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Spatiotemporal and microstructural characterization of heterotopic ossification in healing rat Achilles tendons

Journal

FASEB JOURNAL
Volume 37, Issue 6, Pages -

Publisher

WILEY
DOI: 10.1096/fj.202201018RRR

Keywords

endochondral; mineralization template; pathologic calcification; synchrotron imaging

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Achilles tendon rupture is a common medical condition that can result in functional loss. The healing process is slow and can be affected by heterotopic ossification (HO), which is the pathological formation of bone tissue instead of tendon tissue. This study used advanced imaging techniques to examine the temporal and spatial progression of HO during Achilles tendon healing in a rat model. The results revealed that HO deposition begins as early as one week after injury in the distal stump and mostly grows on preexisting HO deposits. These deposits become larger and calcified, occupying up to 10% of the tendon volume. The study provides valuable insights into the ossification process in healing tendons.
Achilles tendon rupture is a common debilitating medical condition. The healing process is slow and can be affected by heterotopic ossification (HO), which occurs when pathologic bone-like tissue is deposited instead of the soft collagenous tendon tissue. Little is known about the temporal and spatial progression of HO during Achilles tendon healing. In this study we characterize HO deposition, microstructure, and location at different stages of healing in a rat model. We use phase contrast-enhanced synchrotron microtomography, a state-of-the-art technique that allows 3D imaging at high-resolution of soft biological tissues without invasive or time-consuming sample preparation. The results increase our understanding of HO deposition, from the early inflammatory phase of tendon healing, by showing that the deposition is initiated as early as one week after injury in the distal stump and mostly growing on preinjury HO deposits. Later, more deposits form first in the stumps and then all over the tendon callus, merging into large, calcified structures, which occupy up to 10% of the tendon volume. The HOs were characterized by a looser connective trabecular-like structure and a proteoglycan-rich matrix containing chondrocyte-like cells with lacunae. The study shows the potential of 3D imaging at high-resolution by phase-contrast tomography to better understand ossification in healing tendons.

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