Effect of mechanical loading and substrate elasticity on the osteogenic and adipogenic differentiation of mesenchymal stem cells
Hatice Imran Gungordu
Department of Biomaterials, Radboud University Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorMin Bao
Department of Physical Organic Chemistry, Radboud University, Nijmegen, The Netherlands
Search for more papers by this authorSjoerd van Helvert
Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorJohn A. Jansen
Department of Biomaterials, Radboud University Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorSander C.G. Leeuwenburgh
Department of Biomaterials, Radboud University Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorCorresponding Author
X. Frank Walboomers
Department of Biomaterials, Radboud University Medical Center, Nijmegen, The Netherlands
Correspondence
X. Frank Walboomers, PhD, Dentistry, Department of Biomaterials, Radboud University Medical Center, P.O. Box 9101 6500 HB Nijmegen, The Netherlands.
Email: [email protected]
Search for more papers by this authorHatice Imran Gungordu
Department of Biomaterials, Radboud University Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorMin Bao
Department of Physical Organic Chemistry, Radboud University, Nijmegen, The Netherlands
Search for more papers by this authorSjoerd van Helvert
Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorJohn A. Jansen
Department of Biomaterials, Radboud University Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorSander C.G. Leeuwenburgh
Department of Biomaterials, Radboud University Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorCorresponding Author
X. Frank Walboomers
Department of Biomaterials, Radboud University Medical Center, Nijmegen, The Netherlands
Correspondence
X. Frank Walboomers, PhD, Dentistry, Department of Biomaterials, Radboud University Medical Center, P.O. Box 9101 6500 HB Nijmegen, The Netherlands.
Email: [email protected]
Search for more papers by this authorAbstract
Mesenchymal stem cells (MSCs) are highly sensitive to biomechanics of their extracellular environment. Generally, a higher elasticity of culture substrates can drive cells into the osteogenic lineage, whereas low substrate elasticity results in adipogenesis. Applied mechanical loading by cyclic strain is another major variable influencing cell fate. Yet, little is known about the simultaneous effect of both cues. Therefore, the present study investigated the relative importance of both cues on differentiation. MSCs were cultured in an osteogenic and also an adipogenic environment on soft polyacrylamide (PAAm; E = 23 ± 0.3 kPa), stiff PAAm (111 ± 2 kPa), and polydimethylsiloxane (PDMS; E = 1,5 ± 0.07 MPa) either unstrained or with 8% cyclic strain at 1 Hz. Without strain, the relative expression of the early osteogenic marker alkaline phosphatase (ALP) was significantly higher (78%) on PDMS than on both PAAm. With 8% cyclic strain, ALP expression increased for all groups in comparison with unstrained controls. The highest increase was observed for the soft PAAm by 36%. Moreover, relative oil red O (ORO) expression—indicating adipogenesis—was the highest for unstrained soft PAAm. On the other hand, the percentage of ORO positive cells significantly decreased by 57% and 69% for soft and stiff PAAm when strained. In conclusion, biomaterial elasticity and mechanical loading can act simultaneously on cell differentiation. Substrate elasticity is an important factor, regulating the differentiation, but cyclic strain can drive MSCs towards the osteogenesis even on the softest substrate. As such, the osteogenic effect of mechanical loading can overrule the adipogenic effect of soft substrates, thereby acting as an inhibitor.
CONFLICT OF INTEREST
The authors claim no conflicts of interest related to this manuscript.
Supporting Information
| Filename | Description |
|---|---|
| term2956-sup-0001_F1.mp4MPEG-4 video, 8 MB |
Video S1. Video of Mechanical loading application |
| term2956-sup-0002_F2.jpgJPEG image, 12.7 KB |
Figure S2. Mechanical strain transfer images |
| term2956-sup-0003_F3.jpgJPEG image, 29.5 KB |
Figure S3. Cell viability on PDMS and PAAm 7 days after seeding |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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