Measuring human mesenchymal stem cell remodeling in hydrogels with a step-change in elastic modulus

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Cell Biology

Background:

• Human mesenchymal stem cells (hMSCs) are crucial for wound healing, migrating to injury sites to reduce inflammation and promote regeneration.
• Implantable hydrogels delivering hMSCs offer potential for improved wound healing, especially in chronic wounds.
• Effective cell delivery requires hMSC migration from the scaffold into surrounding tissue, necessitating migration across material property interfaces.

Purpose of the Study:

• To investigate human mesenchymal stem cell (hMSC) migration and remodeling within a 3D hydrogel exhibiting a distinct stiffness gradient.
• To characterize the pericellular environment's structural and rheological changes during hMSC migration across an interface.
• To provide data for designing improved cell-laden hydrogel scaffolds for enhanced wound healing.

Main Methods:

• Fabrication of a cell-degradable hydrogel (poly(ethylene glycol)-norbornene) with two distinct stiffnesses separated by a rapid interface.
• Encapsulation of hMSCs within the hydrogel and assessment of 3D migration and remodeling.
• Utilizing multiple particle tracking microrheology (MPT) to analyze pericellular region structure and rheology over time.

Main Results:

• hMSCs exhibited greater remodeling in the softer hydrogel region compared to the stiffer region at day 1 post-encapsulation.
• Remodeling became more uniform across all regions by day 6.
• Significant hMSC-mediated remodeling occurred along the interface, with cells migrating towards the stiffer hydrogel side.

Conclusions:

• hMSC migration and remodeling are influenced by hydrogel stiffness gradients.
• The interface region shows active cell-mediated remodeling and directed migration.
• Findings can inform the design of advanced biomaterials for enhanced cell delivery and wound regeneration.