Spierings Janne, van Doeselaar Marina, Buenen Mads, Abinzano Florencia, van der Steen Marieke, Janssen Rob, Ito Keita, Foolen Jasper
Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Department of Orthopaedic Surgery & Trauma, Máxima Medical Centre Eindhoven/Veldhoven, Eindhoven, The Netherlands.
Sci Rep. 2025 May 30;15(1):19091. doi: 10.1038/s41598-025-03788-w.
Anterior cruciate ligament (ACL) rupture requires reconstruction (ACLR), often using tendon autografts, to restore joint stability. However, postoperative issues persist, especially in younger patients, with the primary cause still unclear. These issues are believed to result from a detrimental in vivo remodeling response, characterized by macrophage-involving inflammation that is driven by dead and dying graft resident cells. This research aimed to (1) analyze factors secreted by different tendon grafts, (2) investigate how these factors influence macrophage polarization, and (3) explore the influence of patients' age on these secreted factors. An ex vivo set-up was used to provide new insights into the role of tendon grafts in the inflammatory response observed after ACLR in a patient-specific way. It was found that the dying cells in fresh autografts released a mixture of pro- and anti-inflammatory cytokines and matrix metalloproteinases. This release was reduced in grafts where the cells were already dead (frozen) or in grafts from which the cells were removed (decellularized). The release of pro-inflammatory cytokines by fresh grafts may contribute to the inflammatory response after ACLR. However, secreted factors did not polarize (THP-1) macrophages in our in vitro setup. A key finding of this study was the observed patient-specific response, which was not age-related in the used cohort, which emphasizes the need for personalized rehabilitation. In the future, correlating these findings with clinical patients' outcomes can enhance understanding of patient-specific recovery and aid in finding a biomarker for personalized rehabilitation.
前交叉韧带（ACL）断裂需要进行重建（ACLR），通常使用自体肌腱移植来恢复关节稳定性。然而，术后问题仍然存在，尤其是在年轻患者中，主要原因仍不清楚。这些问题被认为是由有害的体内重塑反应导致的，其特征是由死亡和即将死亡的移植驻留细胞驱动的涉及巨噬细胞的炎症。本研究旨在：（1）分析不同肌腱移植物分泌的因子；（2）研究这些因子如何影响巨噬细胞极化；（3）探讨患者年龄对这些分泌因子的影响。采用体外实验装置，以患者特异性的方式为肌腱移植物在ACLR后观察到的炎症反应中的作用提供新的见解。研究发现，新鲜自体移植物中的死亡细胞释放了促炎和抗炎细胞因子以及基质金属蛋白酶的混合物。在细胞已经死亡的移植物（冷冻）或细胞已被去除的移植物（脱细胞）中，这种释放减少。新鲜移植物中促炎细胞因子的释放可能导致ACLR后的炎症反应。然而，在我们的体外实验装置中，分泌因子并未使（THP-1）巨噬细胞极化。本研究的一个关键发现是观察到的患者特异性反应，在所使用的队列中与年龄无关，这强调了个性化康复的必要性。未来，将这些发现与临床患者的结果相关联，可以增强对患者特异性恢复的理解，并有助于找到个性化康复的生物标志物。
