Studies in flexor tendon wound healing:: Neutralizing antibody to TGF-β1 increases postoperative range of motion

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 harle implicated transforming growth factor beta-1 (TGF-beta 1) in both intrinsic and extrinsic mechanisms of repair. TGF-beta 1 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-beta 1 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 mu g neutralizing antibody to TGF-beta 1; (3) 50 mu g each of neutralizing antibody to TGF-beta 1 and to TGF-beta 2. Eight rabbit 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 allo iv 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 +/- 0 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-beta 1, flexion range of motion increased to 32 +/- 9 degrees (n = 7; p = 0.002). Interestingly, a combination of neutralizing antibody to TGF-beta 1 and that to TGF-beta 2 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-beta 1 improves flexor tendon excursion; and (3) simultaneous infiltration of neutralizing antibody to TGF-beta 2 nullifies this effect. Because TGF-beta 1 is thought to contribute to the pathogenesis of excessive scar formation, the findings presented here suggest that intraoperative biochemical modulation of TGF-beta 1 levels limits flexor tendon adhesion formation.