Precision design of dextran-permeated agarose hydrogels matching adipose stem cell adhesion timescales.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Viscoelasticity is now recognised as a key parameter in modulating cell behaviour. Tailoring time-dependent materials to elicit specific cellular responses is, however, a challenge because of the intricate relationship between the substrate relaxation time (τ rel ) and the cell sensing time-window which depends on the time required for the formation of focal adhesions (τ b ) and the duration of their lifetime (τ L ). Here, we introduce a novel design approach to guide cell behaviour based on the cell-perceived Deborah number, De = τ rel /τ L, arguing that for De > 1 and De < 1, substrates promote cell differentiation because stable adhesions and sustained tension drive mechanotransduction and lineage-specific differentiation on the basis of substrate stiffness. Instead, cell stemness is maintained in the De ∼1, whereby excessive mechanical signalling is prevented as cells balance adhesion stability and plasticity. The design workflow consists in modelling substrate τ rel , enabling the selection of the optimal gel formulation according to the cell-perceived De. The workflow was applied to agarose gels with different dextran concentrations in the liquid phase, which act as modulators of mechanical time-dependent properties. To predict the relaxation times for these gels, we developed an in-silico model which integrates their structural and transport properties. Our results show

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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