Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Baskent University, Bahçelievler 11. Sokak no:26 Mareşal Fevzi Çakmak Caddesi Çankaya, 06490, Ankara, Turkey.
Department of Medical Biology, Faculty of Medicine, Baskent University, Ankara, Turkey.
Clin Oral Investig. 2018 Mar;22(2):867-873. doi: 10.1007/s00784-017-2163-6. Epub 2017 Jul 11.
Medication-related osteonecrosis of the jaws (MRONJ) is an extremely therapy-resistant disease involving the jaws especially following bisphosphonate treatment. Bisphosphonates accumulate in bone in concentrations sufficient to be directly toxic to the oral epithelium. Current therapeutic options are inadequate for the prevention and treatment of MRONJ. The aim of this study was to investigate effects of ozone gas plasma therapy on wound healing in bisphosphonate-applied human fibroblasts.
Human primary gingival fibroblasts were cultured. Cytotoxic concentrations (IC50) of bisphosphonates (pamidronate (PAM), alendronate (ALN), and zoledronate (ZOL)) were determined by MTT test. A 60 μg/μl for 30 s of ozone gas plasma application was performed to all experimental culture flasks after drug treatment at 24-h intervals as 3 s/cm. Genotoxic damages were evaluated by comet assay and wound healing was determined by in vitro scratch assay.
PAM, ALN, and ZOL applications caused genotoxic damage on primary human gingival fibroblast DNA. Ozone gas plasma therapy significantly decreased the genotoxic damage (p < 0.05), and this application provided 25, 29, and 27% less genotoxic damage in order of ALN, PAM, and ZOL groups. Ozone gas plasma therapy significantly increased wound healing rates both in postsurgical 24th and 48th hours for all doses of experimental drug groups (p < 0.05).
The ozone gas plasma application decreased genotoxic damage effect of bisphosphonate usage while improved the wound closure rate on human gingival fibroblasts.
Ozone gas plasma therapy may be helpful in prevention of gingival healing delay in MRONJ pathogenesis especially when applied simultaneously with surgical intervention.
药物相关性颌骨坏死（MRONJ）是一种极其难以治疗的疾病，尤其是在接受双膦酸盐治疗后，颌骨会受到影响。双膦酸盐在骨骼中积聚的浓度足以对口腔上皮产生直接毒性。目前的治疗选择对于预防和治疗 MRONJ 是不够的。本研究旨在探讨臭氧气体等离子体治疗对应用双膦酸盐的人成纤维细胞伤口愈合的影响。
培养人原代牙龈成纤维细胞。通过 MTT 试验确定双膦酸盐（帕米膦酸盐（PAM）、阿仑膦酸盐（ALN）和唑来膦酸盐（ZOL））的细胞毒性浓度（IC50）。在药物治疗后 24 小时，对所有实验组培养瓶进行 60μg/μl 臭氧气体等离子体处理 30 秒，处理间隔为 3s/cm。通过彗星试验评估遗传毒性损伤，通过体外划痕试验确定伤口愈合情况。
PAM、ALN 和 ZOL 的应用导致原代人牙龈成纤维细胞 DNA 发生遗传毒性损伤。臭氧气体等离子体治疗显著降低了遗传毒性损伤（p<0.05），按 ALN、PAM 和 ZOL 组的顺序，这种治疗分别减少了 25%、29%和 27%的遗传毒性损伤。臭氧气体等离子体治疗显著增加了所有实验组在手术后 24 小时和 48 小时的伤口愈合率（p<0.05）。
臭氧气体等离子体应用降低了双膦酸盐使用的遗传毒性损伤效应，同时提高了人牙龈成纤维细胞的伤口闭合率。
臭氧气体等离子体治疗可能有助于预防 MRONJ 发病机制中的牙龈愈合延迟，特别是在与手术干预同时应用时。
