Biomedical Engineering Reference
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Fig. 11.8 Muscle paralysis dramatically impaired the development of the supraspinatus tendon-to-
bone insertion in mice. ( Top ) A mature, compositionally graded insertion (“i”) is seen by 56 days
postnatally in normal mice (scale bar ¼ 200
m). In contrast, the enthesis in paralyzed shoulders
appears disorganized, without a graded fibrocartilaginous transition between the supraspinatus
tendon (“s”) and the humeral head bone (“h”). ( Bottom ) Maximum stress and modulus were
significantly lower in the paralyzed group compared to the normal and saline groups
m
and morphological changes. For example, the humeral head appeared flattened,
similar to observations in children with neonatal brachial plexus palsy. This
demonstrated that mechanical loading is critical for mineralization at the enthesis.
The lower mineral density observed in micro-computed tomography measurements
in the unloaded groups can at least in part be attributed to an increase in osteoclast
activity [ 115 ]. When osteoclast activity was blocked using a bisphosphonate drug,
there was a partial recovery of some bone mineralization measures [ 119 ]. Bone
volume was significantly recovered in a dose-dependent manner.
Removal of muscle loading also affected the development of a fibrocartilaginous
transition at the insertion (Fig. 11.8 ). Based on histological analysis, little to no
fibrocartilage was observed in the insertion after 8 weeks of paralysis [ 115 ].
Collagen fiber alignment, investigated using quantitative polarized light micros-
copy, indicated fibers were more disorganized in unloaded shoulders compared to
saline controls. Impaired mineralization, disordered fiber alignment, and a loss of
fibrocartilage transitional tissue in the insertions likely contribute to the overall
inferior mechanical properties of unloaded tendon insertions. Structural mechanical
properties (e.g., maximum force, stiffness) and material mechanical properties
(e.g., maximum stress, modulus) were decreased after 4 and 8 weeks of botulinum
toxin injections (Fig. 11.8 ).
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