The effects of exogenous basic fibroblast growth factor on intrasynovial flexor tendon healing in a canine model.

Background: Studies have demonstrated thatflexor tendon repair strength fails to increase in thefirstthree weeks following suturing ofthetendon,afindingthatcorrelatescloselywiththetimingofmanyclinical failures.Theapplicationofgrowthfactorsholdspromisefor improving the tendon-repair response and obviating failure in the initial three weeks. Methods: The effects of basic fibroblast growth factor on flexor tendon healing were evaluated with use of a canine model. Operative repair followed by the sustained delivery of basic fibroblast growth factor, at two different doses, was compared with operative repair alone. Histological, biochemical, and biomechanical methods were used to evaluate the tendons twenty-one days after repair. Results: Vascularity, cellularity, and adhesion formation were increased in the tendons that received basic fibroblast growth factor as comparedwiththe tendons that received operative repair alone. DNA concentration was increased in the tendons that received 1000 ng of basicfibroblast growthfactor(meanand standarddeviation,5.7±0.7 mg/mg)ascompared with the tendonsthat received 500 ngofbasic fibroblast growth factor (3.8 ± 0.7 mg/mg) and the matched control tendons that received operative repair alone (4.5 ± 0.9 mg/mg). Tendonsthatweretreatedwithbasicfibroblastgrowthfactorhadalowerratiooftype-Icollagentotype-IIIcollagen,indicatingincreasedscar formation compared with that seen in tendons that received operative repair alone (3.0 ± 1.6 in the group that received 500-ng basic fibroblast growth factor compared with 4.3 ± 1.0 in the paired control group that received operative repair alone, and 3.4± 0.6 in the group that received 1000-ng basic fibroblast growth factor compared with 4.5 ± 1.9 in the paired control group that received operative repair alone).Consistentwith the increasesinadhesion formation thatwereseen intendonstreated with basicfibroblastgrowthfactor,the range of motionwasreducedinthegroup thatreceivedthehigherdose of basicfibroblast growthfactorthanitwasinthepairedcontrolgroupthat received operative repair alone (16.6� ± 9.4� in the group that received 500 ng basic fibroblast growth factor, 13.4� ± 6.1� in the paired controlgroup that received operativerepairalone,and29.2� ± 5.8� inthe normalgroup [i.e.,the groupof corresponding,uninjured tendons from the contralateral forelimb]; and 15.0� ± 3.8� in the group that received 1000 ng basic fibroblast growth factor, 19.3� ± 5.5� in the paired control group that received operative repair alone, and 29.0� ± 8.8� in the normal group). There were no significant differences in tendon excursion or tensile mechanical properties between the groups that were treated with basic fibroblast growth factor and the groups that received operative repair alone. Conclusions: Although basic fibroblast growth factor accelerated the cell-proliferation phase of tendon healing, it also promoted neovascularization and inflammation in the earliest stages following the suturing ofthe tendon. Despite a substantial biologic response, the administration of basic fibroblast growth factor failed to produce improvements in either the mechanical or functional properties of the repair. Rather, increased cellular activity resulted in peritendinous scar formation and diminished range of motion. Clinical Relevance: Despite success in stimulating cellular proliferation and matrix synthesis in flexor tendons through the application of a growth factor in a clinically relevant animal model, no significant improvements were noted in either functional or structural properties. Therefore, as applied in this model, basic fibroblast growth factor is not recommended for intrasynovial flexor tendon repair.