The mechanical properties of tendon autografts used in reconstruction of the anterior cruciate ligament (ACL) are reduced after surgery. Previous studies showed that growth factors such as transforming growth factor-(31 (TGF-(31) and epidermal growth factor (EGF) can stimulate fibroblast proliferation and increase collagen and noncollagenous protein synthesis by these cells. These factors might be useful, therefore, in preventing graft deterioration after transplantation or accelerating mechanical restoration of the deteriorated graft. The purpose of our study, therefore, was to clarify the effects of TGF-(31 and EGF on biomechanical properties using an in situ freeze-thaw ACL model in the rabbit. A total of 142 rabbits underwent the freeze-thaw treatment in the right ACL and were then divided into four groups. Group I served as a freeze-thaw, but otherwise untreated control. In Group 11, a delivery vehicle (fibrin sealant) alone was applied. In Group 111, 4-ng TGF-PI and 100-ng EGF mixed with the vehicle were applied, In Group IV, higher doses (2-pg TGF-(31 and 50-pg EGF) of growth factors were mixed with the vehicle. The groups were compared at 6 and 12 weeks on the basis of mechanical properties, water content, and histological and ultrastructural observations. The crosssectional area of Group 111 (average, 7.1 mm') was significantly less than that of Groups I, TI, and IV (9.0, 8.2, and 9.4 mm2, respectively) at 12 weeks. The tensile strength of Group I11 (62.2 MPa) was significantly greater than that of Groups I, 11, and IV (35.6, 43.7, and 36.9 MPa, respectively) at 12 weeks, while the water content of Group 111 (70.7'%,) was significantly lower than that of Group I (75.2%). No other significant differences occurred among Groups I, 11, and IV. A unirnodal distribution of collagen fibril diameters was noted in Groups I and 11, while a bimodal pattern was found in Group 111. This study demonstrated that low-dose application of TGF-P1 and EGF significantly inhibited not only the increased water content and cross-sectional area, but also the decreased tensile strength caused by the freeze-thaw treatment, while a high dose of TGF-PI and EGF does not have the same beneficial effects.
