Glycosaminoglycan (GAG) Biomaterials for Protein Delivery and Cell Differentiation
The Temenoff laboratory has demonstrated the power of modification of a key component of the extracellular matrix (GAGs) to affect protection and release of growth factors as well as influence mesenchymal stem cell (MSC) differentiation. To accomplish this, our lab has developed multiple families of GAGs with controlled sulfation patterns and further modified them to be crosslinkable for inclusion in hydrogel and microparticle biomaterials.
To investigate interactions between GAGs and therapeutic growth factors, we have explored the ability of several heparin species with controlled desulfation to protect the growth factor Bone Morphogenetic Protein-2 (BMP-2) from denaturation. Overall results suggest that desulfation may be needed at only one position to maintain the ability for the GAG to complex and protect the growth factor within a biomaterial carrier, while simultaneously reducing the anti-coagulatory effects of heparin (which are also sulfation-pattern dependent) to make future heparin-based biomaterials safe for in vivo growth factor delivery applications.
In terms of interactions with cells, we have shown that level of sulfation in crosslinked GAG-based hydrogels can affect mesenchymal stem cell differentiation towards chondrocytes in the presence of the chondrogenic growth factor TGF-β1. To further increase the amount of GAG available to interact with cells, a novel means of coating the surface of cells with GAGs has also been developed in our laboratory.