한빛사논문
Rajendra K. Singh1,2*, Amal George Kurian1,2, Varsha Sagar1,2, Ilyong Park3, Jeong-Hui Park1,2,3,4, Hwalim Lee1,3, Jung-Hwan Lee1,2,4,5,6,7,8*, Hae-Won Kim1,2,4,5,6,7,8*
1Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116 Republic of Korea
2Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, 31116 Cheonan, Republic of Korea
3Department of Biomedical Engineering, College of Medicine, Dankook University, Cheonan, 31116 Republic of Korea
4UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116 Republic of Korea
5Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116 Republic of Korea
6Department of Regenerative Dental Medicine, College of Dentistry, Dankook University, Cheonan, 31116 Republic of Korea
7Cell & Matter Institute, Dankook University, Cheonan, 31116 Republic of Korea
8Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116 Republic of Korea
*CORRESPONDING AUTHORS : Rajendra K. Singh, Jung-Hwan Lee, Hae-Won Kim
Abstract
Biophysical stimulation regulates stem cell functions, including proliferation and differentiation. Matrix nanotopography and external forces, such as electromagnetic fields (EMF), can enhance this stimulation. Here, it is demonstrated that biophysical multiple cues coordinated from electromagnetized Au-nanoparticles-decorated polymer nanofiber under EMF significantly regulate the adhesion, alignment, proliferation, and lineage commitment of hMSCs. Without EMF, matrix cues of electrical conductivity and nanodotted fibrous topography accelerate the anchorage and spreading of hMSCs. Of note, EMF synergizes with the matrix cues to enhance cellular behaviors, resulting in elongated and aligned cells along the field direction. Microtubules are highly polymerized, acetylated, and aligned, playing an active role in these events. Actin filaments also develop in parallel with the microtubules, facilitating actin-microtubule crosstalks. These phenomena lead to changes in the nuclear mechanics of hMSCs, including elongated nuclear shape and decondensed chromatins with histone acetylation. The EMF+matrix-stimulated hMSCs express genes related to microtubule organization and euchromatin, as revealed by RNA sequencing, and show chromatin accessibility with enrichment of genes related to mechanotransduction and lineage specification, as analyzed by ATAC sequencing. The EMF+matrix biophysical stimulation further increases the capacity for lineage specification (predominantly towards osteogenic, myogenic, and tenogenic), offering a promising bioengineering platform for stem cell engineering and therapies.
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