We developed a bone-regenerative scaffold based on systematic combination of porous organic-inorganic hybrid scaffolds and recombinant human parathyroid hormone (rhPTH). The hybrid scaffold was fabricated by immobilization of polyphosphate-functionalized nano-hydroxyapatite (PP-n-HAp) on the surface of porous poly(L-lactic acid) (PLLA) scaffolds, which was followed by rhPTH loading on the polyphosphates of n-HAp surfaces. The surface polyphosphate functionalities of PP-n-HAp enabled the stable chemical immobilization of n-HAp on the amine-treated pore surface of the PLGA scaffolds. rhPTH with a positive charge was bound at a high efficiency of 98.1~99.5% onto the anionic polyphosphates of PP-n-HAp immobilized on PLLA surfaces and was sustainably released for up to 50 days. The release rate was manipulated by adjusting the amount of loaded rhPTH, and the release data were moderately fitted to the Higuchi’s diffusion model. Four types of scaffolds were tested in rabbit calvarias models (PLLA only, PP-n-HAp-PLLA, rhPTH (2 µg) loaded PP-n-HAp-PLLA, and rhPTH (10 µg) loaded PP-n-HAp-PLLA). After 5 weeks, rhPTH-loaded PP-n-HAp-PLLA (2 and 10 µg of rhPTH) displayed higher bone growth than the control (PLLA only) group. Nano-HAp and sustained release of rhPTH might be synergistically able to enhance the bone healing in the animal model.
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R. M. Neer, C. D. Arnaud, J. R. Zanchetta, R. Prince, G. A. Gaich, J. Y. Reginster, A. B. Hodsman, E. F. Eriksen, S. Ish-Shalom, H. K. Genant, O. Wang, D. Mellström, E. S. Oefjord, E. Marcinowska-Suchowierska, J. Salmi, H. Mulder, J. Halse, A. Z. Sawicki, and B. H. Mitlak, N. Engl. J. Med., 344, 1434 (2001).
S. L. Greenspan, H. G. Bone, M. P. Ettinger, D. A. Hanley, R. Lindsay, J. R. Zanchetta, C. M. Blosch, A. L. Mathisen, S. A. Morris, and T. B. Marriott, Ann. Intern. Med., 146, 326 (2007).
T. Manabe, S. Mori, T. Mashiba, Y. Kaji, K. Iwata, S. Komatsubara, A. Seki, Y.-X. Sun, and T. Yamamoto, Bone, 40, 1475 (2007).
A. B. Hodsman, M. Kisiel, J. D. Adachi, L. J. Fraher, and P. H. Watson, Bone, 27, 311 (2000).
Y. Jiang, J. J. Zhao, B. H. Mitlak, O. Wang, H. K. Genant, and E. F. Eriksen. J. Bone Miner. Res., 18, 1932 (2003).
K. T. Brixen, P. M. Christensen, C. Ejersted, and B. L. Langdahl, Basic Clin. Pharmacol. Toxicol., 94, 260 (2004).
P. Aggarwal and A. Zavras, Oral Dis., 18, 48 (2012).
H. L. Chan and L. K. McCauley, J. Dent. Res., 92, 18 (2013).
T. J. Wronski and C. F. Yen, Bone, 15, 51 (1994).
M. Gunness-Hey and J. M. Hock, Metab. Bone Dis. Res., 5, 171 (1984).
J. M. Hock, M. Centrella, and E. Canalis, Endocrinology, 122, 2899 (1988).
H. Oxlund, C. Ejersted, T. T. Andreassen, O. Torring, and M. H. Nilsson, Calcif. Tissue Int., 53, 394 (1993).
T. J. Wronski, C. F. Yen, H. Qi, and L. M. Dann, Endocrinology, 132, 823 (1993).
Y. Liu, Y. Lu, X. Tian, G. Cui, Y. Zhao, Q. Yang, S. Yu, G. Xing, and B. Zhang, Biomaterials, 30, 6276 (2009).
S. Fu, P. Ni, B. Wang, B. Chu, J. Peng, L. Zheng, X. Zhao, F. Luo, Y. Wei, and Z. Qian, Biomaterials, 33, 8363 (2012).
K. Kim, D. Dean, A. Lu, A. G. Mikos, and J. P. Fisher, Acta Biomater., 7, 1249 (2011).
H. Shen, X. Hu, F. Yang, J. Bei, and S. Wang, Acta Biomater., 6, 455 (2010).
A. Ronca, L. Ambrosio, and D. W. Grjpma, Acta Biomater., 9, 5989 (2013).
N. Ribeiro, S. R. Sousa, and F. J. Monteiro, J. Colloid Interface Sci., 351, 398 (2010).
S. E. Kim, H. W. Choi, H. J. Lee, J. H. Chang, J. Choi, K, J. Kim, H. J. Lim, Y. J. Jun, and S. C. Lee, J. Mater. Chem., 18, 4994 (2008).
B. J. Jeon, S. Y. Jeong, A. N. Koo, B. C. Kim, Y. S. Hwang, and S. C. Lee, Macromol. Res., 20, 715 (2012).
Z. Song, Z. Yin, C. Li, Z. Yang, C. Ning, D. Zhou, R. Wang, Y. Xu, and J. Qiu, Mater. Sci. Eng. C, 32, 1032 (2012).
F. J. Hua, G. E. Kim, J. D. Lee, Y. K. Son, and D. S. Lee, J. Biomed. Mater. Res., 63, 161 (2002).
W. Chunxiao, L. Jingjing, X. Yire, D. Min, W. Zhaohui, Q. Gaofu, S. Xiangchun, W. Xuejun, W. Jie, and L. Taiming, Regul. Pept., 141, 35 (2007).
B. M. Medi and J. Singh, Int. J. Pharm., 263, 25 (2003).
H. J. Lee, A. N. Koo, S. W. Lee, M. H. Lee, and S. C. Lee, J. Control. Release, 170, 198 (2013).
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Koo, A.N., Ohe, J., Lee, D. et al. Bone-regenerative activity of parathyroid hormone-releasing nano-hydroxyapatite/poly(L-lactic acid) hybrid scaffolds. Macromol. Res. 23, 1168–1173 (2015). https://doi.org/10.1007/s13233-015-3157-3
- parathyroid hormone
- sustained release
- poly(L-lactic acid)
- surface immobilization