PXL01 in sodium hyaluronate for improvement of hand recovery after flexor tendon repair surgery: randomized controlled trial.

BACKGROUND: Postoperative adhesions constitute a substantial clinical problem in hand surgery. Fexor tendon injury and repair result in adhesion formation around the tendon, which restricts the gliding function of the tendon, leading to decreased digit mobility and impaired hand recovery. This study evaluated the efficacy and safety of the peptide PXL01 in preventing adhesions, and correspondingly improving hand function, in flexor tendon repair surgery. METHODS: This prospective, randomised, double-blind trial included 138 patients admitted for flexor tendon repair surgery. PXL01 in carrier sodium hyaluronate or placebo was administered around the repaired tendon. Efficacy was assessed by total active motion of the injured finger, tip-to-crease distance, sensory function, tenolysis rate and grip strength, and safety parameters were followed, for 12 months post-surgery. RESULTS: The most pronounced difference between the treatment groups was observed at 6 months post-surgery. At this timepoint, the total active motion of the distal finger joint was improved in the PXL01 group (60 vs. 41 degrees for PXL01 vs. placebo group, p = 0.016 in PPAS). The proportion of patients with excellent/good digit mobility was higher in the PXL01 group (61% vs. 38%, p = 0.0499 in PPAS). Consistently, the PXL01 group presented improved tip-to-crease distance (5.0 vs. 15.5 mm for PXL01 vs. placebo group, p = 0.048 in PPAS). Sensory evaluation showed that more patients in the PXL01 group felt the thinnest monofilaments (FAS: 74% vs. 35%, p = 0.021; PPAS: 76% vs. 35%, p = 0.016). At 12 months post-surgery, more patients in the placebo group were considered to benefit from tenolysis (30% vs. 12%, p = 0.086 in PPAS). The treatment was safe, well tolerated, and did not increase the rate of tendon rupture. CONCLUSIONS: Treatment with PXL01 in sodium hyaluronate improves hand recovery after flexor tendon repair surgery. Further clinical trials are warranted to determine the most efficient dose and health economic benefits. TRIAL REGISTRATION: ClinicalTrials.gov NCT01022242; EU Clinical Trials 2009-012703-25.

Neuropeptide, mast cell, and myofibroblast expression after rabbit deep flexor tendon repair.

PURPOSE: Increased numbers of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers have been found in a number of fibrotic processes in connective tissues. The purpose of the present study was to investigate the occurrence of factors implicated in a hypothesized profibrotic neuropeptide-mast cell-myofibroblast pathway in deep flexor tendon healing. METHODS: In a rabbit model of flexor tendon injury, with repair of the sharply transected deep flexor tendon using a modified Kessler and a running circumferential peripheral suture, segments of flexor tendons and sheaths were analyzed. The time points chosen-3, 6, 21, and 42 days after tendon repair-represent different stages in tendon healing. The messenger RNA levels of transforming growth factor-ß1 and α-smooth muscle actin were measured with conventional reverse transcription-polymerase chain reaction, and the numbers of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers were determined with immunohistochemistry. RESULTS: The messenger RNA levels for transforming growth factor-ß1 and the myofibroblast marker α-smooth muscle actin were significantly increased in deep flexor tendons after injury and repair, at all studied time points, but remained unchanged or even down-regulated in the sheaths. Myofibroblasts, mast cells, and neuropeptide-containing nerve fibers all increased significantly in the healing tendons, exhibiting similar patterns of change in percentages of total cell number over time, reaching levels resembling that of the tendon sheaths with 33% to 50% of the total cell population. CONCLUSIONS: After injury to the deep flexor tendon in a rabbit model, the proportion of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers increases significantly. These findings support the hypothesis that the profibrotic neuropeptide-mast cell-myofibroblast pathway is activated in deep flexor tendon healing.