title: Lentiviral-based BMP4 in vivo gene transfer strategy increases pull-out tensile strength without an improvement in the osteointegration of the tendon graft in a rat model of biceps tenodesis.
abstract: BACKGROUND
  The present study aimed to develop a rat model of biceps tenodesis and to assess the feasibility of a lentiviral (LV)-based bone morphogenetic protein (BMP) 4 in vivo gene transfer strategy for healing of biceps tenodesis.
  
  
  METHODS
  A rat model of biceps tenodesis was developed with an interference-fit open surgical technique. A LV vector expressing a BMP4 gene or β-galactosidase (β-gal) control gene was applied to the bone tunnel and the tendon graft before its insertion into the bone tunnel. Osteointegration was assessed by histology and pull-out tensile strength was measured by a biomechanical test suitable for small rat biceps tendon grafts.
  
  
  RESULTS
  Neo-chondrogenesis was seen at the tendon-bone interface of LV-BMP4-treated but not control rats. The LV-BMP4-treated rats showed 32% (p < 0.05) more newly-formed trabecular bone at the tendon-bone junction than the LV-β-gal-treated controls after 3 weeks. However, the sites of neo-chondrogenesis and new bone formation in the LV-BMP4-treated tenodesis were highly spotty. Although the LV-BMP4 strategy did not promote bony integration of the tendon graft, it yielded a 29.5 ± 11.8% (p = 0.066) increase in improvement the pull-out strength of rat biceps tendons compared to the LV-β-gal treatment after 5 weeks.
  
  
  CONCLUSIONS
  Although the LV-BMP4 in vivo gene transfer strategy did not enhance osteointegration of the tendon graft, it yielded a marked improvement in the return of the pull-out strength of the tendon graft. This presumably was largely a result of the bone formation effect of BMP4 that traps or anchors the tendon graft onto the bony tunnel.
authors: Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, CA 92357, USA.
authors: Michael J
authors: MJ
authors: Coen
authors: Shin-Tai
authors: ST
authors: Chen
authors: Charles H
authors: CH
authors: Rundle
authors: Jon E
authors: JE
authors: Wergedal
authors: Kin-Hing William
authors: KH
authors: Lau
mesh_terms: D000818:Animals; D001132:Arm / Q000033:anatomy & histology / Q000601:surgery*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics* / Q000378:metabolism; D020219:Chondrogenesis / Q000502:physiology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008422:Materials Testing; D023421:Models, Animal; D016348:Osseointegration / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D019651:Plastic Surgery Procedures / Q000379:methods; D013314:Stress, Mechanical; D013710:Tendons / Q000637:transplantation*; D053656:Tenodesis; D013718:Tensile Strength
chemical_list: D055415:Bone Morphogenetic Protein 4