Department of Orthopaedic Surgery, Washington University, 660 South Euclid, Campus Box 8233, St. Louis, MO 63110.
J Bone Joint Surg Am. 2010 Oct 6;92(13):2285-93. doi: 10.2106/JBJS.I.01601.
Studies have demonstrated that flexor tendon repair strength fails to increase in the first three weeks following suturing of the tendon, a finding that correlates closely with the timing of many clinical failures. The application of growth factors holds promise for improving the tendon-repair response and obviating failure in the initial three weeks.
The effects of basic fibroblast growth factor on flexor tendon healing were evaluated with use of a canine model. Operative repair followed by the sustained delivery of basic fibroblast growth factor, at two different doses, was compared with operative repair alone. Histological, biochemical, and biomechanical methods were used to evaluate the tendons twenty-one days after repair.
Vascularity, cellularity, and adhesion formation were increased in the tendons that received basic fibroblast growth factor as compared with the tendons that received operative repair alone. DNA concentration was increased in the tendons that received 1000 ng of basic fibroblast growth factor (mean and standard deviation, 5.7 ± 0.7 μg/mg) as compared with the tendons that received 500 ng of basic fibroblast growth factor (3.8 ± 0.7 μg/mg) and the matched control tendons that received operative repair alone (4.5 ± 0.9 μg/mg). Tendons that were treated with basic fibroblast growth factor had a lower ratio of type-I collagen to type-III collagen, indicating increased scar formation compared with that seen in tendons that received operative repair alone (3.0 ± 1.6 in the group that received 500-ng basic fibroblast growth factor compared with 4.3 ± 1.0 in the paired control group that received operative repair alone, and 3.4 ± 0.6 in the group that received 1000-ng basic fibroblast growth factor compared with 4.5 ± 1.9 in the paired control group that received operative repair alone). Consistent with the increases in adhesion formation that were seen in tendons treated with basic fibroblast growth factor, the range of motion was reduced in the group that received the higher dose of basic fibroblast growth factor than it was in the paired control group that received operative repair alone (16.6° ± 9.4° in the group that received 500 ng basic fibroblast growth factor, 13.4° ± 6.1° in the paired control group that received operative repair alone, and 29.2° ± 5.8° in the normal group [i.e., the group of corresponding, uninjured tendons from the contralateral forelimb]; and 15.0° ± 3.8° in the group that received 1000 ng basic fibroblast growth factor, 19.3° ± 5.5° in the paired control group that received operative repair alone, and 29.0° ± 8.8° in the normal group). There were no significant differences in tendon excursion or tensile mechanical properties between the groups that were treated with basic fibroblast growth factor and the groups that received operative repair alone.
Although basic fibroblast growth factor accelerated the cell-proliferation phase of tendon healing, it also promoted neovascularization and inflammation in the earliest stages following the suturing of the tendon. Despite a substantial biologic response, the administration of basic fibroblast growth factor failed to produce improvements in either the mechanical or functional properties of the repair. Rather, increased cellular activity resulted in peritendinous scar formation and diminished range of motion.
研究表明,在肌腱缝合后的前三周内,屈肌腱修复强度没有增加,这一发现与许多临床失败的时间密切相关。生长因子的应用有望改善肌腱修复反应,避免在前三周内失败。
采用犬模型评估碱性成纤维细胞生长因子对屈肌腱愈合的影响。手术修复后,持续给予两种不同剂量的碱性成纤维细胞生长因子,与单独手术修复进行比较。修复后 21 天,采用组织学、生物化学和生物力学方法评估肌腱。
与单独手术修复的肌腱相比,接受碱性成纤维细胞生长因子治疗的肌腱血管生成、细胞增多和粘连形成增加。接受 1000ng 碱性成纤维细胞生长因子治疗的肌腱(平均值和标准差,5.7±0.7μg/mg)的 DNA 浓度高于接受 500ng 碱性成纤维细胞生长因子(3.8±0.7μg/mg)和接受单独手术修复的匹配对照肌腱(4.5±0.9μg/mg)。接受碱性成纤维细胞生长因子治疗的肌腱 I 型胶原与 III 型胶原的比值较低,表明与单独接受手术修复的肌腱相比,疤痕形成增加(接受 500ng 碱性成纤维细胞生长因子治疗的组为 3.0±1.6,与单独接受手术修复的配对对照肌腱组为 4.3±1.0,接受 1000ng 碱性成纤维细胞生长因子治疗的组为 3.4±0.6,与单独接受手术修复的配对对照肌腱组为 4.5±1.9)。与接受碱性成纤维细胞生长因子治疗的肌腱中观察到的粘连形成增加一致,接受较高剂量碱性成纤维细胞生长因子治疗的肌腱的运动范围比单独接受手术修复的配对对照肌腱小(接受 500ng 碱性成纤维细胞生长因子治疗的组为 16.6°±9.4°,单独接受手术修复的配对对照肌腱组为 13.4°±6.1°,正常组[即对侧未受伤前肢的相应肌腱]为 29.2°±5.8°;接受 1000ng 碱性成纤维细胞生长因子治疗的组为 15.0°±3.8°,单独接受手术修复的配对对照肌腱组为 19.3°±5.5°,正常组为 29.0°±8.8°)。接受碱性成纤维细胞生长因子治疗的组与单独接受手术修复的组之间,肌腱活动度或拉伸力学性能没有显著差异。
尽管碱性成纤维细胞生长因子加速了肌腱愈合的细胞增殖阶段,但它也促进了肌腱缝合后早期的新血管形成和炎症。尽管有大量的生物学反应,但碱性成纤维细胞生长因子的给药并没有改善修复的机械或功能特性。相反,细胞活性的增加导致了腱周疤痕形成和运动范围减小。