Reversible changes in the 3D collagen fibril architecture during cyclic loading of healthy and degraded cartilage.
Reversible changes in the 3D collagen fibril architecture during cyclic loading of healthy and degraded cartilage.
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DOI：
10.1016/j.actbio.2021.09.037
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发表时间：
2021-12
影响因子：
9.7
通讯作者：
Gupta HS
中科院分区：
文献类型：
--
作者：
Inamdar SR;Prévost S;Terrill NJ;Knight MM;Gupta HS
关节软骨中胶原纤维结构的生物力学变化被认为在正常关节功能中起着至关重要的作用。然而，关于软骨中II型胶原原纤维对原位循环载荷的结构反应，以及驱动软骨承受长期重复载荷能力的机制，在实验上几乎没有定量的知识。在这里，我们利用同步加速器小角度x射线散射（SAXS）结合原位循环加载牛关节软骨外植体来测量关节软骨深部区的纤维反应，包括健康软骨和暴露于促炎细胞因子IL-1β下降解的软骨的取向、纤维应变和纤维间变异性。我们证明，在重复的循环载荷下，原纤维可逆地改变了原纤维取向分布的宽度，同时保持了基本一致的平均取向方向。具体来说，通过对二维模式的x射线散射峰强度分布进行三维重建推断，对纤维网络的影响是围绕法线向节理面扩展的三维锥形取向。此外，在纤维内水平，这种效应伴随着压缩下纤维预应变的可逆减少，以及纤维预应变变异性的增加。在IL-1β降解的软骨中，胶原蛋白在循环载荷下的重排被破坏，并与组织刚度降低有关。这些发现暗示了局部胶原纳米力学的变化如何推动疾病进展，反之亦然，在骨关节炎等疾病中，并提供了对此类疾病的机制理解的途径。生物力学负荷的肌肉骨骼器官的结构恶化，如关节骨关节炎和背痛，与富含胶原的软骨组织基质的破坏和变化有关。软骨中的超微结构胶原纤维网络是软骨生物力学的关键组成部分。然而，软骨胶原蛋白对生物力学载荷的动态结构响应的实验探针是有限的。在这里，我们使用x射线散射在循环加载期间（如在行走期间）对关节组织表明，软骨原纤维在分子水平上通过可逆的，三维定向扩大和无序机制抵抗加载，炎症降低了这种功能。我们的研究结果将有助于理解小规模组织机制的变化如何与衰老和骨关节炎的进展以及关节置换生物材料的发展联系在一起。
Biomechanical changes to the collagen fibrillar architecture in articular cartilage are believed to play a crucial role in enabling normal joint function. However, experimentally there is little quantitative knowledge about the structural response of the Type II collagen fibrils in cartilage to cyclic loading in situ, and the mechanisms that drive the ability of cartilage to withstand long-term repetitive loading. Here we utilize synchrotron small-angle X-ray scattering (SAXS) combined with in-situ cyclic loading of bovine articular cartilage explants to measure the fibrillar response in deep zone articular cartilage, in terms of orientation, fibrillar strain and inter-fibrillar variability in healthy cartilage and cartilage degraded by exposure to the pro-inflammatory cytokine IL-1β. We demonstrate that under repeated cyclic loading the fibrils reversibly change the width of the fibrillar orientation distribution whilst maintaining a largely consistent average direction of orientation. Specifically, the effect on the fibrillar network is a 3-dimensional conical orientation broadening around the normal to the joint surface, inferred by 3D reconstruction of X-ray scattering peak intensity distributions from the 2D pattern. Further, at the intrafibrillar level, this effect is coupled with reversible reduction in fibrillar pre-strain under compression, alongside increase in the variability of fibrillar pre-strain. In IL-1β degraded cartilage, the collagen rearrangement under cyclic loading is disrupted and associated with reduced tissue stiffness. These finding have implications as to how changes in local collagen nanomechanics might drive disease progression or vice versa in conditions such as osteoarthritis and provides a pathway to a mechanistic understanding of such diseases. Structural deterioration in biomechanically loaded musculoskeletal organs, e.g., joint osteoarthritis and back pain, are linked to breakdown and changes in their collagen-rich cartilaginous tissue matrix. A critical component enabling cartilage biomechanics is the ultrastructural collagen fibrillar network in cartilage. However, experimental probes of the dynamic structural response of cartilage collagen to biomechanical loads are limited. Here, we use X-ray scattering during cyclic loading (as during walking) on joint tissue to show that cartilage fibrils resist loading by a reversible, three-dimensional orientation broadening and disordering mechanism at the molecular level, and that inflammation reduces this functionality. Our results will help understand how changes to small-scale tissue mechanisms are linked to ageing and osteoarthritic progression, and development of biomaterials for joint replacements.
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