## 4 Discussion
In comparing the simulated cases between the different deformation regimes, the degradation of the crosslinks content decreased the range of the elasticity of the ACL significantly. For example, an almost 50% decrease in elastic strain capacity has been observed between the native and fully degraded fibrils. At very low crosslink content (0 to 20%), the ACL lost the typical stress-strain behavior in which the three different regimes of deformation before the failure can be observed [23]. Here, the ACL behavior switched directly from the gradual transition regime to the failure regime, ignoring the linear regime (Figure 5). Direct comparison with published studies is difficult due to differences in ACL geometry/constitutive formulation and the parameters examined. The general mechanical behavior of the ACL model reported here, where the crosslinks content ranged from 80 to 100%, is very similar to that of [PERSON] et al. [62] and [PERSON] [63], where the estimated tangent modulus, tensile strength, and the ultimate strain fall in their reported range of measurements. In the fully crosslinked fibril, the elastic stress distribution of the ACL reached its peak of 22 MPa near the tibial junction at 7.5% of axial strain (Figure 7). However, this stress dwindled in magnitude and distribution by almost 50% with degradation of the collagen crosslinks. The stress concentration was located in the ACL posterolateral bundle in all simulated cases, an observation consistent with earlier published experiments [64; 65; 66]. The above results supported first the validity of the proposed model to predict the physiological stress of the ACL and the reported importance of the crosslinks content on the elasticity of the ligaments [22]. An alteration of this content may clearly affect the principal role of the ACL in preventing laxity or stiffness of the kinematics of the knee joint during human activities [67]. The ACL yield strength and strain were influenced by the degradation of the enzymatical crosslinks (Figure 6). The range of the stiffness of the ligament decreased significantly with the decrease in the crosslink content, owing to the relative diminution of the yield stress. These results support the earlier-reported positive correlations between crosslinks content and ligament strength [20; 68]. The current prediction showed that the spatial distribution of the macro-damage also depended on the crosslinks content (Figure 8). The degradation of the enzymatical crosslinks substantially contributed to explaining the damage patterns (plastic change). The plastic change covered most of the superficial layer of the ACL middle zone with the absence of any crosslinks between the TC molecules. At the same time, a mature structure of the collagen fibril led to a very limited area of ACL damage. The predicted damage patterns from the proposed model in the current investigation are in line with previously reported ACL-failure patterns [69; 70; 71; 72; 73]. These studies have shown a mixed mode of failures occurring at the mid-substance and near the ligaments-bone junction. These results clearly endorse the validity of the proposed computational frame in predicting aggregate mechanical damage of the ACL using a combined formula between molecular dynamics and finite-element simulations. Hence, this toolbox could be used to study some clinical aspects treating the female gender bias in ACL damage. Longitudinal studies have provided few clues about how altering sex hormones by modulating collagenases and gelatinase may lead to cleaving and denature the fibrillar collagen in the ACL before and after the menses period [74; 75; 76; 77]. However, it is unclear how the hormonally modulated enzymes act at the nano-scale, leading to visible damage to the aggregate collagen structures in the ACL. In addition, other collagen molecular defects, such as advanced glycation end-products (AGEs) and their effects on the aggregate mechanics of the ligament, could be targeted by the proposed frame [78].