Departamento de Ortopedia e Traumatologia, Escola Paulista de Medicina/UNIFESP, Universidade Federal de São Paulo, Rua Borges Lagoa 783, 5° andar, São Paulo, Brazil.
Center for Regenerative Medicine and Cartilage Repair Center, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, USA.
Knee Surg Sports Traumatol Arthrosc. 2019 Mar;27(3):931-935. doi: 10.1007/s00167-017-4746-9. Epub 2017 Nov 8.
The objective of this study was to evaluate potential cytotoxicity of TXA on articular cartilage by assessing chondrocyte viability of osteochondral explants after exposure to different concentrations and durations of TXA.
Thirty-nine osteochondral plugs (OCPs) were harvested from three adult Yucatan minipigs immediately after their death. OCPs were divided into 13 groups exposed to different concentrations of TXA (1, 2 and 4 mg/ml in saline solution) for 1, 3 and 6 h. Negative controls were exposed to saline solution for 0, 1, 3 and 6 h. Chondrocyte viability was assessed by Live/Dead cell assay and calculated as the ratio of live cells (green fluorescence) to overall cells (green + red cells) for each concentration of TXA and time point in a 50-µm scanned image.
No correlation was found between chondrocyte viability, and TXA concentration and time of exposure. Overall, chondrocyte viability ranged from 90 to 99%. There was no statistical difference among control group, 1, 2 and 4 mg/ml TXA solutions at each time point [1 h (n.s.), 3 h (n.s.), 6 h (n.s.)]. Similarly, no statistical difference among groups was observed when comparing cell viability at 1, 3 and 6 h of TXA exposure, (Fig. 2) [1 mg/ml (n.s.), 2 mg/ml (n.s.), and 4 mg/ml (n.s.)].
In conclusion, doses of TXA approximating the current clinical protocols for topical use did not demonstrate any cytotoxic effects on cartilage explants in a Yucatan mini pig model. Thus, supporting the topical application for procedures with intact cartilage, such as partial knee replacement surgery and cartilage repair procedures.
本研究旨在通过评估不同浓度和时间的 TXA 暴露后骨软骨标本中软骨细胞的活力,评估 TXA 对关节软骨的潜在细胞毒性。
本研究共采集了 39 个来自成年尤卡坦微型猪的骨软骨标本。将标本分为 13 组,分别暴露于不同浓度的 TXA(生理盐水溶液中的 1、2 和 4mg/ml)1、3 和 6 小时。阴性对照组暴露于生理盐水溶液中 0、1、3 和 6 小时。通过 Live/Dead 细胞检测评估软骨细胞活力,并计算每个 TXA 浓度和时间点在 50µm 扫描图像中活细胞(绿色荧光)与总细胞(绿色+红色细胞)的比值。
软骨细胞活力与 TXA 浓度和暴露时间之间无相关性。总体而言,软骨细胞活力在 90%至 99%之间。在每个时间点,对照组、1、2 和 4mg/ml TXA 溶液之间均无统计学差异[1 小时(无统计学意义)、3 小时(无统计学意义)、6 小时(无统计学意义)]。同样,当比较 TXA 暴露 1、3 和 6 小时时各组之间的细胞活力时,也未观察到统计学差异[1mg/ml(无统计学意义)、2mg/ml(无统计学意义)和 4mg/ml(无统计学意义)]。
总之,接近目前临床局部应用方案的 TXA 剂量在尤卡坦微型猪模型中未显示出对软骨标本的任何细胞毒性作用。因此,支持在具有完整软骨的手术中局部应用,如部分膝关节置换术和软骨修复术。