Effect of gelatin on heparin regulation of cytokine release from hyaluronan-based hydrogels.
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.
Peattie
Robert A
RA
Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155, USA. robert.peattie@tufts.edu
Pike
Daniel B
DB
Yu
Bolan
B
Cai
Shenshen
S
Shu
Xiao Zheng
XZ
Prestwich
Glenn D
GD
Firpo
Matthew A
MA
Fisher
Robert J
RJ
D043925:Angiogenesis Inducing Agents / Q000737:chemistry / Q000378:metabolism; D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D002417:Cattle; D016207:Cytokines / Q000378:metabolism*; D004343:Drug Implants / Q000737:chemistry / Q000378:metabolism; D004423:Ear / Q000098:blood supply; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism; D005780:Gelatin / Q000737:chemistry*; D006025:Glycosaminoglycans / Q000737:chemistry; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D016207:Cytokines; D004343:Drug Implants; D006025:Glycosaminoglycans; D020100:Hydrogels; D010982:Platelet-Derived Growth Factor; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D051523:Fibroblast Growth Factor 7; D005780:Gelatin; D006820:Hyaluronic Acid; D006493:Heparin