Silk Hydrogel Substrate Stress Relaxation Primes Mesenchymal Stem Cell Behavior in 2D

Area of Science:

• Biomaterials Science
• Stem Cell Biology
• Tissue Engineering

Background:

• Silk hydrogels are promising for healthcare applications like stem cell delivery.
• The mechanical properties of silk hydrogels, specifically stress relaxation, are not well understood in relation to human mesenchymal stem cell (MSC) biology.

Purpose of the Study:

• To fabricate silk hydrogels with tunable mechanical properties.
• To investigate how these mechanical properties regulate MSC biology in 2D culture.
• To compare the effects of elastic versus viscoelastic silk hydrogels on MSCs.

Main Methods:

• Fabrication of elastic and viscoelastic silk hydrogels with constant silk content and stiffness.
• Culturing human MSCs on these hydrogels.
• Analysis of gene and protein expression.
• Metabolic profiling of MSCs.

Main Results:

• Elastic hydrogels upregulated inflammatory genes (IL-1β, IL-6) and downregulated stem cell markers (SOX-2) compared to viscoelastic hydrogels.
• MSC protein expression and IL-1β signaling were mechanosensitive.
• Elastic substrates increased glucose and aspartate consumption and lactate secretion, indicating altered MSC metabolism.

Conclusions:

• Stress relaxation in silk hydrogels significantly impacts MSC gene expression, protein signaling, and metabolic activity.
• Tailoring silk hydrogel mechanics can modulate MSC behavior for potential therapeutic applications.