Facilitated Tendon-Bone Healing by Local Delivery of Recombinant Hepatocyte Growth Factor in Rabbits

SLR - April 2010 - Cody Fox

Reference: 
Nakase J, Kitoaka K, Matsumoto K, Tomita K (2010) Arthroscopy: The Journal of Arthroscopy and Related Surgery, Vol 26, No 1 pp84-90

Scientific Literature Reviews

Reviewed by:  Cody Fox, DPM
Residency Program: Detroit Medical Center

Podiatric Relevance:
A possible new therapeutic technique to facilitate healing in tendon and ligament reconstruction is present.

Methods:
The authors studied the use of recombinant human hepatocyte growth factor (HGF) in tendon-bone healing.  They took 50 adult rabbits, 25 rabbits treated with HGF and 25 treated with saline.  They detached the extensor tendon of the femur distally from the lateral femoral condyle. Using a 2.5mm drill bit, they made a drill hole in the proximal tibial metaphysis at a 90 degree angle to the shaft.  The free end of the tendon was sutured with 3-0 vicryl and inserted into the drill hole and fixated using a stainless suture button.  Cancellous bone from the tibial drilling was then soaked for 15 minutes in either saline or a solution containing HGF and transplanted into the bone tunnel.  One hundred microliters of  saline or HGF was then injected into the bone tunnel.  Left limbs were treated with saline and right with HGF.  The rabbits were allowed to exercise post-operatively.   Adhesion of the tendon to bone was then analyzed histologically for 12 weeks post-operatively. 

Results: 
After two weeks, the saline-treated group demonstrated inflammatory cells and fibrovascular infiltration at the bone-tendon interface with evidence of sparse collagen with no directionality.  There was evidence of woven bone in the tunnel.  The HGF group demonstrated organized collagen and more woven bone than the saline group.  At four weeks, the saline group showed directionally arranged collagen fibers and increased maturity woven bone.  In the HGF group, the fibrous tissue was parallel to the load axis and there was evidence of lamellar bone and sharpey-like fibers.  At six weeks, the saline group showed maturing of woven bone to lamellar bone and few sharpey-like fibers.  In the HGF group, the lamellar bone matured and sharpey-like fibers were organized into bundles.  Week 8, the saline group lamellar bone matured and bundle-shaped sharpey-like fibers emerged.  In the HGF group sharpey-like fibers were replaced by a fibrocartilaginous tissue insertion between tendon and bone.  At week 12, fibrocartilaginous tissue appeared in the saline group, and in the HGF group, the adhesion between bone and tendon appeared almost completed

Conclusions:
Administration of the recombinant HGF appears to facilitate and expedite healing and the adhesion of the tendon-bone interface in the rabbit model.