Viscoelastic Hydrogels for Stem Cell Behavior and Tissue Engineering

Viscoelastic hydrogels combine the fluid-like viscous response and the solid-like elastic response of natural extracellular matrices to present time-dependent mechanical cues to embedded cells. Unlike purely elastic substrates, these materials dissipate stress over physiologically relevant timescales, enabling cells to remodel their surroundings and to engage in dynamic mechano-chemical feedback. By tuning parameters such as stress-relaxation rate, storage and loss moduli, and reversible crosslink kinetics, researchers can direct stem cell spreading, proliferation and lineage commitment within three-dimensional environments. Such control over mechanotransduction pathways has led to advances in organoid formation, bone and cartilage repair strategies, and the design of implantable scaffolds that better mimic native tissue mechanics. The global significance of this field lies in its potential to enhance regenerative outcomes, reduce reliance on donor tissues and accelerate the translation of stem cell therapies into clinical practice.

Research from Nature Portfolio

Recent studies have revealed that hydrogels engineered with rapid stress-relaxation kinetics promote volume expansion in mesenchymal stem cells, triggering the activation of TRPV4 ion channels and subsequent nuclear localisation of osteogenic transcription factors. In parallel, investigations into dynamic crosslink networks have shown that fast-dissociating bonds permit cell-induced network reorganisation, resulting in ultra-rapid stellate spreading, enhanced force generation and accelerated differentiation of encapsulated stem cells. Together, these works highlight the central role of relaxation rate and bond exchange dynamics in guiding stem cell fate decisions within viscoelastic matrices.

Research from all publishers

Colloidal hydrogels assembled from gelatin nanoparticles exhibit strain-dependent fluidisation at levels matching cell-applied deformations, delivering fast exponential stress relaxation and enabling efficient stem cell migration and matrix remodelling. Modifying interparticle attractions in these systems tunes relaxation rates and influences cell-mediated matrix organisation. Meanwhile, soft, stress-relaxing hydrogels designed for kidney organoid culture improve lumen morphology, reduce epithelial-mesenchymal transition markers and support the emergence of multiple renal segments. Such materials demonstrate how bespoke viscoelastic profiles can foster organ-specific tissue architecture and enhance the functional maturation of stem cell-derived constructs.

Viscoelastic Hydrogels for Stem Cell Behavior and Tissue Engineering publication trend

The graph below shows the total number of articles in viscoelastic hydrogels for stem cell behavior and tissue engineering across all publications each year (not limited to Nature Index journals).

Technical terms

Viscoelasticity: The property of a material to exhibit both time-dependent flow (viscous) and reversible deformation (elastic) responses under stress.

Stress relaxation: The decline in internal stress over time when a material is held at a fixed deformation, reflecting its capacity to dissipate mechanical energy.

Storage modulus: A measure of the elastic component of a material under oscillatory loading, indicating its ability to store energy elastically.

Loss modulus: A measure of the viscous component of a material under oscillatory loading, indicating its capacity to dissipate energy as heat.

Mechanotransduction: The process by which cells sense mechanical characteristics of their environment and convert them into biochemical signals.

Dynamic crosslink: A reversible bonding interaction within a polymer network that can break and reform, permitting adaptive remodelling of the hydrogel structure.

References

1. Volume expansion and TRPV4 activation regulate stem cell fate in three-dimensional microenvironments. Nature Communications (2019).
2. Enhanced mechanosensing of cells in synthetic 3D matrix with controlled biophysical dynamics. Nature Communications (2021).
3. Colloidal hydrogels made of gelatin nanoparticles exhibit fast stress relaxation at strains relevant for cell activity. Acta Biomaterialia (2021).
4. Soft, Dynamic Hydrogel Confinement Improves Kidney Organoid Lumen Morphology and Reduces Epithelial–Mesenchymal Transition in Culture. Advanced Science (2022).