Tuning the Local Availability of VEGF within Glycosaminoglycan‐Based Hydrogels to Modulate Vascular Endothelial Cell Morphogenesis. (10th May 2020)

• Record Type: Journal Article
• Authors: Limasale, Yanuar Dwi Putra; Atallah, Passant; Werner, Carsten; Freudenberg, Uwe; Zimmermann, Ralf
• Is Part Of: Advanced functional materials. Volume 30:Number 44(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-05-10
• Subjects: angiogenesis -- diffusion -- glycosaminoglycans -- hydrogels -- VEGF; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.202000068
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: 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. Abstract : Biomolecular interaction analysis and computational modeling are used to tailor the glycosaminoglycan concentration and sulfation pattern of star‐shaped poly(ethylene glycol)–glycosaminoglycan hydrogels for modulating the local availability of the vascular endothelial growth factor (VEGF165) and, by that, the tubular morphogenesis of gel‐embedded human vascular endothelial cells.