Platelet-rich plasma (PRP) and broad-spectrum matrix metalloproteinase inhibitors (MMPIs) have been used as therapeutic options for tendinopathy. However, mixed results have been reported regarding their efficacy. We posited that the combination of these two treatment strategies would be more beneficial for healing tendons than each treatment alone. Rat tail tendons were harvested and cultured without mechanical stress for 0, 4, or 10 days. Single and combination treatment with PRP and MMPIs with either broad- or narrow-spectrum (MMP-13 selective), was administered to 4-day stress-deprived (SD) tendons, an ex vivo model for moderate tendinopathy. This treatment was applied to the damaged tendons over 6 days. At the end of their culture time, the tendons were subjected to traction testing and pathohistology, immunohistochemistry, and viability assays. The results showed better histological features for the PRP + narrow-spectrum MMPI group compared with all individual treatment modalities. Moreover, higher fiber density, more elongated nucleus shape, smaller space between fibers, and a trend toward higher mechanical strength were noted for PRP + narrow-spectrum MMPI group compared with 10-day SD tendons. This study shows that the combination of PRP + narrow-spectrum MMPI is a potentially effective treatment approach for tendinopathy. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1838-1847, 2019.
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