title: Effect of a nonthermal-atmospheric pressure plasma jet on wound healing: An animal study.
abstract: BACKGROUND
  The use of a nonthermal plasma (NTP) jet in the treatment of living tissue has been the subject of considerable interest in the field of medical technology, and has the potential to reduce the recovery time of open wounds. We aimed to investigate the wound-healing process by clinical observation, blood tests, and expression of cell adhesion markers and reactive oxygen species in NTP jet-treated rats.
  
  
  METHODS
  This study utilized Sprague-Dawley (SD) rats as experimental subjects, and wounds measuring 2 cm × 2 cm were produced on the animals' backs. The experimental group was treated with NTP for 5 min/d for 4 weeks. The NTP was injected in a diffused manner into the cage housing the rats. The SD rats that had not received plasma treatment were designated as the control group. Blood was drawn on Postoperative Day 2, Day 4, and at 3 months. An immunohistochemical stain of E-cadherin and 4-hydroxy-2-nonenal (4-HNE), a reactive oxygen species marker, were evaluated and quantified for analysis using a CMYK color model.
  
  
  RESULTS
  A total of 35 SD rats were included in the study (25 in the NTP group and 10 in the control group). Low dose plasma treatment shortened the wound-healing time without damaging organs. In the NTP group, the white blood cell counts at Day 2 post-NTP treatment was not increased significantly more than that in the control group. After quantification of immunohistochemical staining, 4-HNE was increased at Day 14 compared with Day 7 (16.16 ± 12.81% vs. 55.11 ± 8.11%, p < 0.001), and E-cadherin was also increased (52.17 ± 14.96% vs. 70.46 ± 12.78%, p = 0.04) in the NTP group. After comparison of NTP and the control, it was observed that 4-HNE and E-cadherin were increased in the NTP group on Day 14.
  
  
  CONCLUSIONS
  Short-term, low-dose NTP wound treatment was demonstrated to accelerate wound healing in SD rats without vital organ toxicity.
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan, ROC; Department of Medicine Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Hung
authors.affiliation: Department of Stomatology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
authors.forename: Li-Tzu
authors.initials: LT
authors.lastname: Lee
authors.affiliation: Division of Gastroenterology, Taichung Veterans General Hospital, Taichung and School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Yen-Chun
authors.initials: YC
authors.lastname: Peng
authors.affiliation: Department of Stomatology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
authors.forename: Chiou-Tuz
authors.initials: CT
authors.lastname: Chang
authors.affiliation: Show Chwan Memorial Hospital, Chang Hwa, Taiwan, ROC; School of Dentistry, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Yong-Kie
authors.initials: YK
authors.lastname: Wong
authors.affiliation: College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan, ROC. Electronic address: kctung1234@gmail.com.
authors.forename: Kwong-Chung
authors.initials: KC
authors.lastname: Tung
mesh_terms: D000447:Aldehydes / Q000032:analysis; D000818:Animals; D015820:Cadherins / Q000032:analysis; D007150:Immunohistochemistry; D007958:Leukocyte Count; D058626:Plasma Gases; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing
chemical_list: D000447:Aldehydes; D015820:Cadherins; D058626:Plasma Gases; C027576:4-hydroxy-2-nonenal
keywords: 4-hydroxy-2-nonenal; E-cadherin; nonthermal plasma; wound healing