Håkansson Joakim, Mahlapuu Margit, Ekström Lars, Olmarker Kjell, Wiig Monica
Department of Hand Surgery, and Institution of Surgical Science, Uppsala University, Uppsala, Sweden.
J Hand Surg Am. 2012 Dec;37(12):2519-25. doi: 10.1016/j.jhsa.2012.09.019.
Restoration of digital function after flexor tendon injuries remains a clinical challenge. Complications such as adhesion formation and tendon rupture can lead to limited hand function. The aim of this study was to compare the effects of the lactoferrin-derived peptide, PXL01, formulated in sodium hyaluronate (SH), with SH alone on joint mobility as an indirect measure of postsurgical adhesion prevention and healing strength of the tendon and to elucidate the most optimal concentration of PXL01.
Using a rabbit flexor tendon repair model, in which the deep flexor tendon was fully transected and repaired, PXL01 in SH or SH alone was administered between the repaired tendon and the tendon sheath before closure of the surgical wound. Three concentrations of PXL01 in SH (5, 20, or 40 mg/mL) were compared to determine the lowest effective concentration. The repaired tendons were evaluated 7 weeks after surgery by measuring the proximal interphalangeal joint mobility by full range of flexion assessment and the tendon repair strength.
Treatment with PXL01 formulated in SH resulted in improved mobility of the proximal interphalangeal joint with an average of 10°, corresponding to improvement of approximately 25% to 60% of the flexion of nonoperated toes at the different measuring points compared with SH alone. The difference was statistically significant in 5 out of 6 measuring points (0.5, 1, 2, 3, and 4 N; P < .05). The dose-response study indicated that the lowest effective concentration of PXL01 was 20 mg/mL. There was no difference in healing strength of the tendon between the groups as assessed by load-to-failure breaking strength.
PXL01 in SH significantly improved the mobility compared with the carrier SH alone, without any negative effect on healing strength, and PXL01 at 20 mg/mL was the lowest effective concentration.
The result provides a valuable basis for a clinical trial to assess efficacy and safety of PXL01 in clinical hand surgery.
屈指肌腱损伤后恢复手指功能仍是一项临床挑战。诸如粘连形成和肌腱断裂等并发症可导致手部功能受限。本研究的目的是比较透明质酸钠（SH）配制的乳铁蛋白衍生肽PXL01与单独使用SH对关节活动度的影响，以此作为术后粘连预防和肌腱愈合强度的间接指标，并阐明PXL01的最适浓度。
采用兔屈指肌腱修复模型，其中深屈肌腱完全横断并修复，在手术伤口闭合前，将SH中的PXL01或单独的SH注入修复的肌腱与腱鞘之间。比较SH中三种浓度的PXL01（5、20或40 mg/mL）以确定最低有效浓度。术后7周通过全范围屈曲评估测量近端指间关节活动度和肌腱修复强度，对修复的肌腱进行评估。
用SH配制的PXL01治疗可改善近端指间关节的活动度，平均增加10°，与单独使用SH相比，在不同测量点对应于未手术趾屈曲度提高约25%至60%。6个测量点中的5个（0.5、1、2、3和4 N；P < 0.05）差异具有统计学意义。剂量反应研究表明，PXL01的最低有效浓度为20 mg/mL。通过破坏强度负荷评估，各组之间肌腱的愈合强度没有差异。
与单独的载体SH相比，SH中的PXL01显著改善了关节活动度，对愈合强度没有任何负面影响，20 mg/mL的PXL01是最低有效浓度。
该结果为评估PXL01在临床手部手术中的疗效和安全性的临床试验提供了有价值的依据。
