Dynamic hydrogels for bone tissue engineering: modulating the fate of resident MSCs

Abstract

Different tissues exhibit distinct mechanical properties, including stiffness and viscoelasticity. Both static and dynamic mechanical cues modulate cellular behaviour and induce phenotypic changes. To leverage this regulatory mechanism, researchers have engineered dynamic hydrogels through physical interactions and dynamic covalent bonds (DCBs). Prior studies demonstrate that viscoelastic hydrogels effectively direct mesenchymal stem cell (MSC) behaviour, making them promising candidates for bone tissue engineering (BTE). This review systematically summarizes (i) dynamic hydrogel crosslinking strategies (ionic, hydrogen bonding, hydrazone, boronate ester, and imine), (ii) quantitative viscoelastic modulation methods (molecular weight, crosslinking chemistry, and network architecture), and (iii) mechanotransduction pathways governing MSC proliferation, spreading, migration, osteogenesis, and chondrogenesis. Several conclusions emerge from the above perspectives: viscoelastic effects are context-dependent, varying with the cell source, dimensionality, and matrix chemistry; YAP/TAZ serves as a convergent node integrating diverse mechanosensory inputs (integrin–FAK, TRPV4, and Piezo1) into lineage-specific programs; and clinical translation faces persistent challenges from non-standardized characterization protocols, limited long-term in vivo validation, and scalable manufacturing constraints. By integrating these perspectives, this review aims to develop the rational design of ECM-mimetic dynamic hydrogels for bone and cartilage regeneration.