Surface Roughness and Substrate Stiffness Synergize To Drive Cellular Mechanoresponse

Area of Science:

• Biomaterials Science
• Cell Biology
• Tissue Engineering

Background:

• Material surface topography is critical for tissue regeneration and medical implants.
• Previous studies on cell response to surface roughness yielded conflicting results due to complex interplay with substrate stiffness.

Purpose of the Study:

• To investigate the mechanosensitive response of human mesenchymal stem cells (MSCs) to a wide range of surface roughness and substrate stiffnesses.
• To elucidate the combined effects of topography and mechanics on stem cell behavior.

Main Methods:

• Fabrication of hydrogels with a wide range of surface roughness (nanoscale to microscale) and controllable stiffness using soft lithography.
• Systematic study of MSCs' response to varying roughness and stiffness, including cellular mechanoresponse and osteogenesis.

Main Results:

• MSCs exhibited stiffness-dependent responses to surface roughness, altering their surface hierarchical structure.
• Significantly enhanced MSC mechanoresponse and osteogenesis were observed on soft hydrogels (3.8 kPa) with high surface roughness.
• Performance on soft, rough surfaces was comparable or superior to smooth, stiff substrates.

Conclusions:

• Cellular response to biomaterial surface topography is strongly influenced by substrate stiffness.
• Synergistic physical cues from combined surface roughness and stiffness can effectively regulate stem cell fate and enhance osteogenesis.
• This work provides a novel approach for noninvasively controlling stem cell behavior for regenerative medicine applications.