Effect of gelatin on heparin regulation of cytokine release from hyaluronan-based hydrogels

被引:37
作者
Peattie, Robert A. [1 ]
Pike, Daniel B.
Yu, Bolan [2 ]
Cai, Shenshen [2 ]
Shu, Xiao Zheng [2 ]
Prestwich, Glenn D. [2 ]
Firpo, Matthew A. [3 ]
Fisher, Robert J. [4 ]
机构
[1] Tufts Univ, Ctr Sci & Technol, Dept Biomed Engn, Medford, MA 02155 USA
[2] Univ Utah, Dept Med Chem, Ctr Therapeut Biomat, Salt Lake City, UT 84112 USA
[3] Univ Utah, Sch Med, Dept Surg, Salt Lake City, UT USA
[4] MIT, Dept Chem Engn, Cambridge, MA 02139 USA
关键词
angiogenesis; controlled drug release; glycosaminoglycans; growth factors; cytokine;
D O I
10.1080/10717540802035442
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The hypothesis that incorporation of small amounts (0.3% w/w) of modified heparin in thiol-modified hyaluronan or HA and gelatin hydrogels would regulate release of cytokine growth factors (GFs) from those gels has been investigated in vitro. In addition, the physiologic response to gel implantation has been evaluated in vivo. Tests were performed with 6 GFs: basic fibroblast growth factor (bFGF), vascular endothelial growth factor ( VEGF), angiopoietin-1 (Ang-1), keratinocyte growth factor, platelet-derived growth factor-AA ( PDGF), and transforming growth factor-beta 1. Release profiles for all 6 over several weeks were well fit by first order exponential kinetics (R(2) > 0.9 for all cases). The most remarkable result of the experiment was a dramatic variation in the total mass ultimately released, which varied from as much as 90.2% of the initial load for bFGF to as little as 1.8% for PDGF, a 45-fold difference. Furthermore, gels containing either VEGF of Ang-1 produced twice the vascularization response in vivo as gels not containing a growth factor. Thus, those GFs maintained strong physiologic effectiveness.
引用
收藏
页码:389 / 397
页数:9
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