Biohybrid Networks of Selectively Desulfated Glycosaminoglycans for Tunable Growth Factor Delivery

被引:39
作者
Zieris, Andrea [1 ]
Dockhorn, Ron [1 ,2 ]
Roehrich, Anika [3 ]
Zimmermann, Ralf [1 ]
Mueller, Martin [1 ]
Welzel, Petra B. [1 ]
Tsurkan, Mikhail V. [1 ]
Sommer, Jens-Uwe [1 ,2 ]
Freudenberg, Uwe [1 ,4 ]
Werner, Carsten [1 ,4 ]
机构
[1] Leibniz Inst Polymer Res Dresden, D-01069 Dresden, Germany
[2] Tech Univ Dresden, Inst Theoret Phys, D-01069 Dresden, Germany
[3] Tech Univ Dresden, CUBE Ctr Mol Bioengn B, D-01307 Dresden, Germany
[4] Tech Univ Dresden, Ctr Regenerat Therapies Dresden, D-01307 Dresden, Germany
关键词
COUNTERION-CONDENSATION THEORY; N-HYDROXYSUCCINIMIDE; CONTROLLED-RELEASE; POTENTIOMETRIC TITRATIONS; CHEMICAL-MODIFICATIONS; HEPARIN DERIVATIVES; SUSTAINED-RELEASE; HYDROGELS; BINDING; SYSTEMS;
D O I
10.1021/bm5012294
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Sulfation patterns of glycosaminoglycans (GAG) govern the electrostatic complexation of biomolecules and thus allow for modulating the release profiles of growth factors from GAG-based hydrogels. To explore options related to this, selectively desulfated heparin derivatives were prepared, thoroughly characterized, and covalently converted with star-shaped poly(ethylene glycol) into binary polymer networks. The impact of the GAG sulfation pattern on the network characteristics of the obtained hydrogels was theoretically evaluated by mean field methods and experimentally analyzed by rheometry and swelling measurements. Sulfation-dependent differences of reactivity and miscibility of the heparin derivatives were shown to determine network formation. A theory-based design concept for customizing growth factor affinity and physical characteristics was introduced and validated by quantifying the release of fibroblast growth factor 2 from a set of biohybrid gels. The resulting new class of cell-instructive polymer matrices with tunable GAG sulfation will be instrumental for multiple applications in biotechnology and medicine.
引用
收藏
页码:4439 / 4446
页数:8
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