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

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Cellular Mechanobiology

Background:

• Tissues possess unique mechanical properties like stiffness and viscoelasticity, influencing cellular behavior.
• Dynamic hydrogels, engineered via physical interactions or dynamic covalent bonds (DCBs), leverage these cues.
• Viscoelastic hydrogels show promise for directing mesenchymal stem cell (MSC) behavior in bone tissue engineering (BTE).

Purpose of the Study:

• Systematically review dynamic hydrogel crosslinking strategies.
• Summarize methods for quantitative viscoelastic modulation.
• Elucidate mechanotransduction pathways governing MSCs for BTE.

Main Methods:

• Review of dynamic hydrogel crosslinking chemistries (ionic, H-bonding, DCBs like hydrazone, boronate ester, imine).
• Analysis of viscoelastic modulation via molecular weight, crosslinking chemistry, and network architecture.
• Examination of mechanotransduction pathways (integrin-FAK, TRPV4, Piezo1) and YAP/TAZ signaling.

Main Results:

• Viscoelastic effects are context-dependent, influenced by cell source, dimensionality, and matrix chemistry.
• YAP/TAZ acts as a central node integrating various mechanosensory inputs.
• Clinical translation faces challenges in standardization, in vivo validation, and manufacturing.

Conclusions:

• Rational design of ECM-mimetic dynamic hydrogels is crucial for bone and cartilage regeneration.
• Understanding mechanotransduction pathways is key to controlling MSC fate.
• Addressing translational challenges is necessary for clinical application of dynamic hydrogels.