Bioactive Nonthermal Biocompatible Plasma Enhances Migration on Human Gingival Fibroblasts

• Published in: Advanced healthcare materials 2023-02, Vol.12 (4), p.e2200527-n/a
• Main Authors: Han, Ihn, Song, In‐Seok, Choi, Seung Ah, Lee, Taebok, Yusupov, Maksudbek, Shaw, Priyanka, Bogaerts, Annemie, Choi, Eun Ha, Ryu, Jae Jun
• Format: Article
• Language: English
• Subjects: Actin; Amino acids; Attenuation; Biocompatibility; catalytic kinase domain; Cell cycle; Cell death; Cell migration; Cell Movement; Cells, Cultured; Cyclin-dependent kinase inhibitor p21; Cytoskeleton; Dielectric barrier discharge; Extracellular matrix; Fibroblasts; Focal adhesion kinase; focal adhesion kinase signaling; Focal Adhesion Protein-Tyrosine Kinases - metabolism; Gingiva; Humans; Kinases; Mathematical models; Matrix metalloproteinase; Matrix metalloproteinases; Metalloproteinase; migration; nonthermal biocompatible plasma; oral wound healing; Oxidation; Plasma; Protein structure; Wound Healing
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202200527

This study hypothesizes that the application of low‐dose nonthermal biocompatible dielectric barrier discharge plasma (DBD‐NBP) to human gingival fibroblasts (HGFs) will inhibit colony formation but not cell death and induce matrix metalloproteinase (MMP) expression, extracellular matrix (ECM) degradation, and subsequent cell migration, which can result in enhanced wound healing. HGFs treated with plasma for 3 min migrate to each other across the gap faster than those in the control and 5‐min treatment groups on days 1 and 3. The plasma‐treated HGFs show significantly high expression levels of the cell cycle arrest‐related p21 gene and enhanced MMP activity. Focal adhesion kinase (FAK) mediated attenuation of wound healing or actin cytoskeleton rearrangement, and plasma‐mediated reversal of this attenuation support the migratory effect of DBD‐NBP. Further, this work performs computer simulations to investigate the effect of oxidation on the stability and conformation of the catalytic kinase domain (KD) of FAK. It is found that the oxidation of highly reactive amino acids (AAs) Cys427, Met442, Cys559, Met571, Met617, and Met643 changes the conformation and increases the structural flexibility of the FAK protein and thus modulates its function and activity. Low‐dose DBD‐NBP‐induces host cell cycle arrest, ECM breakdown, and subsequent migration, thus contributing to the enhanced wound healing process. Nonthermal biocompatible plasma (NBP) stimulates human gingival fibroblast (HGF) cell migration through focal adhesion kinase (FAK) pathway. NBP would inhibit colony formation and induce matrix metalloproteinase (MMP) expression, extracellular matrix (ECM) degradation, and subsequent cell migration. NBP plays a role in cell motility to regulate AKT and p21 signals in HGF cells, through actin modification of cytoskeleton.