화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Macromolecular Research, Vol.24, No.9, 829-837, September, 2016
DOI10.1007/s13233-016-4112-7  Export Citation
Development of novel photopolymerizable hyaluronic acid/heparin-based hydrogel scaffolds with a controlled release of growth factors for enhanced bone regeneration
Min Soo Bae, Na Re Ko, Sang Jin Lee, Jung Bok Lee, Dong Nyoung Heo, Wook Byun, Byung-Joon Choi1, Hoon Bong Jeon2, Hee-Jae Jang3, Ji-Yoon Ahn3, Deok-Sang Hwang3, Bock-Young Jung4, †, and Il Keun Kwon†
  • Department of Dental Materials & Institute of Oral Biology, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea
  • 1Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea
  • 2Department of Biomedical Engineering, College of Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea
  • 3Department of Obstetrics & Gynecology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea
  • 4Department of Advanced General Dentistry, College of Dentistry, Yonsei University, 50 Yonsei-ro Seodaemun-gu, Seoul, 03722, Korea
E-mail:,
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.
Keywords:photopolymerization;hyaluronic acid;heparin;hydrogel;growth factor;bone tissue regeneration
  1. Bae JW, Go DH, Park KD, Lee SJ, Macromol. Res., 14(4), 461 (2006)
  2. Hong KH, Jeon YS, Chung DJ, Kim JH, Macromol. Res., 18(2), 204 (2010)
  3. Yun J, Oh AR, Im JS, Kim HI, Lee YS, Macromol. Res., 20(10), 1029 (2012)
  4. Lee WY, Chang YH, Yeh YC, Chen CH, Lin KM, Huang CC, Chang Y, Sung HW, Biomaterials, 30, 5505 (2009)
  5. Jeon O, Kang SW, Lim HW, Choi D, Kim DI, Lee SH, Chung JH, Kim BS, Biomaterials, 27, 1617 (2006)
  6. Orive G, De Castro M, Kong HJ, Hernandez RM, Ponce S, Mooney DJ, Pedraz JL, J. Control. Release, 135, 203 (2009)
  7. Park SA, Lee SH, Kim WD, Macromol. Res., 19(7), 694 (2011)
  8. Kim M, Kim YJ, Gwon K, Tae G, Macromol. Res., 20(3), 271 (2012)
  9. Choi SW, Moon SK, Chu JY, Lee HW, Park TJ, Kim JH, Macromol. Res., 20(5), 447 (2012)
  10. Kim DW, Lee CM, Kim NH, Lee SY, Lee MY, Choi ES, Park SA, Kim CG, Hwang H, Lim ST, Sohn MH, Jeong HJ, Macromol. Res., 22(3), 272 (2014)
  11. Hennink W, Van Nostrum CF, Adv. Drug Deliv. Rev., 64, 223 (2012)
  12. Van Tomme SR, Storm G, Hennink WE, Int. J. Pharm., 355, 1 (2008)
  13. Bae MS, Yang DH, Lee JB, Heo DN, Kwon YD, Youn IC, Choi K, Hong JH, Kim GT, Choi YS, Biomaterials, 32, 8161 (2011)
  14. Leach JB, Bivens KA, Patrick CW, Schmidt CE, Biotechnol. Bioeng., 82(5), 578 (2003)
  15. Pitarresi G, Casadei MA, Mandracchia D, Paolicelli P, Palumbo FS, Giammona G, J. Control. Release, 119, 328 (2007)
  16. Sakiyama-Elbert SE, Hubbell JA, J. Control. Release, 69, 149 (2000)
  17. Jeon O, Ryu SH, Chung JH, Kim BS, J. Control. Release, 105, 249 (2005)
  18. Zawko SA, Truong Q, Schmidt CE, J. Biomed. Mater. Res. A, 87, 1044 (2008)
  19. Obara K, Ishihara M, Ozeki Y, Ishizuka T, Hayashi T, Nakamura S, Saito Y, Yura H, Matsui T, Hattori H, J. Control. Release, 110, 79 (2005)
  20. Leach JB, Schmidt CE, Biomaterials, 26, 125 (2005)
  21. Tabata Y, Tissue Eng., 9, 5 (2003)
  22. Uebersax L, Merkle HP, Meinel L, Tissue Eng., 15, 263 (2009)
  23. Kogan G, Soltes L, Stern R, Gemeiner P, Biotechnol. Lett., 29(1), 17 (2007)
  24. Gerecht S, Burdick JA, Ferreira LS, Townsend SA, Langer R, Vunjak-Novakovic G, Proc. Natl. Acad. Sci., 104, 11298 (2007)
  25. Ossipov DA, Piskounova S, Varghese OP, Hilborn J, Biomacromolecules, 11(9), 2247 (2010)
  26. Yeom J, Bhang SH, Kim BS, Seo MS, Hwang EJ, Cho IH, Park JK, Hahn SK, Bioconjugate Chem., 21, 240 (2010)
  27. Maynard HD, Hubbell JA, Acta Biomater., 1, 451 (2005)
  28. Wang AY, Leong S, Liang YC, Huang RCC, Chen CS, Yu SM, Biomacromolecules, 9(10), 2929 (2008)
  29. Maxwell DJ, Hicks BC, Parsons S, Sakiyama-Elbert SE, Acta Biomater., 1, 101 (2005)
  30. Joung YK, Bae JW, Park KD, Expert Opin. Drug Deliv., 5, 1173 (2008)
  31. Wu J, Xu Y, Li Z, Yuan X, Wang P, Zhang X, Liu Y, Guan J, Guo Y, Li R, J. Mater. Sci. -Mater. Med., 22, 107 (2011)
  32. Tanihara M, Suzuki Y, Yamamoto E, Noguchi A, Mizushima Y, J. Biomed. Mater. Res., 56, 216 (2001)
  33. Nie T, Baldwin A, Yamaguchi N, Kiick KL, J. Control. Release, 122, 287 (2007)
  34. Nie T, Akins RE, Kiick KL, Acta Biomater., 5, 865 (2009)
  35. Lin CC, Boyer PD, Aimetti AA, Anseth KS, J. Control. Release, 142, 384 (2010)
  36. Yoon JJ, Chung HJ, Park TG, J. Biomed. Mater. Res. A, 83, 597 (2007)
  37. Jeon O, Powell C, Solorio LD, Krebs MD, Alsberg E, J. Control. Release, 154, 258 (2011)
  38. Yang HS, La WG, Bhang SH, Jeon JY, Lee JH, Kim BS, Tissue Eng. Part A, 16, 1225 (2010)
  39. Kim S, Kim JH, Jeon O, Kwon IC, Park K, Eur. J. Pharm. Biopharm., 71, 420 (2009)
  40. Sakiyama-Elbert SE, Hubbell JA, J. Control. Release, 65, 389 (2000)
  41. Ruppert R, Hoffmann E, Sebald W, Eur. J. Biochem., 237, 295 (1996)
  42. Zhao B, Katagiri T, Toyoda H, Takada T, Yanai T, Fukuda T, Chung UI, Koike T, Takaoka K, Kamijo R, J. Biol. Chem., 281, 23246 (2006)
  43. Ishibe T, Goto T, Kodama T, Miyazaki T, Kobayashi S, Takahashi T, Oral Surg. Oral Med. Oral Pathol., 108, 867 (2009)
  44. Takada T, Katagiri T, Ifuku M, Morimura N, Kobayashi M, Hasegawa K, Ogamo A, Kamijo R, J. Biol. Chem., 278, 43229 (2003)
  45. Elisseeff J, Anseth K, Sims D, McIntosh W, Randolph M, Langer R, Proc. Natl. Acad. Sci., 96, 3104 (1999)
  46. Capila I, Linhardt RJ, Angew. Chem.-Int. Edit., 41, 390 (2002)
  47. Rubinstein M, Colby RH, Dobrynin AV, Joanny JF, Macromolecules, 29(1), 398 (1996)
  48. Ilavsky M, Macromolecules, 15, 782 (1982)
  49. Okay O, Durmaz S, Polymer, 43(4), 1215 (2002)