Abstract
In this study, the effect of novel BMP-2-loaded photo-cured hydrogels on in vitro and in vivo osteogenesis were explored. The well-defined HA-heparin hydrogel was prepared by a photopolymerization of aminoethyl methacrylate (AEMA) grafted hyaluronic acid (HA) and AEMA-grafted heparin. Subsequently, the resulting hydrogels contained BMP-2 at different concentrations. First, a series of BMP-2-loaded hydrogels were characterized to determine their mechanical properties and release profiles. The results from rheology, swelling ratio, and release kinetics suggest that BMP-2 contained HA-g-Hhep gel (B/HA-g-Hhep gel) had sustained release during 4 weeks with minimal initial burst. Furthermore, the released BMP-2 maintained its biological activity. MTT and live/dead assays showed that the B/HA-g-Hhep gel had good biocompatibility to be used as a scaffold for bone regeneration. In vivo studies of B/HA-g-Hhep gel exhibited significantly enhanced osteogenesis, compared with other types of HA-heparin hydrogels. These excellent results indicated that B/HA-g-Hhep gel has a great potential for a controlled release of growth factor, leading to a good bone regeneration.
Similar content being viewed by others
References
J. W. Bae, D. H. Go, K. D. Park, and S. J. Lee, Macromol. Res., 14, 461 (2006).
K. H. Hong, Y.-S. Jeon, D. J. Chung, and J.-H. Kim, Macromol. Res., 18, 204 (2010).
J. Yun, A.-R. Oh, J. S. Im, H.-I. Kim, and Y.-S. Lee, Macromol. Res., 20, 1029 (2012).
W.-Y. Lee, Y.-H. Chang, Y.-C. Yeh, C.-H. Chen, K. M. Lin, C.-C. Huang, Y. Chang, and H.-W. Sung, Biomaterials, 30, 5505 (2009).
O. Jeon, S.-W. Kang, H.-W. Lim, D. Choi, D.-I. Kim, S. H. Lee, J. H. Chung, and B.-S. Kim, Biomaterials, 27, 1617 (2006).
G. Orive, M. De Castro, H.-J. Kong, R. M. Hernández, S. Ponce, D. J. Mooney, and J. L. Pedraz, J. Control. Release, 135, 203 (2009).
S. A. Park, S. H. Lee, and W. Kim, Macromol. Res., 19, 694 (2011).
M. Kim, Y.-J. Kim, K. Gwon, and G. Tae, Macromol. Res., 20, 271 (2012).
S.-W. Choi, S.-K. Moon, J.-Y. Chu, H.-W. Lee, T.-J. Park, and J.-H. Kim, Macromol. Res., 20, 447 (2012).
D.-W. Kim, C.-M. Lee, N.-H. Kim, S. Y. Lee, M. Y. Lee, E. S. Choi, S.-A. Park, C. G. Kim, H. Hwang, and S. T. Lim, Macromol. Res., 22, 272 (2014).
W. Hennink and C. F. Van Nostrum, Adv. Drug Deliv. Rev., 64, 223 (2012).
S. R. Van Tomme, G. Storm, and W. E. Hennink, Int. J. Pharm., 355, 1 (2008).
M. S. Bae, D. H. Yang, J. B. Lee, D. N. Heo, Y.-D. Kwon, I. C. Youn, K. Choi, J. H. Hong, G. T. Kim, and Y. S. Choi, Biomaterials, 32, 8161 (2011).
J. B. Leach, K. A. Bivens, C. W. Patrick, and C. E. Schmidt, Biotechnol. Bioeng., 82, 578 (2003).
G. Pitarresi, M. A. Casadei, D. Mandracchia, P. Paolicelli, F. S. Palumbo, and G. Giammona, J. Control. Release, 119, 328 (2007).
S. E. Sakiyama-Elbert and J. A. Hubbell, J. Control. Release, 69, 149 (2000).
O. Jeon, S. H. Ryu, J. H. Chung, and B.-S. Kim, J. Control. Release, 105, 249 (2005).
S. A. Zawko, Q. Truong, and C. E. Schmidt, J. Biomed. Mater. Res. Part A, 87, 1044 (2008).
K. Obara, M. Ishihara, Y. Ozeki, T. Ishizuka, T. Hayashi, S. Nakamura, Y. Saito, H. Yura, T. Matsui, and H. Hattori, J. Control. Release, 110, 79 (2005).
J. B. Leach and C. E. Schmidt, Biomaterials, 26, 125 (2005).
Y. Tabata, Tissue Eng., 9, 5 (2003).
L. Uebersax, H. P. Merkle, and L. Meinel, Tissue Eng. Part B: Rev., 15, 263 (2009).
G. Kogan, L. Šoltés, R. Stern, and P. Gemeiner, Biotechnol. Lett., 29, 17 (2007).
S. Gerecht, J. A. Burdick, L. S. Ferreira, S. A. Townsend, R. Langer, and G. Vunjak-Novakovic, Proc. Natl. Acad. Sci., 104, 11298 (2007).
D. A. Ossipov, S. Piskounova, O. P. Varghese, and J. N. Hilborn, Biomacromolecules, 11, 2247 (2010).
J. Yeom, S. H. Bhang, B.-S. Kim, M. S. Seo, E. J. Hwang, I. H. Cho, J. K. Park, and S. K. Hahn, Bioconjug. Chem., 21, 240 (2010).
H. D. Maynard and J. A. Hubbell, Acta Biomater., 1, 451 (2005).
A. Y. Wang, S. Leong, Y.-C. Liang, R. C. C. Huang, C. S. Chen, and S. M. Yu, Biomacromolecules, 9, 2929 (2008).
D. J. Maxwell, B. C. Hicks, S. Parsons, and S. E. Sakiyama-Elbert, Acta Biomater., 1, 101 (2005).
Y. K. Joung, J. W. Bae, and K. D. Park, Expert Opin. Drug Deliv., 5, 1173 (2008).
J. Wu, Y. Xu, Z. Li, X. Yuan, P. Wang, X. Zhang, Y. Liu, J. Guan, Y. Guo, and R. Li, J. Mater. Sci. Mater. Med., 22, 107 (2011).
M. Tanihara, Y. Suzuki, E. Yamamoto, A. Noguchi, and Y. Mizushima, J. Biomed. Mater. Res., 56, 216 (2001).
T. Nie, A. Baldwin, N. Yamaguchi, and K. L. Kiick, J. Control. Release, 122, 287 (2007).
T. Nie, R. E. Akins, and K. L. Kiick, Acta Biomater., 5, 865 (2009).
C.-C. Lin, P. D. Boyer, A. A. Aimetti, and K. S. Anseth, J. Control. Release, 142, 384 (2010).
J. J. Yoon, H. J. Chung, and T. G. Park, J. Biomed. Mater. Res. Part A, 83, 597 (2007).
O. Jeon, C. Powell, L. D. Solorio, M. D. Krebs, and E. Alsberg, J. Control. Release, 154, 258 (2011).
H. S. Yang, W.-G. La, S. H. Bhang, J.-Y. Jeon, J. H. Lee, and B.-S. Kim, Tissue Eng. Part A, 16, 1225 (2010).
S. Kim, J.-H. Kim, O. Jeon, I. C. Kwon, and K. Park, Eur. J. Pharm. Biopharm., 71, 420 (2009).
S. E. Sakiyama-Elbert and J. A. Hubbell, J. Control. Release, 65, 389 (2000).
R. Ruppert, E. Hoffmann, and W. Sebald, Eur. J. Biochem., 237, 295 (1996).
B. Zhao, T. Katagiri, H. Toyoda, T. Takada, T. Yanai, T. Fukuda, U.-i. Chung, T. Koike, K. Takaoka, and R. Kamijo, J. Biol. Chem., 281, 23246 (2006).
T. Ishibe, T. Goto, T. Kodama, T. Miyazaki, S. Kobayashi, and T. Takahashi, Oral Surg. Oral Med. Oral Pathol., 108, 867 (2009).
T. Takada, T. Katagiri, M. Ifuku, N. Morimura, M. Kobayashi, K. Hasegawa, A. Ogamo, and R. Kamijo, J. Biol. Chem., 278, 43229 (2003).
J. Elisseeff, K. Anseth, D. Sims, W. McIntosh, M. Randolph, and R. Langer, Proc. Natl. Acad. Sci., 96, 3104 (1999).
I. Capila and R. J. Linhardt, Angew. Chem. Int. Ed., 41, 390 (2002).
M. Rubinstein, R. H. Colby, A. V. Dobrynin, and J.-F. Joanny, Macromolecules, 29, 398 (1996).
M. Ilavsky, Macromolecules, 15, 782 (1982).
O. Okay and S. Durmaz, Polymer, 43, 1215 (2002).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Bae, M.S., Ko, N.R., Lee, S.J. et al. Development of novel photopolymerizable hyaluronic acid/heparin-based hydrogel scaffolds with a controlled release of growth factors for enhanced bone regeneration. Macromol. Res. 24, 829–837 (2016). https://doi.org/10.1007/s13233-016-4112-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13233-016-4112-7