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Acceleration of tendon healing using US guided intratendinous injection of bevacizumab: First pre-clinical study on a murine model
Authors:Benjamin Dallaudiè  re,Marta Lempicki,Lionel Pesquer,Liliane Louedec,Pierre Marie Preux,Philippe Meyer,Agathe Hess,Marie Hè    ne Moreau Durieux,Vincent Hummel,Ahmed Larbi,Lydia Deschamps,Yohan Benayoun,Clement Journe,Anne Perozziello,Elisabeth Schouman-Claeys,Jean Baptiste Michel,Jean Michel Serfaty
Affiliation:1. Service de Radiologie, Hôpital universitaire Bichat, Paris, France;2. Inserm U698, Hôpital universitaire Bichat, Paris, France;3. Université de Médecine Paris Diderot, France;4. Centre d’Imagerie Ostéo Articulaire, Clinique du Sport de Bordeaux-Mérignac, France;5. Laboratoire de Biostatistiques, Faculté de médecine, Limoges, France;6. Service d’ Anatomopathologie, Hôpital universitaire Bichat, Paris, France;g Institut Claude Bernard, Centre d’imagerie fonctionnelle, Bichat, Paris, France;h Unité de Recherche Clinique, Paris nord, France
Abstract:

Purpose

Tendinopathy shows early disorganized collagen fibers with neo-angiogenesis on histology. Peri-tendinous injection of corticosteroid is the commonly accepted strategy despite the abscence of inflammation in tendinosis. The aim of our study was to assess the potential of intratendinous injection of an anti-angiogenic drug (bevacizumab, AA) to treat tendinopathy in a murine model of patellar and Achilles tendinopathy, and to evaluate its local toxicity.

Materials and method

Forty rats (160 patellar and Achilles tendons) were used for this study. We induced tendinosis (T+) in 80 tendons by injecting under ultrasonography (US) guidance Collagenase 1® (day 0 = D0, patellar = 40 and Achilles = 40). Clinical examination and tendon US were performed at D3, immediately followed by either AA (AAT+, n = 40) or physiological serum (PST+, n = 40, control) US-guided intratendinous injection. Follow-up at D6 and D13 using clinical, US and histology, and comparison between the 2 groups were performed. To study AA toxicity we compared the 80 remaining normal tendons (T−) after injecting AA in 40 (AAT−).

Results

All AAT+ showed a better joint mobilization compared to PST+ at D6 (p = 0.004) with thinner US tendon diameters (p < 0.004), and less disorganized collagen fibers and neovessels on histology (p < 0.05). There was no difference at D13 regarding clinical status, US tendon diameter and histology (p > 0.05). Comparison between AAT− and T− showed no AA toxicity on tendon (p = 0.18).

Conclusion

Our study suggests that high dose mono-injection of AA in tendinosis, early after the beginning of the disease, accelerates tendon's healing, with no local toxicity.
Keywords:Tendon   Anti-angiogenic   Tendinosis   Rat   US
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