Protease-Sensitive Hydrogel Biomaterials with Tunable Modulus and Adhesion Ligand Gradients for 3D Vascular Sprouting
journal contributionposted on 2018-09-25, 00:00 authored by Yusheng J. He, Daniel A. Young, Merjem Mededovic, Kevin Li, Chengyue Li, Kenneth Tichauer, David Venerus, Georgia Papavasiliou
Biomaterial strategies focused on designing scaffolds with physiologically relevant gradients provide a promising means for elucidating 3D vascular cell responses to spatial and temporal variations in matrix properties. In this study, we present a photopolymerization approach, ascending photofrontal free-radical polymerization, to generate proteolytically degradable hydrogel scaffolds of poly(ethylene) glycol with tunable continuous gradients of (1) elastic modulus (slope of 80 Pa/mm) and uniform immobilized RGD concentration (2.06 ± 0.12 mM) and (2) immobilized concentration of the RGD cell-adhesion peptide ligand (slope of 58.8 μM/mm) and uniform elastic modulus (597 ± 22 Pa). Using a coculture model of vascular sprouting, scaffolds embedded with gradients of elastic modulus induced increases in the number of vascular sprouts in the opposing gradient direction, whereas RGD gradient scaffolds promoted increases in the length of vascular sprouts toward the gradient. Furthermore, increases in vascular sprout length were found to be prominent in regions containing higher immobilized RGD concentration.
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3 D Vascular Sprouting Biomaterial strategiescell responsesProtease-Sensitive Hydrogel Biomaterialsproteolytically degradable hydrogel scaffoldsmoduluTunable Modulusphotofrontal free-radical polymerizationRGD gradient scaffoldselucidating 3 DRGD concentrationgradient directionmatrix propertiescoculture modelAdhesion Ligand GradientsRGD cell-adhesion peptide ligandphotopolymerization approach