Luiz Felipe Ambra1,2, Laura de Girolamo3, Wanting Niu4,5, Amy Phan6, Myron Spector4,5, Andreas H Gomoll6,5. 1. Departamento de Ortopedia e Traumatologia, Escola Paulista de Medicina/UNIFESP, Universidade Federal de São Paulo, Rua Borges Lagoa 783, 5° andar, São Paulo, Brazil. felipeambra71@gmail.com. 2. Center for Regenerative Medicine and Cartilage Repair Center, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, USA. felipeambra71@gmail.com. 3. Orthopedic Biotechnology Laboratory, Galeazzi Orthopaedic Institute, Milan, Italy. 4. Tissue Engineering Labs, VA Boston Healthcare System, Boston, MA, USA. 5. Department of Orthopedics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 6. Center for Regenerative Medicine and Cartilage Repair Center, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, USA.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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.)]. CONCLUSIONS: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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.)]. CONCLUSIONS: 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.
Authors: Benjamin Jacob; Nadja Kloss; Sabrina Böhle; Julia Kirschberg; Timo Zippelius; Markus Heinecke; Georg Matziolis; Eric Röhner Journal: J Orthop Date: 2019-12-19
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