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Porous Scaffold-Hydrogel Composites Spatially Regulate 3D Cellular Mechanosensing
Matthew DiCerbo1, Mohammed Mehdi Benmassaoud1, Sebastián L Vega1
1Department of Biomedical Engineering, Rowan University, Glassboro, NJ, United States.
Frontiers in Medical Technology
|May 19, 2022
Summary
Hydrogel stiffness influences human mesenchymal stem cell (MSC) behavior and mechanosensing. This study shows how varying mechanical stress in 3D biomaterials affects cell volume and YAP localization, aiding tissue interface design.
Area of Science:
- Biomaterials Science
- Cellular Mechanobiology
- Tissue Engineering
Background:
- Cells in 3D hydrogels show varied mechanosensing based on their ability to remodel the matrix.
- Recreating the diverse mechanosensitive states found in tissue interfaces within 3D biomaterials is challenging.
- Human mesenchymal stem cells (MSCs) remodel methacrylated gelatin (GelMe) hydrogels over time, increasing cell volume and nuclear YAP localization.
Purpose of the Study:
- To investigate the role of spatial differences in hydrogel stress on 3D cellular mechanosensing.
- To evaluate how mechanical stress affects MSC morphology and YAP localization in engineered biomaterials.
- To develop novel biomaterials for studying and designing tissue interfaces with heterogeneous mechanical signals.
Main Methods:
- Finite element analysis modeled stress distribution in compressed GelMe hydrogels.
- MSC-laden GelMe hydrogels were compressed (0-50%) to assess mechanosensing under varying stress.
- Porous polycaprolactone (PCL) scaffolds were perfused with MSC-laden GelMe to create composite materials with heterogeneous mechanical environments.
Main Results:
- MSCs at the edge (high stress) of 25% compressed hydrogels were larger, less round, and had increased nuclear YAP compared to those in the center (low stress).
- 50% compression led to uniform high stress and increased MSC volume and nuclear YAP throughout the hydrogel.
- MSCs within PCL-hydrogel composites exhibited a wider range of morphology and nuclear YAP with increasing pore size, indicating sensitivity to diverse mechanical signals.
Conclusions:
- Hydrogel stress significantly influences MSC mechanosensing, affecting cell volume and YAP localization.
- Porous scaffold-hydrogel composites offer a promising platform for mimicking the heterogeneous mechanical cues of tissue interfaces.
- These biomaterials can be utilized for studying cell-material interactions and designing advanced tissue engineering constructs.

