Direct lentiviral-cyclooxygenase 2 application to the tendon-bone interface promotes osteointegration and enhances return of the pull-out tensile strength of the tendon graft in a rat model of biceps tenodesis.
This study sought to determine if direct application of the lentiviral (LV)-cyclooxygenase 2 (COX2) vector to the tendon-bone interface would promote osteointegration of the tendon graft in a rat model of biceps tenodesis. The LV-COX2 gene transfer strategy was chosen for investigation because a similar COX2 gene transfer strategy promoted bony bridging of the fracture gap during bone repair, which involves similar histologic transitions that occur in osteointegration. Briefly, a 1.14-mm diameter tunnel was drilled in the mid-groove of the humerus of adult Fischer 344 rats. The LV-COX2 or βgal control vector was applied directly into the bone tunnel and onto the end of the tendon graft, which was then pulled into the bone tunnel. A poly-L-lactide pin was press-fitted into the tunnel as interference fixation. Animals were sacrificed at 3, 5, or 8 weeks for histology analysis of osteointegration. The LV-COX2 gene transfer strategy enhanced neo-chondrogenesis at the tendon-bone interface but with only marginal effect on de novo bone formation. The tendon-bone interface of the LV-COX2-treated tenodesis showed the well-defined tendon-to-fibrocartilage-to-bone histologic transitions that are indicative of osteointegration of the tendon graft. The LV-COX2 in vivo gene transfer strategy also significantly enhanced angiogenesis at the tendon-bone interface. To determine if the increased osteointegration was translated into an improved pull-out mechanical strength property, the pull-out tensile strength of the LV-COX2-treated tendon grafts was determined with a pull-out mechanical testing assay. The LV-COX2 strategy yielded a significant improvement in the return of the pull-out strength of the tendon graft after 8 weeks. In conclusion, the COX2-based in vivo gene transfer strategy enhanced angiogenesis, osteointegration and improved return of the pull-out strength of the tendon graft. Thus, this strategy has great potential to be developed into an effective therapy to promote tendon-to-bone healing after tenodesis or related surgeries.
Musculoskeletal Disease Center, J. L. Pettis Memorial VA Medical Center, Loma Linda, California, United States of America; Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California, United State of America.
Charles H
CH
Rundle
Musculoskeletal Disease Center, J. L. Pettis Memorial VA Medical Center, Loma Linda, California, United States of America; Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California, United State of America; Department of Biochemistry, Loma Linda University School of Medicine, Loma Linda, California, United State of America.
Shin-Tai
ST
Chen
Musculoskeletal Disease Center, J. L. Pettis Memorial VA Medical Center, Loma Linda, California, United States of America; Department of Orthopedic Surgery, Loma Linda University School of Medicine, Loma Linda, California, United State of America.
Michael J
MJ
Coen
Musculoskeletal Disease Center, J. L. Pettis Memorial VA Medical Center, Loma Linda, California, United States of America; Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California, United State of America; Department of Biochemistry, Loma Linda University School of Medicine, Loma Linda, California, United State of America.
Jon E
JE
Wergedal
Musculoskeletal Disease Center, J. L. Pettis Memorial VA Medical Center, Loma Linda, California, United States of America.
Virginia
V
Stiffel
Musculoskeletal Disease Center, J. L. Pettis Memorial VA Medical Center, Loma Linda, California, United States of America; Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California, United State of America; Department of Biochemistry, Loma Linda University School of Medicine, Loma Linda, California, United State of America.
Kin-Hing William
KH
Lau
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism / Q000502:physiology* / Q000601:surgery; D020219:Chondrogenesis; D051546:Cyclooxygenase 2 / Q000235:genetics*; D018014:Gene Transfer Techniques; D016086:Lentivirus / Q000235:genetics*; D016348:Osseointegration; D010012:Osteogenesis; D051381:Rats; D013710:Tendons / Q000601:surgery / Q000637:transplantation*; D053656:Tenodesis / Q000379:methods*; D013718:Tensile Strength; D034941:Upper Extremity / Q000601:surgery*; D014945:Wound Healing
D051546:Cyclooxygenase 2