Northeastern University Background
Biomaterial‑based scaffolds are being used as 3D culture systems in vitro and as molecular and cellular delivery vehicles in vivo. To support cellular survival, activation, and differentiation, cells need to be provided with biomolecular cues that trigger specific signaling pathways. To facilitate survival and expansion of primary T lymphocytes, biomolecules that trigger T-cell receptor signaling and provide co-stimulatory cues are required. Therefore, biomolecules such as activating antibodies, protein complexes and polysaccharides need to be integrated into biomaterial-based scaffolds. These can be incorporated in various ways (e.g. through physical entrapment or ionic interaction), but these strategies do not result in the stable or controlled presentation of biomolecules. Instead, covalent attachment is favored to ensure the sustained availability of these signals in a controlled manner.
This invention focuses on covalent attachment of a wide range of biomolecules onto pre-formed 3D biomaterial-based cryogels. These macroporous cryogels based on hyaluronic acid (HA) or alginate are formed by cryogenic polymerization of methacrylated HA or alginate polymers. The resulting scaffolds are biocompatible, non-immunogenic, support cell survival and display favorable mechanical properties.
Northeastern researchers have developed a versatile and straightforward strategy to covalently couple activating antibodies, protein complexes and polysaccharides to these pre-formed cryogels. This established presence of co-monomers during cryogelation is required to enable and facilitate attachment of biomolecules to the cryogel post-fabrication. This system provides a highly modular platform to functionalize 3D cryogel scaffolds, and owing to their syringe injectability, these cryogels can easily be applied in vivo.
Efficient and easy to work
Easy to wash away potential toxic molecules used for labeling
Bioavailability of molecules is retained as molecules are not exposed to freeze/thawing and free-radical polymerization during cryogel formation
3D culture system to provide cells with stimulatory/survival cues
A tool to study ex vivo interaction of cells and molecular cues in a controlled context
Enhance immunotherapeutic approaches