Studies in flexor tendon wound healing: Neutralizing antibody to TGF-beta 1 increases postoperative range of motion

The postoperative outcome of hand flexor tendon repair remains limited by t endon adhesions that prevent normal range of motion. Recent studies using i n 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 an d has also been implicated in the pathogenesis of excessive scar formation. The purpose of this study was to examine the effect of neutralizing antibo dy to TGF-beta 1 in a rabbit zone II flexor tendon wound-healing model. Twenty-two adult New Zealand White rabbits underwent complete transection o f the middle digit flexor digitorum profundus tendon in zone II. The tendon s 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 o perated on underwent analysis for determination of normal flexion range of motion at their proximal and distal interphalangeal joints, using a 1.2-N a xial load applied to the flexor digitorum profundus tendon. All rabbits tha t 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 mo tion. Statistical analysis was performed using the Student's unpaired t tes t. 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 interp halangeal joints was 93 +/- 0 degrees. Previous immobilization in casts did not reduce the range of motion in these forepaws (93 +/- 4 degrees). In th e experimental groups, complete transection and repair of the flexor digito rum profundus tendon with infiltration of control phosphate-buffered saline solution resulted in significantly decreased range of motion between the p roximal and distal phalanges [15 +/- 6 degrees (n = 8)]. However, in the te ndon repairs infiltrated with neutralizing antibody to TGF-beta 1, flexion range of motion increased to 32 +/- 9 degrees (n = 7; p = 0.002). Interesti ngly, 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 us eful for quantifying tendon scar formation on the basis of degrees of flexi on between proximal and distal phalanges; (2) intraoperative infiltration o f neutralizing antibody to TGF-beta 1 improves flexor tendon excursion; and (3) simultaneous infiltration of neutralizing antibody to TGF-beta 2 nulli fies this effect. Because TGF-beta 1 is thought to contribute to the pathog enesis of excessive scar formation, the findings presented here suggest tha t intraoperative biochemical modulation of TGF-beta 1 levels limits flexor tendon adhesion formation.