A collagen mimetic peptide-modified hyaluronic acid hydrogel system with enzymatically mediated degradation for mesenchymal stem cell differentiation.

We have successfully designed and synthesized a biomimetic hydrogel system with maleimide-modified hyaluronic acid (HA) as the backbone and conjugated it to the collagen mimetic peptide (GPO)-CG-RGDS. The matrix metalloproteinase (MMP)-sensitive peptide GCRDGPQGI↓WGQDRCG was the cross-linker. HA has high biocompatibility, low immunogenicity, and the capacity to interact with extracellular molecules. Recent studies have found that matrix metalloproteinases (MMPs) are involved in regulating the differentiation of bone mesenchymal stem cells and play a pivotal role in cartilage formation. (GPO)-CG-RGDS has a natural collagen partial structure that follows the (Gly-Xaa-Yaa)n sequence, which is controllable in quality and can mimic the structure and biological activity of natural collagen. We found that combining this CMP with a MMP-sensitive peptide may have the potential to induce the differentiation of BMSCs into cartilage and inhibit the hypertrophic phenotype during differentiation. This design allows HA hydrogels to not only bind RGD sequences but also graft other functional peptide sequences to achieve a highly flexible platform with potential for multiple biomedical applications.