Enzymatic Formation of an Injectable Hydrogel from a Glycopeptide as a Biomimetic Scaffold for Vascularization

The construction of functional vascular networks in regenerative tissues is a crucial technology in tissue engineering to ensure the sufficient supply of nutrients. Although natural hydrogels are highly prevalent in fabricating three-dimensional scaffolds to induce neovascular growth, their widespread applicability was limited by the potential risk of immunogenicity or pathogen transmission. Therefore, developing hydrogels with good biocompatibility and cell affinity is highly desirable for fabricating alternative matrices for tissue regeneration applications. Herein, we report the generation of a new kind of hydrogel from supramolecular assembling of a synthetic glycopeptide to mimic the glycosylated microenvironment of extracellular matrix. In the presence of a tyrosine phosphate group, this molecule can undergo supramolecular self-assembling and gelation triggered by alkaline phosphatase under physiological conditions. Following supramolecular self-assembling, the glycopeptide gelator tended to form nanofilament structures displaying a high density of glucose moieties on their surface for endothelial cell adhesion and proliferation. On further incorporation with deferoxamine (DFO), the self-assembled hydrogel can serve as a reservoir for sustainably releasing DFO and inducing endothelial cell capillary morphogenesis in vitro. After subcutaneous injection in mice, the glycopeptide hydrogel encapsulating DFO can work as an effective matrix to trigger the generation of new blood capillaries in vivo.