Osteoblastic Differentiation of Functionalized Biphasic Hydroxyapatite and b-Tricalcium Phosphate with Recombinant Human Growth and Differentiation (rhGDF-5)

Joo-Young Ohe; Byung-Joon Choi; Junho Jung; Jeewan Chun; Youngjae Yoon; Yong-Dae Kwon

Macromolecular Research, Vol.26, No.11, 1011-1018, November, 2018

DOI10.1007/s13233-018-6142-9 Export Citation

Osteoblastic Differentiation of Functionalized Biphasic Hydroxyapatite and b-Tricalcium Phosphate with Recombinant Human Growth and Differentiation (rhGDF-5)

Joo-Young Ohe¹, Byung-Joon Choi¹, Junho Jung¹, Jeewan Chun², Youngjae Yoon², and Yong-Dae Kwon^{1, 2, †}

¹Department of Oral & Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Seoul 02453, Korea
²Department of Oral & Maxillofacial Surgery, Graduate School, Kyung Hee University, Seoul 02453, Korea

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The purpose of this research was to examine the effect of biphasic hydroxyapatite and b-tricalcium phosphate (HAp-bTCP) immobilized GDF-5 to assess the hypothesis that osteoblast is enhanced and bone formation is promoted when compared to biphasic HAp-bTCP in vitro and in vivo. First, we characterized the release profiles from HAp-bTCP and tested their cell viability, differentiation. After that, we loaded GDF-5 to HAp-bTCP. In the animal study, 4 full thickness critical-size calvarial defects were prepared in a total of 16 male rabbits. The cranial defects were filled with HAP-bTCp, or heparized HAP-bTCP. At 5 and 10 weeks, dissected specimens were processed for histological and histochemical analysis. GDF-5 was considered to be released in a sustained mode from HAp-bTCP. In vitro results provided that the proliferation and differentiation of MG-63 cells to HAp-bTCP-GDF-5 was higher than that of the control group. In addition, in vivo animal studies showed that HAp-bTCP-GDF- 5 has a significant improvement to bone formation. HAp-bTCP-GDF-5 is thought to be an excellent biomaterial that delivers osteogenic differentiation factors such as GDF-5, and GDF-5 can be possibly useful as an effective alternative to avail new bone formation.

Keywords:GDF-5;HAp-bTCP;HAp-bTCP-GDF-5;osteogenic differentiation

[References]

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[2] Urist MR, Science, 150, 893 (1965)

[3] Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA, Science, 242, 1528 (1988)

[4] Reddi AH, Nat. Biotechnol., 16, 247 (1998)

[5] Hughes FJ, Turner W, Belibasakis G, Martuscelli G, Periodontol. 2000, 41, 48 (2006)

[6] Boyne PJ, Marx RE, Nevins M, Triplett G, Lazaro E, Lilly LC, Alder M, Nummikoski P, Int. J. Periodontics Restorative Dent., 17, 11 (1997)

[7] Howell TH, Fiorellini J, Jones A, Alder M, Nummikoski P, Lazaro M, Lilly L, Cochran D, Int. J. Periodontics Restorative Dent., 17, 124 (1997)

[8] Nishitoh H, Ichijo H, Kimura M, Matsumoto T, Makishima F, Yamaguchi A, Yamashita H, Enomoto S, Miyazono K, J. Biol. Chem., 271, 21345 (1996)

[9] Chang SC, Hoang B, Thomas JT, Vukicevic S, Luyten FP, Ryba NJ, Kozak CA, Reddi AH, Moos M, J. Biol. Chem., 269, 28227 (1994)

[10] Morotome Y, Goseki-Sone M, Ishikawa I, Oida S, Biochem. Biophys. Res. Commun., 244, 85 (1998)

[11] Buxton P, Edwards C, Archer CW, Francis-West P, J. Bone Joint Surg.-Am. Vol., 83-A Su, S23 (2011)

[12] Shen FH, Zeng Q, Lv Q, Choi L, Balian G, Li X, Laurencin CT, Spine J., 6, 615 (2006)

[13] Zeng Q, Li X, Beck G, Balian G, Shen FH, Bone, 40, 374 (2007)

[14] Gruber RM, Ludwig A, Merten HA, Achilles M, Poehling S, Schliephake H, Clin. Oral Implants Res., 19, 522 (2008)

[15] Moon HJ, Yun YP, Han CW, Kim MS, Kim SE, Bae MS, Kim GT, Choi YS, Hwang EH, Lee JW, Lee JM, Lee CH, Kim DS, Kwon IK, Biochem. Biophys. Res. Commun., 413(2), 194 (2011)

[16] Kim SE, Song SH, Yun YP, Choi BJ, Kwon IK, Bae MS, Moon HJ, Kwon YD, Biomaterials, 32, 366 (2011)

[17] Sasisekharan R, Ernst S, Venkataraman G, Angiogenesis, 1, 45 (1997)

[18] Bryant SR, Int. J. Prosthodont, 11, 470 (1998)

[19] Porter JA, von Fraunhofer JA, Gen. Dent., 53, 423 (2005)

[20] Cricchio G, Lundgren S, Clin. Implant Dent. Relat. Res., 5, 161 (2003)

[21] Jung RE, Thoma DS, Hammerle CH, J. Clin. Periodontol., 35, 255 (2008)

[22] Gruber R, Mayer C, Schulz W, Graninger W, Peterlik M, Watzek G, Luyten FP, Erlacher L, Cytokine, 12, 1630 (2000)

[23] Puleo DA, J. Cell. Physiol., 173, 93 (1997)

[24] Yamaguchi A, Ishizuya T, Kintou N, Wada Y, Katagiri T, Wozney JM, Rosen V, Yoshiki S, Biochem. Biophys. Res. Commun., 220, 366 (1996)

[25] Koch FP, Weinbach C, Hustert E, Al-Nawas B, Wagner W, Int. J. Periodontics Restorative Dent., 32, 285 (2012)

[26] Koch FP, Becker J, Terheyden H, Capsius B, Wagner W, Trial RGMC, Clin. Oral Implants Res., 21, 1301 (2010)

[27] Kuniyasu H, Yukito H, Yajima A, Ochi M, Kagami H, Shigino T, Sakaguchi K, Pohl J, in 3rd World Congress of Osseointegration, Italy, 2001.

[28] Stavropoulos A, Becker J, Capsius B, Acil Y, Wagner W, Terheyden H, J. Clin. Periodontol., 38, 966 (2011)

[29] Magit DP, Maak T, Trioano N, Raphael B, Hamouria Q, Polzhofer G, Drespe I, Albert TJ, Grauer JN, Spine, 31, 2180 (2006)