Controlled Release Behavior of Bioactive Molecules from Photo-Reactive Hyaluronic Acid-Alginate Scaffolds

Hye Sung Nam; Jeongho An; Dong June Chung; Ji-Heung Kim; Chong-Pyoung Chung

Macromolecular Research, Vol.14, No.5, 530-538, October, 2006

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Controlled Release Behavior of Bioactive Molecules from Photo-Reactive Hyaluronic Acid-Alginate Scaffolds

Hye Sung Nam, Jeongho An , Dong June Chung^†, Ji-Heung Kim¹, and Chong-Pyoung Chung²

Dept. of Polymer Science and Engineering, SungKyunKwan University, Suwon 440-746, Korea
¹Dept. of Chemical Engineering, SungKyunKwan University, Suwon 440-746, Korea
²Intellectual Biointerface Engineering Center, Seoul National University, Seoul 110-749, Korea

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There are three important components in tissue engineering: the cells, signaling factors (cytokines and growth factors), and scaffolds. To obtain finely engineered tissue, all three components should perform their individual functions and be fully integrated with each other. For the past few years, we have studied the characteristics of photodimerizable HA (CHA)/alginate (CA) composite materials. CHA/CA complex hydrogels, which were irradiated under UV light and then treated with calcium ions, were found to have good biocompatibility, mechanical properties and water resistance for implantable tissue scaffolds. In this study, we introduced a cell growth factor (basic fibroblast growth factor; bFGF) into the CHA/CA scaffolds and studied its release behavior. We also introduced tetracycline hydrochloride and flurbiprofen into the same scaffolds as model activation factors and evaluated their release behaviors from the scaffolds. The drug release rate from the materials was influenced by various parameters, such as the degree of crosslinking, the crosslinker type, the physico-chemical properties of the drug, and the amount of the drug in the polymer. The results indicated that the negatively charged CHA/CA composite materials showed sustained release behavior and that HA has a particularly strong negative charge, making it attractive toward tetracycline hydrochloride and bFGF, but repulsive toward flurbiprofen.

Keywords:photodimerization;hyaluronic acid;sodium alginate;basic fibroblast growth factor (bFGF);biocompatible scaffold

[References]

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Frenkel S, Herskowitz M, Singh I, Acta Anat.(Basel), 143, 265 (1992)
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[2] Martin, Vunjak-Novakovic G, Yang J, Langer R, Freed LE, Exp. Cell Res., 253, 681 (1999)

[3] Landis WJ, Hodgens KJ, Arena J, Song MJ, McEwen BF, Microsc. Res. Techniq., 33, 192 (1996)

[4] Frenkel S, Herskowitz M, Singh I, Acta Anat.(Basel), 143, 265 (1992)

[5] Pitaru S, Kotev-Emeth S, Noff D, Kaffuler S, Savion N, J. Bone Miner. Res., 8, 929 (1993)

[6] Globus RK, Plouet J, Gospodarowicz D, Endocrinology, 124, 1530 (1989)

[7] Hauschka PV, Mavrakos AE, Iafrati MD, Doleman SE, Klagsbrun M, J. Biol. Chem., 261, 665 (1986)

[8] Mundy GR, Boyce B, Hughes D, Wright K, Bonewald L, Dallas S, Harris S, Ghash-choudhury N, Chen C, Dunstan C, Izbicka E, Yoneda T, Bone, 17, 71S (1995)

[9] Nagai H, Tsukuda R, Mayahara H, Bone, 16, 367 (1995)

[10] Van Wachem PB, Plantinga JA, Wissink MJ, Beernink R, Poot AA, Engbers GH, Beugeling T, Van Aken WG, Feijen J, Van Luyn MJ, J. Biomed. Mater. Res., 55, 368 (2001)

[11] Kawaguchi H, Nakamura K, Tabata Y, Ikada Y, Aoyama I, Anzai J, Nakamura T, Hiyama Y, Tamura M, J. Clin. Endocrinol. Metab., 86, 875 (2001)

[12] Tabata Y, Nagano A, Muniruzzaman M, Ikada Y, Biomaterials, 19, 1781 (1998)

[13] Radomsky ML, Swain L, Aufdemorte T, Fox C, Poser J, Transactions of the 43rd Annual Meeting, The Orthopaedic Research Society, 9 (1997)

[14] Larsen NE, Balazs EA, Adv. Drug Deliv. Rev., 7, 279 (1991)

[15] Morgelin M, Heinegard D, Engel J, Paulsson M, Biophys. Chem., 50, 113 (1994)

[16] Chung DJ, Matsuda T, J. Ind. Eng. Chem., 4(4), 340 (1998)

[17] Della Valle F, Romeo A, US Patent 5,336,767 (1994)

[18] Pelletier S, Hubert P, Lapicque F, Payan E, Dellacherie E, Carbohydr. Polym., 43, 343 (2000)

[19] Tomihata K, Ikada Y, Biomaterials, 18, 189 (1997)

[20] Bulpitt P, Aeschlimann D, J. Biomed. Mater. Res., 47, 152 (1999)

[21] Al-Musa S, Abu Fara D, Badwan AA, J. Control. Release, 57, 223 (1999)

[22] Eiselt P, Yeh J, Latvala RK, Shea LD, Mooney DJ, Biomaterials, 21, 1921 (2000)

[23] Cuo CK, Ma PX, Biomaterials, 22, 511 (2001)

[24] Kang HW, Tabata Y, Ikada Y, Biomaterials, 20, 1339 (1999)

[25] Nam HS, Kim JH, An JH, Chung DJ, Polym.(Korea), 25(4), 476 (2001)

[26] Park YJ, Lee YM, Park SN, Lee JY, Ku Y, Chung CP, Lee SJ, J. Biomed. Mater. Res., 51, 391 (2000)

[27] Cho CS, Ha JH, Kim SH, Han SY, Kwon OK, Sung YK, J. Appl. Polym. Sci., 60(2), 161 (1996)

[28] Gamisans F, Lacoulonche F, Chauvet A, Espina M, Garcia ML, Egea EA, Int. J. Pharm., 179, 37 (1999)

[29] Kang SJ, Nam HS, An JH, Bae JY, Chung DJ, Biomater. Res., 5, 10 (2002)