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Tuning the Local Availability of VEGF within Glycosaminoglycan‐Based Hydrogels to Modulate Vascular Endothelial Cell Morphogenesis
Author(s) -
Limasale Yanuar Dwi Putra,
Atallah Passant,
Werner Carsten,
Freudenberg Uwe,
Zimmermann Ralf
Publication year - 2020
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202000068
Subject(s) - self healing hydrogels , glycosaminoglycan , sulfation , materials science , tissue engineering , heparin , growth factor , biophysics , vascular endothelial growth factor , ethylene glycol , extracellular matrix , chemistry , biomedical engineering , biochemistry , vegf receptors , biology , polymer chemistry , organic chemistry , receptor , medicine , cancer research
Incorporation of sulfated glycosaminoglycans (GAGs) into cell‐instructive polymer networks is shown to be instrumental in controlling the diffusivity and activity of growth factors. However, a subtle balance between local retention and release of the factors is needed to effectively direct cell fate decisions. To quantitatively unravel material characteristics governing these key features, the GAG content and the GAG sulfation pattern of star‐shaped poly(ethylene glycol) (starPEG)–GAG hydrogels are herein tuned to control the local availability and bioactivity of GAG‐affine vascular endothelial growth factor (VEGF165). Hydrogels containing varying concentrations of heparin or heparin derivatives with different sulfation pattern are prepared and thoroughly characterized for swelling, mechanical properties, and growth factor transport. Mathematical models are developed to predict the local concentration and spatial distribution of free and bound VEGF165 within the gel matrices. The results of simulation and experimental studies concordantly reveal how the GAG concentration and sulfation pattern determine the local availability of VEGF165 within the cell‐instructive hydrogels and how the factor—in interplay with cell‐instructive gel properties—determines the formation and spatial organization of capillary networks of embedded human vascular endothelial cells. Taken together, this study exemplifies how mathematical modeling and rational hydrogel design can be combined to pave the way for precision tissue engineering.