13):2507-2514.

[27]Wang, C., Duan, Y., Markovic, B., Barbara, J., Howlett, C.R., Zhang, X., Zreiqat, H., 2004b. Proliferation and bone-related gene expression of osteoblasts grown on hydroxyapatite ceramics sintered at different temperature. Biomaterials, 25(15):2949-2956.

[28]Wang, H., Li, Y., Zuo, Y., Li, J., Sansi, M., Cheng, L., 2007. Biocompatibility and osteogenesis of biomimetic nano-hydroxyapatite/polyamide composite scaffolds for bone tissue engineering. Biomaterials, 28(22):3338-3348.

[29]Wang, J.J., Ye, F., Cheng, L.J., Shi, Y.J., Bao, J., Sun, H.Q., Wang, W., Zhang, P., Bu, H., 2009. Osteogenic differentiation of mesenchymal stem cells promoted by overexpression of connective tissue growth factor overexpression of connective tissue growth factor. J. Zhejiang Univ.-Sci. B, 10(5):355-367.

[30]Yamasaki, H., Sakai, H., 1992. Osteogenic response to porous hydroxyapatite ceramics under the skin of dogs. Biomaterials, 13(5):308-312.

[31]Yang, Z.J., Yuan, H., Zou, P., Tong, W., Qu, S., Zhang, X.D., 1997. Osteogenic responses to extraskeletally implanted synthetic porous calcium phosphate ceramics: an early stage histomorphological study in dogs. J. Mater. Sci. Mater. Med., 8(11):697-701.

[32]Ye, F., Lu, X.F., Lu, B., Wang, J.J., Shi, Y.J., Zhang, L., Chen, J.Q., Li, Y.P., Bu, H., 2007. A long-term evaluation of osteoinductive HA/beta-TCP ceramics in vivo: 4.5 years study in pigs. J. Mater. Sci. Mater. Med., 18(11):2173-2178.

[33]Yuan, H., Zou, P., Yang, Z., Zhang, X., de Bruijn, J.D., de Groot, K., 1998a. Bone morphogenetic protein and ceramic-induced osteogenesis. J. Mater. Sci. Mater. Med., 9(12):717-721.

[34]Yuan, H., Yang, Z., Li, Y., Zhang, X., de Bruijn, J.D., de Groot, K., 1998b. Osteoinduction by calcium phosphate biomaterials. J. Mater. Sci. Mater. Med., 9(12):723-726.

[35]Yuan, H., Kurashina, K., de Bruijn, J.D., Li, Y., de Groot, K., Zhang, X., 1999. A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics. Biomaterials., 20(19):1799-1806.

[36]Yuan, H., Li, Y., de Bruijn, J.D., de Groot, K., Zhang, X., 2000. Tissue responses of calcium phosphate cement: a study in dogs. Biomaterials, 21(12):1283-1290.

[37]Yuan, H., de Bruijn, J.D., Li, Y., Feng, J., Yang, Z., de Groot, K., Zhang, X., 2001a. Bone formation induced by calcium phosphate ceramics in soft tissue of dogs: a comparative study between porous α-TCP and β-TCP. J. Mater. Sci. Mater. Med., 12(1):7-13.

[38]Yuan, H., Yang, Z., de Bruijn, J.D., de Groot, K., Zhang, X., 2001b. Material-dependent bone induction by calcium phosphate ceramics: a 2.5-year study in dog. Biomaterials, 22(19):2617-2623.

[39]Yuan, H., van den Doel, M., Li, S., van Blitterswijk, C.A., de Groot, K., de Bruijn, J.D., 2002. A comparison of the osteoinductive potential of two calcium phosphate ceramics implanted intramuscularly in goats. J. Mater. Sci.: Mater. Med., 13(12):1271-1275.

[40]Yuan, H., van Blitterswijk, C.A., de Groot, K., de Bruijn, J.D., 2006. A comparison of bone formation in biphasic calcium phosphate (BCP) and hydroxyapatite (HA) implanted in muscle and bone of dogs at different time periods. J. Biomed. Mater. Res. Part A, 78A(1):139-147.

[41]Zhang, X.D., Zhou, P., Wu, C., Qu, Y., Zhang, J., 1991. Bioceramics and the Human Body. Elsevier Applied Science, London, p.408.

[42]Zhang, X.D., Yuan, H., de Groot, K., 2000. Calcium Phosphate Biomaterials with Intrinsic Osteoinductivity. The 6th World Biomaterials Congress. Kamuela, Hawaii, USA, p.1-13.

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