Fracture healing on non-union fracture model promoted by non-thermal atmospheric-pressure plasma

Kosuke Saito; Hiromitsu Toyoda; Mitsuhiro Okada; Jun-Seok Oh; Katsumasa Nakazawa; Yoshitaka Ban; Kumi Orita; Akiyoshi Shimatani; Hana Yao; Tatsuru Shirafuji; Hiroaki Nakamura

doi:10.1371/journal.pone.0298086

Fracture healing on non-union fracture model promoted by non-thermal atmospheric-pressure plasma

PLoS One. 2024 Apr 16;19(4):e0298086. doi: 10.1371/journal.pone.0298086. eCollection 2024.

Authors

Kosuke Saito¹, Hiromitsu Toyoda^{1

2}, Mitsuhiro Okada^{1

2}, Jun-Seok Oh³, Katsumasa Nakazawa¹, Yoshitaka Ban¹, Kumi Orita², Akiyoshi Shimatani⁴, Hana Yao², Tatsuru Shirafuji³, Hiroaki Nakamura^{1

2}

Affiliations

¹ Department of Orthopedic Surgery, Graduate School of Medicine, Osaka City University, Osaka, Japan.
² Department of Orthopedic Surgery, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
³ Department of Physics and Electronics, Graduate School of Engineering, Osaka Metropolitan University, Osaka, Japan.
⁴ Department of Orthopedic Surgery, Saiseikai Nakatsu Hospital, Osaka, Japan.

Abstract

Non-thermal atmospheric-pressure plasma (NTAPP) is attracting widespread interest for use in medical applications. The tissue repair capacity of NTAPP has been reported in various fields; however, little is known about its effect on fracture healing. Non-union or delayed union after a fracture is a clinical challenge. In this study, we aimed to investigate how NTAPP irradiation promotes fracture healing in a non-union fracture model and its underlying mechanism, in vitro and in vivo. For the in vivo study, we created normal and non-union fracture models in LEW/SsNSlc rats to investigate the effects of NTAPP. To create a fracture, a transverse osteotomy was performed in the middle of the femoral shaft. To induce the non-union fracture model, the periosteum surrounding the fracture site was cauterized after a normal fracture model was created. The normal fracture model showed no significant difference in bone healing between the control and NTAPP-treated groups. The non-union fracture model demonstrated that the NTAPP-treated group showed consistent improvement in fracture healing. Histological and biomechanical assessments confirmed the fracture healing. The in vitro study using pre-osteoblastic MC3T3-E1 cells demonstrated that NTAPP irradiation under specific conditions did not reduce cell proliferation but did enhance osteoblastic differentiation. Overall, these results suggest that NTAPP is a novel approach to the treatment of bone fractures.

Copyright: © 2024 Saito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

Animals
Cell Differentiation
Cell Proliferation
Femoral Fractures* / surgery
Fracture Healing
Fractures, Bone*
Plasma Gases* / pharmacology
Plasma Gases* / therapeutic use
Rats

Substances

Plasma Gases

Grants and funding

This work was supported by JSPS KAKENHI number JP19K03811 and the Glocal hub of wisdom and wellness filled with smiles. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Initial of the authors who received JSPS KAKENHI: JO URL: https://www.jsps.go.jp/j-grantsinaid/ Initial of the authors who received the Glocal hub of wisdom and wellness filled with smiles: HT.