Rao Sowmya, Surya Suprith, S R Pavan, Ali Saheb, Prabhu Ashwini, Ginjupalli Kishore, Shenoy Pooja Umesh, Das Ranajit, B T Nandish
Reader, Department of Dental Materials, Yenepoya Dental College, Yenepoya (Deemed to be University), Mangalore 575018, Karnataka, India.
Consultant Veterinary Surgeon, Advanced Surgical Skill Enhancement Division (ASSEND), Yenepoya (Deemed to be University), Mangalore 575018, Karnataka, India.
J Prosthet Dent. 2024 Sep;132(3):644.e1-644.e10. doi: 10.1016/j.prosdent.2024.06.014. Epub 2024 Jul 27.
Quaternary ammonium (QA)-based monomers such as dimethyl-hexadecyl-methacryloxyethyl-ammonium iodide (DHMAI) and 2-dimethyl-2-dodecyl-1-methacryloxyethyl ammonium iodine (DDMAI) have been investigated as copolymerizable monomers to impart antimicrobial activity to dental restorative and prosthetic materials. However, the biocompatibility of these antimicrobial monomers needs to be investigated in vivo before their clinical use.
The purpose of this study was to assess the in vivo biocompatibility of polymethyl methacrylate (PMMA) heat-polymerizing denture base resin copolymerized with varying concentrations of DHMAI and DDMAI.
The toxicity and genotoxicity of the antimicrobial monomers (DHMAI 5 µg/mL and DDMAI 20 µg/mL) at 1 to 100 µg/mL concentrations were investigated against zebrafish embryos (Danio rerio, n=10) using a zebrafish embryotoxicity test (ZET) or fish embryotoxicity test (FET) and comet assay, respectively. Further, DHMAI 5 µg/mL and DDMAI 20 µg/mL were incorporated into a conventional PMMA denture base system and a similar test was done on specimens of modified PMMA resin. For the evaluation of in vivo biocompatibility, modified PMMA specimens were subcutaneously implanted into Wistar rats (n=6) and biochemical, hematological, and histopathological parameters were investigated. Results were analyzed and compared using ANOVA and the Tukey post hoc test (α=.05).
Toxicity and genotoxicity studies using zebrafish embryos revealed that the incorporation of monomer to PMMA did not increase the toxicity, as confirmed by post-hour fertilization. Modified PMMA did not affect the hematological parameters, such as red blood cell (RBC) and white blood cell (WBC) except for the platelet count, which was significantly increased (P<.001), and the biochemical parameter, such as total protein (TP), blood urea nitrogen (BUN), serum glutamic-oxaloacetic transaminase (SGOT), triglyceride (TG), creatinine (Crea), total cholesterol, and serum glutamic pyruvic transaminase (SGPT), except for high-density lipoprotein (HDL) cholesterol, which was significantly decreased (P<.01). Histopathologically, no changes were observed in the sections of the liver, kidney, spleen, and subcutaneous tissues in the modified PMMA implanted rats. Additionally, no significant variation was found in the expression of immunohistochemical marker tumor necrosis factor alpha (TNF-α), confirming the noninflammatory response exerted by the modified PMMA on experimental rats.
Zebrafish embryos treated with modified PMMA specimens demonstrated favorable biological properties and did not exhibit significant cytotoxicity and genotoxicity. Subcutaneously implanted modified PMMA did not cause any major hematological, biochemical, and histopathological alterations in Wistar albino rats, thus confirming the biocompatibility of PMMA heat-polymerizing denture base resin incorporated with DHMAI and DDMAI for dental applications.
基于季铵(QA)的单体,如甲基丙烯酰氧乙基十六烷基二甲基碘化铵(DHMAI)和甲基丙烯酰氧乙基二甲基十二烷基碘化铵(DDMAI),已作为可共聚单体进行研究,以赋予牙科修复和假体材料抗菌活性。然而,这些抗菌单体的生物相容性在临床应用前需要进行体内研究。
本研究的目的是评估与不同浓度的DHMAI和DDMAI共聚的聚甲基丙烯酸甲酯(PMMA)热聚合义齿基托树脂的体内生物相容性。
分别使用斑马鱼胚胎毒性试验(ZET)或鱼类胚胎毒性试验(FET)以及彗星试验,研究浓度为1至100μg/mL的抗菌单体(DHMAI 5μg/mL和DDMAI 20μg/mL)对斑马鱼胚胎(Danio rerio,n = 10)的毒性和遗传毒性。此外,将DHMAI 5μg/mL和DDMAI 20μg/mL加入传统的PMMA义齿基托系统中,并对改性PMMA树脂标本进行类似试验。为了评估体内生物相容性,将改性PMMA标本皮下植入Wistar大鼠(n = 6)体内,并研究生化、血液学和组织病理学参数。使用方差分析和Tukey事后检验(α = 0.05)对结果进行分析和比较。
使用斑马鱼胚胎进行的毒性和遗传毒性研究表明,如受精后数小时所证实,单体与PMMA的结合并未增加毒性。改性PMMA除了血小板计数显著增加(P < 0.001)外,对红细胞(RBC)和白细胞(WBC)等血液学参数没有影响,对总蛋白(TP)、血尿素氮(BUN)、血清谷草转氨酶(SGOT)、甘油三酯(TG)、肌酐(Crea)、总胆固醇和血清谷丙转氨酶(SGPT)等生化参数也没有影响,但高密度脂蛋白(HDL)胆固醇显著降低(P < 0.01)。组织病理学上,在植入改性PMMA的大鼠的肝脏、肾脏、脾脏和皮下组织切片中未观察到变化。此外,免疫组化标志物肿瘤坏死因子α(TNF-α)的表达没有显著差异,证实了改性PMMA对实验大鼠没有产生炎症反应。
用改性PMMA标本处理的斑马鱼胚胎表现出良好的生物学特性,没有表现出明显的细胞毒性和遗传毒性。皮下植入的改性PMMA在Wistar白化大鼠中未引起任何主要的血液学、生化和组织病理学改变,从而证实了与DHMAI和DDMAI结合的PMMA热聚合义齿基托树脂在牙科应用中的生物相容性。