Year: 2025
Type: article
Abstract: 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. Synthetic heparin-mimetic hydrogels immobilize angiogenic growth factors to promote tissue vascularization, providing salient properties of heparin-containing materials in promoting angiogenesis without the associated risk of bleeding.
Source: Communications Biology
Institutions: Boston University, Harvard University, University of New Hampshire, Wyss Institute for Biologically Inspired Engineering, Broad Institute, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard–MIT Division of Health Sciences and Technology, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Awards: G1199548893, G1268470567, G3040271031, G3077360251, RII-Track 1: New Hampshire Center for Multiscale Modeling and Manufacturing of Biomaterials (NH Bio-Made), G4481177325, G7972811684, Combining soluble and bound factors in microstructured hydrogels to promote chronic wound angiogenesis and healing, Science and Technology Center for Engineering Mechano-Biology
OpenAlex ID: W4416225757