Six-Month Outcomes of Clinically Relevant Meniscal Injury in a Large-Animal Model.

Six-Month Outcomes of Clinically Relevant Meniscal Injury in a Large-Animal Model.
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DOI:
10.1177/23259671211035444
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发表时间:
2021-11
影响因子:
2.6
通讯作者:
Mauck RL
Mauck RL
中科院分区:
医学3区
文献类型:
--
作者:
Bansal S;Meadows KD;Miller LM;Saleh KS;Patel JM;Stoeckl BD;Lemmon EA;Hast MW;Zgonis MH;Scanzello CR;Elliott DM;Mauck RL

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半月板损伤的矫正程序取决于撕裂类型、严重程度和位置。垂直纵向撕裂在年轻且活跃的个体中较为常见,但其自然进展以及对骨关节炎(OA)发展的影响尚不明确。根部撕裂具有挑战性,通常预示着不良结果,尽管关节功能障碍起始的时间和机制了解甚少,在大型动物和人体模型中尤其如此。 在这项研究中,在大型动物模型中制造了垂直纵向撕裂和根部撕裂,以确定全关节功能障碍的进展。我们假设骨关节炎的发作和进展将取决于组织中基于损伤的负荷破坏程度,因此根部撕裂会对关节造成更早且更严重的变化。 对照实验室研究。 通过随机双侧关节镜手术,在尤卡坦小型幼猪身上进行假手术以及制造垂直纵向撕裂或根部撕裂的手术。在损伤后1个月、3个月或6个月处死动物,并在关节和组织层面评估骨关节炎的迹象。进行了关节负荷传递、软骨压痕力学和半月板拉伸性能的功能测量,以及对软骨、半月板和滑膜的组织学评估。 结果表明,根部撕裂后膝关节和半月板逐渐且持续退变,软骨和半月板的组织学分析证明了这一点。尽管根部有自发重新附着,但仍发生了这种情况,这表明这种重新附着未能完全恢复原生附着的功能。相比之下,垂直纵向撕裂未对关节造成显著变化,在6个月时间点与假手术相比仅有轻微差异。 鉴于切断周向连接和负荷传递的根部撕裂与周向稳定的垂直纵向撕裂相比导致更严重的骨关节炎,我们的研究结果表明,如果没有及时且力学上有效的固定,根部撕裂可能会导致不可逆的关节损伤。 更广泛地说,这种新模型可作为损伤后实验性手术、基于支架以及小分子驱动干预措施的试验台,以防止骨关节炎进展。
The corrective procedures for meniscal injury are dependent on tear type, severity, and location. Vertical longitudinal tears are common in young and active individuals, but their natural progression and impact on osteoarthritis (OA) development are not known. Root tears are challenging and they often indicate poor outcomes, although the timing and mechanisms of initiation of joint dysfunction are poorly understood, particularly in large-animal and human models. In this study, vertical longitudinal and root tears were made in a large-animal model to determine the progression of joint-wide dysfunction. We hypothesized that OA onset and progression would depend on the extent of injury-based load disruption in the tissue, such that root tears would cause earlier and more severe changes to the joint. Controlled laboratory study. Sham surgeries and procedures to create either vertical longitudinal or root tears were performed in juvenile Yucatan mini pigs through randomized and bilateral arthroscopic procedures. Animals were sacrificed at 1, 3, or 6 months after injury and assessed at the joint and tissue level for evidence of OA. Functional measures of joint load transfer, cartilage indentation mechanics, and meniscal tensile properties were performed, as well as histological evaluation of the cartilage, meniscus, and synovium. Outcomes suggested a progressive and sustained degeneration of the knee joint and meniscus after root tear, as evidenced by histological analysis of the cartilage and meniscus. This occurred in spite of spontaneous reattachment of the root, suggesting that this reattachment did not fully restore the function of the native attachment. In contrast, the vertical longitudinal tear did not cause significant changes to the joint, with only mild differences compared with sham surgery at the 6-month time point. Given that the root tear, which severs circumferential connectivity and load transfer, caused more intense OA compared with the circumferentially stable vertical longitudinal tear, our findings suggest that without timely and mechanically competent fixation, root tears may cause irreversible joint damage. More generally, this new model can serve as a test bed for experimental surgical, scaffold-based, and small molecule–driven interventions after injury to prevent OA progression.
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