In innervated collagenous tissues, tissue scale loading may contribute to joint pain by transmitting force through collagen fibers to the embedded mechanosensitive axons. However, the highly heterogeneous collagen structures of native tissues make understanding this relationship challenging. Recently, collagen gels with embedded axons were stretched and the resulting axon signals were measured, but these experiments were unable to measure the local axon strain fields. Computational discrete fiber network models can directly determine axon strain fields due to tissue scale loading. Therefore, this study used a discrete fiber network model to identify how heterogeneous collagen networks (networks with multiple collagen fiber densities) change axon strain due to tissue scale loading. In this model, a composite cylinder (axon) was embedded in a Delaunay network (collagen). Homogeneous networks with a single collagen volume fraction and two types of heterogeneous networks with either a sparse center or dense center were created. Measurements of fiber forces show higher magnitude forces in sparse regions of heterogeneous networks and uniform force distributions in homogeneous networks. The average axon strain in the sparse center networks decreases when compared to homogeneous networks with similar collagen volume fractions. In dense center networks, the average axon strain increases compared to homogeneous networks. The top 1% of axon strains are unaffected by network heterogeneity. Based on these results, the interaction of tissue scale loading, collagen network heterogeneity, and axon strains in native musculoskeletal tissues should be considered when investigating the source of joint pain.

在受神经支配的胶原组织中，组织鳞负荷可能通过胶原纤维将力传递到嵌入的机械敏感轴突而导致关节疼痛。然而，天然组织的高度异质胶原蛋白结构使得理解这种关系具有挑战性。最近，拉伸嵌入轴突的胶原凝胶并测量所得的轴突信号，但这些实验无法测量局部轴突应变场。计算离散纤维网络模型可以直接确定由于组织尺度负载而产生的轴突应变场。因此，本研究使用离散纤维网络模型来确定异质胶原网络（具有多种胶原纤维密度的网络）如何因组织尺度负载而改变轴突应变。在此模型中，复合圆柱体（轴突）嵌入 Delaunay 网络（胶原蛋白）中。创建了具有单一胶原体积分数的同质网络和具有稀疏中心或密集中心的两种类型的异质网络。纤维力的测量显示异构网络的稀疏区域中的力值较高，而同质网络中的力分布均匀。与具有相似胶原体积分数的均匀网络相比，稀疏中心网络中的平均轴突应变降低。在密集的中心网络中，与同质网络相比，平均轴突应变增加。前 1% 的轴突菌株不受网络异质性的影响。基于这些结果，在研究关节疼痛的根源时，应考虑组织尺度负荷、胶原网络异质性和天然肌肉骨骼组织中轴突应变的相互作用。