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Fig 1.

Anatomic dissection of the Achilles (A) and plantaris tendons in rabbits (B). (A) Posterior view. (B) Lateral view. The plantaris tendon is located in a superficial and dorsal position in relation to the Achilles tendon.

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Fig 2.

Tendon injection procedure.

Injection performed under direct visualization, in the central region of the substance of the Achilles tendon, using 27 gauge needle coupled in a 100 microliters syringe.

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Fig 3.

Distribution of the study groups.

Flowchart for groups distributions, timing of injections and euthanasias.

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Fig 4.

Histological Bonar score grading system.

Five different characteristics evaluated, each one graded from zero to three: Line 1: cell morphology (200x magnification, H&E and safranin); Line 2: cellularity (100x magnification, H&E); Line 3: vascularization (400x magnification, H&E); Line 4: accumulation of ground substance (100x magnification, Alcian blue); Line 5: collagen fibers arrangement (polarized light, 100x magnification, picrosirius).

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Fig 5.

Biomechanical analysis.

Specimen (A) attached to the test machine by a cylindrical (B) and a cryogenic clamp (C).

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Fig 6.

Histological results after 16 weeks.

(A) Hematoxylin-Eosin, 40x. Control Group: cell morphology slightly altered, well delimited collagen bundles, minimal increase in cellularity, no changes in vascularization or ground substance. (B) HD Group: increased cellularity, altered cellular morphology with greater roundness of the cellular nuclei, loss of the wavy pattern of collagen bundles and areas of neovascularization (black arrows). (C) LD Group: Areas of increased, decreased and acellularity, destruction of collagen bundle architecture, increased number vascular clusters (black arrows) loss of collagen bundle architecture (D) LD Group: diffuse increase of the ground substance, altered cellular morphology, rounding of cell nuclei with halo formation, compatible with chondroid metaplasia (white arrows).

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Table 1.

Histological Bonar score: Mean values, standard deviation, Minimum, Median and Maximum values by Group at different euthanasia time-points.

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Table 2.

Two-Way ANOVA analysis for histological Bonar score.

Degrees of Freedom, Sum of Squares, Mean Square, F-Value and P-values. Significant influences observed for all variables: Group, Time-point (Weeks) and interaction between Group and Time-point.

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Table 3.

Biomechanical parameters at 10 weeks: Mean value and standard deviation for specimens in the Low-Dose (LD) and High-Dose (HD) Groups.

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Table 4.

Biomechanical parameters at 12 weeks: Mean value and standard deviation for specimens in the Low-Dose (LD) and High-Dose (HD) Groups.

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Table 5.

Biomechanical parameters at 16 weeks: Mean value and standard deviation (SD) for specimens in the Low-Dose (LD), High-Dose (HD) and control Groups.

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