Faculty of Medical and Heath Sciences, University of Auckland, Auckland, New Zealand.
Department of Orthopaedic Surgery, Auckland City Hospital, Auckland, New Zealand.
J Orthop Surg Res. 2022 May 15;17(1):273. doi: 10.1186/s13018-022-03167-5.
Tranexamic acid (TXA) has been shown to be effective at reducing peri-operative blood loss and haemarthrosis in arthroplasty and arthroscopic soft tissue reconstructions. Intra-articular application, as an injection or peri-articular wash, is becoming increasingly common. Recent studies have shown TXA has the potential to be cytotoxic to cartilage, but its effects on human tendon and bone remain poorly understood. The aim of this study was to investigate whether TXA has any detrimental effects on tendon-derived cells and osteoblast-like cells and determine whether there is a safe dosage for clinical application.
Primary tendon-derived cells and osteoblast-like cells were harvested from hamstring tendons and trabecular bone explants, respectively, and analysed in vitro with a range of TXA concentrations (0 to 100 mg/ml) at time points: 3 and 24 h. The in vitro toxic effect of TXA was investigated using viability assays (alamarBlue), functional assays (collagen deposition), fluorescent microscopy and live/apoptosis/necrosis staining for cell death mechanisms in 2D monolayer and 3D collagen gel cell culture.
There was a significant (P < 0.05) decrease in tendon-derived cell and osteoblast-like cell numbers following treatment with TXA ≥ 50 mg/ml after 3 h and ≥ 20 mg/ml after 24 h. In tendon-derived cells, increasing concentrations > 35 mg/ml resulted in significantly (P < 0.05) reduced collagen deposition. Fluorescence imaging confirmed atypical cellular morphologies with increasing TXA concentrations and reduced cell numbers. The mechanism of cell death was demonstrated to be occurring through apoptosis.
Topical TXA treatment demonstrated dose- and time-dependent cytotoxicity to tendon-derived cells and osteoblast-like cells with concentrations 20 mg/ml and above in isolated 2D and 3D in vitro culture. On the basis of these findings, concentrations of less than 20 mg/ml are expected to be safe. Orthopaedic surgeons should show caution when considering topical TXA treatments, particularly in soft tissue and un-cemented arthroplasty procedures.
氨甲环酸（TXA）已被证明可有效减少关节置换和关节镜下软组织重建术中的围手术期失血和关节积血。关节内应用，如注射或关节周围冲洗，越来越普遍。最近的研究表明，TXA 有可能对软骨产生细胞毒性，但它对人肌腱和骨骼的影响仍知之甚少。本研究旨在探讨 TXA 是否对肌腱源性细胞和成骨样细胞有任何不良影响，并确定其临床应用的安全剂量。
从半腱肌腱和小梁骨外植体中分别采集原代肌腱源性细胞和成骨样细胞，并在时间点：3 和 24 h 时，用一系列 TXA 浓度（0 至 100 mg/ml）进行体外分析。TXA 的体外毒性作用通过活力测定（alamarBlue）、功能测定（胶原蛋白沉积）、荧光显微镜和细胞死亡机制的活/凋亡/坏死染色进行研究，用于 2D 单层和 3D 胶原凝胶细胞培养。
TXA 治疗后 3 h，TXA≥50 mg/ml，24 h，TXA≥20 mg/ml，肌腱源性细胞和成骨样细胞数量明显减少（P<0.05）。在肌腱源性细胞中，浓度>35 mg/ml 会导致胶原蛋白沉积显著减少（P<0.05）。荧光成像证实，随着 TXA 浓度的增加，细胞形态发生异常，细胞数量减少。细胞死亡的机制被证明是通过凋亡发生的。
局部 TXA 治疗对肌腱源性细胞和成骨样细胞具有剂量和时间依赖性细胞毒性，在离体 2D 和 3D 体外培养中浓度为 20 mg/ml 及以上。基于这些发现，浓度低于 20 mg/ml 预计是安全的。骨科医生在考虑局部 TXA 治疗时应谨慎，特别是在软组织和非骨水泥关节置换手术中。
