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. 2022 Dec 1;28(12):2633–2645. doi: 10.1038/s41591-022-02059-9

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 4 — Data are analyzed using a linear mixed-effect model with repeated measures. The two-sided P-value was obtained by t-statistic. a, LNA043 staining detected only in cohort 5 samples from the CLNA043X2101 study, when LNA043 was injected 2 h before TKR. Individual data points and boxplot of the LNA043 staining score of osteochondral samples from all cohorts are shown. Positive staining was observed in cohort 5 (*P = 0.0002). Boxplot data is expressed as median and lower/upper quartiles and whiskers at 1.5 times the interquartile range. b, LNA043 diffuses deeper into damaged compared to undamaged cartilage. Scatter plot of LNA043 penetration depth in cartilage samples from cohort 5, expressed as % of cartilage thickness, which is positively stained. Measurements were performed by an expert pathologist (KAW) on n=11 samples, with 4 samples harvested from different areas of the knee (osteochondral biopsies from femoral condyle, patella, trochlea, tibia) for each of the 3 patients (1 sample missing, because there was no cartilage left). Dotted lines separate data from individual patients. P = 0.000000475 for LNA043 penetration depth in damaged compared to undamaged cartilage.