Injectable glycosaminoglycan hydrogels for controlled release of human basic fibroblast growth factor

被引:343
作者
Cai, SS [1 ]
Liu, YC [1 ]
Shu, XZ [1 ]
Prestwich, GD [1 ]
机构
[1] Univ Utah, Dept Med Chem, Salt Lake City, UT 84108 USA
关键词
heparin; hyaluronan; chondroitin sulfate; wound healing; neovascularization; synthetic extracellular matrix;
D O I
10.1016/j.biomaterials.2005.03.012
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Synthetic hydrogel mimics of the extracellular matrix (ECM) were created by crosslinking a thiol-modified analog of heparin with thiol-modified hyaluronan (HA) or chondroitin sulfate (CS) with poly(ethylene glycol) diacrylate (PEGDA). The covalently bound heparin provided a crosslinkable analog of a heparan sulfate proteoglycan, thus providing a multivalent biomaterial capable of controlled release of basic fibroblast growth factor (bFGF). Hydrogels contained > 97% water and formed rapidly in < 10 min. With as little as 1% (w/w) covalently bound heparin (relative to total glycosaminoglycan content), the rate of release of bFGF in vitro was substantially reduced. Total bFGF released increased with lower percentages of heparin; essentially quantitative release of bFGF was observed from heparin-free hydrogels. Moreover, the hydrogel-released bFGF retained 55% of its biological activity for up to 28 days as determined by a cell proliferation assay. Finally, when these hydrogels were implanted into subcutaneous pockets in Balb/c mice, neovascularization increased dramatically with HA and CS hydrogels that contained both bFGF and crosslinked heparin. In contrast, hydrogels lacking bFGF or crosslinked heparin showed little increase in neovascularization. Thus, covalently linked, heparin-containing glycosaminoglycan hydrogels that can be injected and crosslinked in situ constitute highly promising new materials for controlled release of heparin-binding growth factors in vivo. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:6054 / 6067
页数:14
相关论文
共 54 条
[1]   In situ forming degradable networks and their application in tissue engineering and drug delivery [J].
Anseth, KS ;
Metters, AT ;
Bryant, SJ ;
Martens, PJ ;
Elisseeff, JH ;
Bowman, CN .
JOURNAL OF CONTROLLED RELEASE, 2002, 78 (1-3) :199-209
[2]   THIOLATION OF PROTEINS [J].
BENESCH, R ;
BENESCH, RE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1958, 44 (09) :848-853
[3]   Delivery of osteoinductive growth factors from degradable PEG hydrogels influences osteoblast differentiation and mineralization [J].
Burdick, JA ;
Mason, MN ;
Hinman, AD ;
Thorne, K ;
Anseth, KS .
JOURNAL OF CONTROLLED RELEASE, 2002, 83 (01) :53-63
[4]   A MODIFICATION OF ELLMAN PROCEDURE FOR ESTIMATION OF PROTEIN SULFHYDRYL GROUPS [J].
BUTTERWORTH, PH ;
BAUM, H ;
PORTER, JW .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1967, 118 (03) :716-+
[5]   Release of recombinant human interleukin-2 from dextran-based hydrogels [J].
Cadée, JA ;
de Groot, CJ ;
Jiskoot, W ;
den Otter, W ;
Hennink, WE .
JOURNAL OF CONTROLLED RELEASE, 2002, 78 (1-3) :1-13
[6]   Development of poly-(D,L-lactide-coglycolide) microsphere formulations containing recombinant human vascular endothelial growth factor to promote local angiogenesis [J].
Cleland, JL ;
Duenas, ET ;
Park, A ;
Daugherty, A ;
Kahn, J ;
Kowalski, J ;
Cuthbertson, A .
JOURNAL OF CONTROLLED RELEASE, 2001, 72 (1-3) :13-24
[7]   In vitro assessment of the biological activity of basic fibroblast growth factor released from various polymers and biomatrices [J].
Davies, MJ ;
Mitchell, CA ;
Maley, MAL ;
Grounds, MD ;
Harvey, AR ;
Plant, GW ;
Wood, DJ ;
Hong, Y ;
Chirila, TV .
JOURNAL OF BIOMATERIALS APPLICATIONS, 1997, 12 (01) :31-56
[8]   CONTROLLED AND MODULATED RELEASE OF BASIC FIBROBLAST GROWTH-FACTOR [J].
EDELMAN, ER ;
MATHIOWITZ, E ;
LANGER, R ;
KLAGSBRUN, M .
BIOMATERIALS, 1991, 12 (07) :619-626
[9]  
FOLKMAN J, 1992, ADV EXP MED BIOL, V313, P355
[10]   Chondroitin sulfate hydrogel and wound healing in rabbit maxillary sinus mucosa [J].
Gilbert, ME ;
Kirker, KR ;
Gray, SD ;
Ward, D ;
Szakacs, JG ;
Prestwich, GD ;
Orlandi, RR .
LARYNGOSCOPE, 2004, 114 (08) :1406-1409