## 4 Discussion  
This paper presents a comprehensive work incorporating the degradation mechanism of the type I collagen on the nano-scale into a description of the mechanical behavior of the ACL. The developed framework connects a meso-scale molecular dynamics-simulation model to a continuum fibril-reinforced hyper-elastoplastic model. The degradation mechanism was presented by the elimination of the enzymatical crosslinks. This was later well documented as a key element in the collagen's integrity and thereafter expressing a significant role in the yielding tissue level, and serves as an internal control for the integrity of our modeling approach. The proposed engineering frame was validated at two levels, molecular and continuum, by comparing the predictions with reported results in the literature. At the micro-level, the degradation in the enzymatical crosslinks affected the elastic stiffness of the second and third deformation regimes and the collagen failure strain. A higher crosslink density generated a well-connected structure of the collagen fibril. On the macro-scale and by means of the hierarchical model, a limited zone of the elastic and the complete plastic responses were influenced by the degradation of enzymatical crosslinks. In this work, our calculated elastic modulus of the fully crosslinked collagen fibrils at low and high strains levels were about 3.6 GPa and 8.8 GPa, respectively. The moduli decreased significantly with the degradation in the enzymatical crosslinks, reaching 3.2 GPa and 4.8 GPa at small and large strains levels. These predictions are corroborated by experimental measurements of the small and large strain elastic modulus via nanoindentation testing using an atomic-force microscope [57], where the values ranged from 5 to 11.5 GPa. On the computational side, the proposed model in this investigation was able to reproduce the same mechanical behavior of the fully divalent and trivalent crosslinked fibril [36]. Despite the clear agreement in the predicted elasticity of a single TC molecule (Figure 3), a higher estimation of the elastoplastic behavior of the fibrils has been predicted via the 2D meso-scale models of the collagen fibril compared to the current results [21; 42]. The overestimation of the fibril 2D model may be explained by a combination of size effects, entropic effects, and model parameterization errors [58; 59; 60; 61]. The yield strain of the collagen fibril was in the range 0.07-0.38 for different crosslink densities, which is in the same range of experimental and computational investigation [12; 52]. At the same time, our predicted yield strength in all cases was beyond the experimental findings [12], and this was due to the difference in the considered volume and absence of any molecular defect of the collagen fibrils [21]. Our results support the earlier observation of the importance of the crosslinks content in the yielding stress and post-yield energy absorption [52]. As an extreme example, substantial increases of 3.2 and 4.5 times in the fibril strength and yield strain, respectively, were computed between un-crosslinked and fully crosslinked fibrils. This substantial increase may be explained by the mechanism of the interaction between the TC molecules. As the molecules were pulled away from each other in uniaxial tension, the crosslinks, connecting adjacent molecules, prevented the sliding between molecules. The strength of the crosslink bonds was much stronger than the Lennard-Jones pair interaction keeping the pack of molecules together, resulting in increased yield strength and strain. On the aggregate side, the effect of the crosslink degradation was almost negligible in the range of ACL axial strain, varying from 0 to 6% (Figure 5). However, the supported elastic stresses by the ACL decreased significantly with the degradation of the crosslinks, reaching its maximum of 53% from the native (100%) to fully degraded (0%) fibrils at 8.4% axial strain.