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

Supramolecular Self-Assemblies with Nanoscale RGD Clusters Promote Cell Growth and Intracellular Drug Delivery

In this work, we reported the generation of a novel supramolecular hydrogelator from a peptide derivative which consisted of a structural motif (e.g., Fc-FF) for supramolecular self-assembly and a functional moiety (e.g., RGD) for integrin binding. Following self-assembly in water at neutral pH, this molecule first tended to form metastable spherical aggregates, which subsequently underwent a morphological transformation to form high-aspect-ratio nanostructures over 2 h when aged at room temperature. More importantly, because of the presence of nanoscale RGD clusters on the surface of nanostructures, the self-assembled nanomaterials (e.g., nanoparticles and nanofibers) can be potentially used as a biomimetic matrix for cell culture and as a vector for cell-targeting drug delivery via multivalent RGD–integrin interactions

Peptide Glycosylation Generates Supramolecular Assemblies from Glycopeptides as Biomimetic Scaffolds for Cell Adhesion and Proliferation

Glycopeptide-based hydrogelators with well-defined molecular structures and varied contents of sugar moieties were prepared via in vitro peptide glycosylation reactions. With systematic glucose modification, these glycopeptide hydrogelators exhibited diverse self-assembling behaviors in water and formed supramolecular hydrogels with enhanced thermostability and biostability, in comparison with their peptide analogue. Moreover, because of high water content and similar structural morphology and composition to extracellular matrixes (ECM) in tissues, these self-assembled hydrogels also exhibited great potential to act as new biomimetic scaffolds for mammalian cell growth. Therefore, peptide glycosylation proved to be an effective means for peptide modification and generation of novel supramolecular hydrogelators/hydrogels with improved biophysical properties (e.g., high biostability, increased thermostability, and cell adhesion) which could promise potential applications in regenerative medicine