Facilitated tendon-bone healing by local delivery of recombinant hepatocyte growth factor in rabbits.
OBJECTIVE
This study was performed to evaluate the therapeutic effect of hepatocyte growth factor (HGF) on tendon-bone healing in a rabbit model.


METHODS
In adult rabbits the long digital extensor tendon was detached from the lateral femoral condyle, and the free end of the tendon was inserted into a tunnel drilled into the proximal tibial metaphysis. Cancellous bone obtained during drilling of the tibial hole was soaked in saline solution or solution containing 100-microg/mL human recombinant HGF and then transplanted into the bone tunnel. Junctional healing between the tendon and the bone was evaluated by histologic analysis and uniaxial load-to-failure testing at 2, 4, 6, 8, and 12 weeks after surgery.


RESULTS
In the saline solution-treated control group, Sharpey-like fibers, which connected the tendon graft and the bone tissue, appeared 6 weeks after treatment. At 8 weeks after treatment, maturation of lamellar bone was seen, and at 12 weeks, the adhesion between tendon and bone appeared to be supported by indirect insertion of fibrocartilaginous tissue, wherein the border between the fibrocartilaginous tissue and tendon or bone was significant. In the HGF-treated group, the fibrous tissues were parallel to the load axis, and lamellar bone and Sharpey-like fibers appeared as early as 4 weeks after treatment. At 12 weeks, junctional tissue, characterized by a continuous 4-layer structure of bone, calcified cartilage, fibrocartilage, and tendon, was regenerated by a direct insertion. On biomechanical testing, the HGF-treated group had significantly better biomechanical properties than the control group at 2 and 4 weeks. The histologic improvement caused by HGF treatment was associated with the biomechanical improvement.


CONCLUSIONS
Local administration of recombinant HGF promotes the adhesive healing process at the tendon-bone junction, both histologically and mechanically, after ligament reconstruction in a rabbit model.


CONCLUSIONS
Application of HGF may be considered as a new therapeutic approach to accelerate healing and rehabilitation after ligament reconstruction.
Nakase
Junsuke
J
Department of Orthopaedic Surgery, School of Medicine, Kanazawa University, Kanazawa, Japan. nakase1007@yahoo.co.jp
Kitaoka
Katsuhiko
K
Matsumoto
Kunio
K
Tomita
Katsuro
K
D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery*; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D002113:Calcification, Physiologic / Q000187:drug effects; D019902:Chondrocytes / Q000648:ultrastructure; D004341:Drug Evaluation; D051445:Fibrocartilage / Q000648:ultrastructure; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D019859:Proto-Oncogene Proteins c-met / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D019651:Plastic Surgery Procedures; D012038:Regeneration / Q000187:drug effects; D013709:Tendon Transfer; D013710:Tendons / Q000601:surgery* / Q000648:ultrastructure; D013718:Tensile Strength; D013977:Tibia / Q000601:surgery*; D016474:Weight-Bearing; D014945:Wound Healing / Q000187:drug effects*
D010446:Peptide Fragments; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met