Unravelling the synergies: effects of hydrogel mechanics and biofunctionalization on mesenchymal stem cell osteogenic differentiation

Abstract

The design of hydrogels for cell culture that mimic the extracellular matrix is complex given the numerous factors involved. This study explores the synergistic effects of mechanical properties and biofunctionalization on mesenchymal stem cell (MSC) differentiation, with a focus on bone regeneration. Although the influence of the elastic and viscoelastic properties of hydrogel matrices on stem cell differentiation is well recognized, the impact of viscoelasticity is still poorly understood. In addition, the synergistic interaction between viscoelastic properties and biofunctionalization remains poorly understood. In this work, poly(ethylene glycol)diacrylate (PEGDA) hydrogels were designed with varying shear moduli and loss tangents. This research uniquely investigates the combined effects of mechanical properties and biofunctionalization, by co-functionalizing the hydrogels with a mixture of RGD and a BMP-2 mimetic peptide. This dual approach allowed for an in-depth analysis of the synergies between mechanics and bioactivity, as well as the impact of different peptide combinations. Our results demonstrated that the mechanical properties of hydrogels are a primary factor in driving differentiation, as biofunctionalization alone is not sufficient to induce this process. Additionally, our study underscores the significant impact of the lesser-known viscoelastic properties on MSC differentiation into an osteoblastic lineage, even after just one week of culture.