title: Acceleration of tendon healing using US guided intratendinous injection of bevacizumab: first pre-clinical study on a murine model.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service de Radiologie, Hôpital universitaire Bichat, Paris, France; Inserm U698, Hôpital universitaire Bichat, Paris, France; Université de Médecine Paris Diderot, France. Electronic address: bendallau64@hotmail.fr.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dallaudière
authors.forename: Marta
authors.initials: M
authors.lastname: Lempicki
authors.forename: Lionel
authors.initials: L
authors.lastname: Pesquer
authors.forename: Liliane
authors.initials: L
authors.lastname: Louedec
authors.forename: Pierre Marie
authors.initials: PM
authors.lastname: Preux
authors.forename: Philippe
authors.initials: P
authors.lastname: Meyer
authors.forename: Agathe
authors.initials: A
authors.lastname: Hess
authors.forename: Marie Hèlène Moreau
authors.initials: MH
authors.lastname: Durieux
authors.forename: Vincent
authors.initials: V
authors.lastname: Hummel
authors.forename: Ahmed
authors.initials: A
authors.lastname: Larbi
authors.forename: Lydia
authors.initials: L
authors.lastname: Deschamps
authors.forename: Yohan
authors.initials: Y
authors.lastname: Benayoun
authors.forename: Clement
authors.initials: C
authors.lastname: Journe
authors.forename: Anne
authors.initials: A
authors.lastname: Perozziello
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schouman-Claeys
authors.forename: Jean Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Serfaty
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000068258:Bevacizumab; D017364:Collagenases; D004195:Disease Models, Animal; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D052256:Tendinopathy / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional / Q000379:methods*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D017364:Collagenases
keywords: Anti-angiogenic; Rat; Tendinosis; Tendon; US