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The postoperative outcome of hand flexor tendon repair remains limited by tendon adhesions that prevent normal range of motion. Recent studies using in situ hybridization techniques have implicated transforming growth factor beta-1 (TGF-beta1) in both intrinsic and extrinsic mechanisms of repair. TGF-beta1 is a growth factor that plays multiple roles in wound healing and has also been implicated in the pathogenesis of excessive scar formation. The purpose of this study was to examine the effect of neutralizing antibody to TGF-beta1 in a rabbit zone II flexor tendon wound-healing model. Twenty-two adult New Zealand White rabbits underwent complete transection of the middle digit flexor digitorum profundus tendon in zone II. The tendons were immediately repaired and received intraoperative infiltration of one of the following substances: (1) control phosphate-buffered saline; (2) 50 microg neutralizing antibody to TGF-beta1; (3) 50 microg each of neutralizing antibody to TGF-beta1 and to TGF-beta2. Eight rabbits that had not been operated on underwent analysis for determination of normal flexion range of motion at their proximal and distal interphalangeal joints, using a 1.2-N axial load applied to the flexor digitorum profundus tendon. All rabbits that had been operated on were placed in casts for 8 weeks to allow maximal tendon adhesion and were then killed to determine their flexion range of motion. Statistical analysis was performed using the Student's unpaired t test. When a 1.2-N load was used on rabbit forepaws that had not been operated on, normal combined flexion range of motion at the proximal and distal interphalangeal joints was 93+/-6 degrees. Previous immobilization in casts did not reduce the range of motion in these forepaws (93+/-4 degrees). In the experimental groups, complete transection and repair of the flexor digitorum profundus tendon with infiltration of control phosphate-buffered saline solution resulted in significantly decreased range of motion between the proximal and distal phalanges [15+/-6 degrees (n = 8)]. However, in the tendon repairs infiltrated with neutralizing antibody to TGF-beta1, flexion range of motion increased to 32+/-9 degrees (n = 7; p = 0.002). Interestingly, a combination of neutralizing antibody to TGF-beta1 and that to TGF-beta2 did not improve postoperative range of motion [18+/-4 degrees (n = 7; p = 0.234)]. These data demonstrate that (1) the rabbit flexor tendon repair model is useful for quantifying tendon scar formation on the basis of degrees of flexion between proximal and distal phalanges; (2) intraoperative infiltration of neutralizing antibody to TGF-beta1 improves flexor tendon excursion; and (3) simultaneous infiltration of neutralizing antibody to TGF-beta2 nullifies this effect. Because TGF-beta1 is thought to contribute to the pathogenesis of excessive scar formation, the findings presented here suggest that intraoperative biochemical modulation of TGF-beta1 levels limits flexor tendon adhesion formation.

Future studies need to evaluate the most promising monitoring techniques further with a focus on assessing clinically relevant outcomes, such as the flap salvage rate and the false-positive rate, and not simple clinical series reporting patient and physician satisfaction.

This study evaluated the effect of exogenous vascular endothelial growth factor (VEGF) on tendon healing and regulation of other growth factors in a rat Achilles tendon model. Fifty Sprague-Dawley rats were used. In the experimental group, the left Achilles tendon was transected and repaired with the modified Kessler suture technique, and the right Achilles tendon was transected and repaired with resection of plantaris tendon. VEGF, 100 mul (50 mug/ml), was injected into each tendon at the repair site. The same surgical procedures were performed in the control group, with the same volume of saline injected into the repair sites. At intervals of 1, 2, and 4 weeks, the animals were killed and the tendons were harvested and evaluated for tensile strength (1, 2, and 4 weeks) and gene expression (postoperative day 4). At 1 week postoperatively, when plantaris tendon was preserved, the tensile strength of the repaired tendons with VEGF treatment (3.63 +/- 0.62 MPa) was significantly higher than the tensile strength of the repaired tendons with saline treatment (2.20 +/- 0.36 MPa). There was no difference in tensile strength between the two groups without the plantaris tendon support. At 2 weeks postoperatively, the tensile strength was 11.34 +/- 3.89 MPa in the group with VEGF treatment and plantaris tendon preservation, which was significantly higher than the tensile strength in the other groups. There was no significant difference in tensile strength among the groups at 4 weeks postoperatively. The gene expression showed that transforming growth factor-beta in the VEGF-treated tendon was up-regulated in the early stage of tendon healing, whereas expression of platelet-derived growth factor, basic fibroblast growth factor, and insulin-like growth factor-1 was not significantly different among the groups. In conclusion, administration of exogenous VEGF can significantly improve tensile strength early in the course of the rat Achilles tendon healing and was associated with increased expression of transforming growth factor-beta.