Abstract
Tendinopathy is a big burden in clinics and it represents 45% of musculoskeletal lesions. Despite the relevant social impact, both pathogenesis and development of the tendinopathy are still under-investigated, thus limiting the therapeutic advancement in this field. The purpose of this study was to evaluate the dose-dependent and time-related tissue-level changes occurring in a collagenase-induced tendinopathy in rat Achilles tendons, in order to establish a standardized model for future pre-clinical studies. With this purpose, 40 Sprague Dawley rats were randomly divided into two groups, treated by injecting collagenase type I within the Achilles tendon at 1 mg/mL (low dose) or 3 mg/mL (high dose). Tendon explants were histologically evaluated at 3, 7, 15, 30 and 45 days. Our results revealed that both the collagenase doses induced a disorganization of collagen fibers and increased the number of rounded resident cells. In particular, the high dose treatment determined a greater neovascularization and fatty degeneration with respect to the lower dose. These changes were found to be time-dependent and to resemble the features of human tendinopathy. Indeed, in our series, the acute phase occurred from day 3 to day 15, and then progressed towards the proliferative phase from day 30 to day 45 displaying a degenerative appearance associated with a very precocious and mild remodeling process. The model represents a good balance between similarity with histological features of human tendinopathy and feasibility, in terms of tendon size to create lesions and costs when compared to other animal models. Moreover, this model could contribute to improve the knowledge in this field, and it could be useful to properly design further pre-clinical studies to test innovative treatments for tendinopathy.
Highlights
The sham control (S-CTRL) tendons showed a uniform appearance of compact, well-aligned collagen fibers with a normal presence of spindle-shaped tenocytes disposed parallel to the fiber pattern, and, as expected, no degenerative events were observed during the whole study period (Fig 2)
Tendinopathy is an umbrella term that refers to tendon injury with unknown etiology [24]
Tendinopathy has been defined as tendinitis when a non-rupture tendon injury is associated with a very precocious inflammatory process [25]
Summary
Tendinopathy is a big burden in clinics and it represents 45% of musculoskeletal lesions [1]. Athletes and middle-aged people are frequently affected by tendinopathy of Achilles, patellar and supraspinatus tendons. The poor healing capability of damaged tendons is related to their scarce blood supply and the compromised metabolic activity of resident cells [3] that determine an impaired tissue homeostasis [4]. The histopathological appearance of injured tendons shows collagen degeneration and fiber disorganization, increased vascularization and increased presence of resident cells, tissue metaplasia, and occasionally formation of fatty and bony deposits [5, 6]. Despite its clinical significance, the pathogenesis and development of the tendinopathy are still underinvestigated, limiting the therapeutic progress in this field. The current conservative treatments are still mainly symptomatic, whereas surgical approaches have a poor success rate and require a long recovery time [7]
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