A new drug testing platform based on 3D tri-culture in lab-on-a-chip devices.

Drug discovery has a 90% rate of failure because preclinical platforms for drug testing do not mimic the in vivo conditions. Doxorubicin (DOX) is a commonly used drug to treat breast cancer patients even though it has side effects. Lab-on-a-chip (LOC) devices provide spatial control at the micrometer scale and can thus emulate the cancer microenvironment. Here, using a multidisciplinary approach, a new drug testing platform based on 3D tri-culture in LOC devices was developed. Breast cancer cells alone or with normal mammary epithelial cells and macrophages were cultured in matrigel in LOC devices. The platform was used to test DOX and (R)-4'-methylklavuzon (KLA), which is a new anti-cancer drug candidate. Results showed that DOX and KLA were equally effective on breast cancer cells in 3D monoculture. KLA produced 26% less death for breast cancer cells than DOX in 3D tri-culture. More importantly, DOX was not selective between breast cancer cells and normal mammary epithelial cells in 3D tri- culture whereas KLA caused 56% less cell death than DOX for normal mammary epithelial cells. Results strongly recommend that 3D tri-culture in LOC devices be used for assessment of drug toxicity at the preclinical stage.

Periodontal effects and survival rates of different mandibular retainers: comparison of bonding technique and wire thickness.

OBJECTIVES: This non-randomized prospective cohort study aimed to compare the periodontal effects and success rates of mandibular canine-to-canine fixed retainers having different bonding techniques and wire thicknesses. MATERIALS AND METHODS: Hundred patients requiring retention after orthodontic treatment were assigned to five study groups (n = 20 in each group, 61 females/39 males, median age range 16.5-18.0 years). Retention was provided by 0.0215"/direct, 0.0215"/indirect, 0.0175"/direct, 0.0175"/indirect bonded multistranded wires and removable Essix appliances. The primary and secondary outcomes were periodontal effects and success rates. The patients were examined in 1 week, 1 month, 3 months and 6 months follow-up appointments. Plaque index, gingival index, probing depth, marginal recession, bleeding on probing, failure rate per retainer wire and survival of retainer wires were analysed by Kruskal-Wallis H, Mann-Whitney U and chi-square tests. RESULTS: Significant differences were observed between the fixed retainer (FR) and Essix (E) groups in gingival index scores at 1 month [mean FR: 1.13 (95% confidence interval (CI): 0.81-1.44), mean E: 0.40 (95% CI: 0.14-0.69), mean difference: 0.73, P < 0.01], 3 months [mean FR: 0.97/1.01 (95% CI: 0.65-1.30/0.72-1.30), mean E: 0.52 (95% CI: 0.25-0.82), mean differences: 0.45/0.49, P < 0.05], 6 months [mean FR: 0.94 (95% CI: 0.62-1.27), mean E: 0.35 (95% CI: 0.15-0.58), mean difference: 0.59, P < 0.05] and in bleeding on probing scores at 1 month [mean FR: 3.05 (95% CI: 2.12-3.98), mean E: 1.15 (95% CI: 0.42-1.88), mean difference: 1.90, P < 0.01]. The survival rates of retainer wires were 85 per cent for the 0.0215" direct/indirect and 90 per cent for the 0.0175" direct/indirect groups for the 6 months follow-up. LIMITATIONS: Six months follow-up period, which demonstrates only short-term outcomes. CONCLUSIONS: The periodontal outcomes or survival rates of mandibular fixed retainers were not affected by bonding technique or wire thickness, whereas gingival health improved with Essix retainers but not with fixed retainers.