<p>A major challenge in tissue engineering involves the development of synthetic biomaterials that effectively induce and maintain functional vascularization of engineered tissue constructs post implantation. While conjugating heparin to a dextran hydrogel developed a pro-angiogenic scaffold that led to substantial endothelial multicellular assembly in vitro and enhanced host vessel invasion in vivo, the inherent anti-coagulant bioactivities of native heparin elicited substantial local bleeding upon implantation. To decouple the pro-angiogenic effects from the anti-coagulant activity, we developed a synthetic, heparin-mimetic material by introducing sulfate adducts to the dextran backbone. These heparin-mimetic hydrogels bound and immobilized growth factors, enhanced angiogenic signaling, and promoted both in vitro vascular network formation in 3D and in vivo tissue microvascularization to a similar extent as heparin conjugated hydrogels, but without inducing local bleeding at implantation sites. This development of a fully synthetic, highly tunable angiogenic biomaterial provides a new material system to engineer functional vascularized tissues.</p>