Department of Hand and Podiatric Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, 130021, People's Republic of China.
Jilin Province Key Laboratory on Tissue Repair, Reconstruction and Regeneration, The First Hospital of Jilin University, Changchun, 130021, People's Republic of China.
Int J Nanomedicine. 2023 Jan 6;18:115-126. doi: 10.2147/IJN.S377600. eCollection 2023.
Topical verapamil has been demonstrated to reduce the fibroproliferative scar. Therefore, it was hypothesized that topical verapamil could reduce adhesion formation after tendon repair. The current study aimed to examine the effects of verapamil-loaded polydopamine nanoparticles (VP-PDA NPs) on the adhesion formation of Achilles tendon laceration and repair in a rat model.
We randomly assigned 72 male Sprague-Dawley rats to the control, the PDA NPs, and the VP-PDA NPs groups (n = 24 per group). The quality of tendon healing was evaluated by the maximal tensile strength four and six weeks after surgery. The degree of tendon adhesion was scored on days 4, 15, 29, and 43 after surgery. The expressions of transforming growth factor-beta 1 (TGF-β1), vimentin, α-smooth muscle actin (α-SMA), and collagens type I and III were detected through Western blotting or immunohistochemistry at four weeks after surgery.
In vitro release tests revealed that 61.3% of verapamil was released from VP-PDA NPs in four weeks. There was a significant increase in average failure to load in the VP-PDA NPs group (89.27 ± 5.09 N) compared with the PDA NPs group (65.52 ± 2.04 N) (p = 0.003) and the control group (74.52 ± 4.24 N) (p = 0.029). Adhesion scores were significantly reduced in the VP-PDA NPs group at six weeks (3.175 ± 0.08) and four weeks (3.35 ± 0.25) compared with the other groups. Moreover, VP-PDA NPs significantly reduced the expression of vimentin, α-SMA, TGF-β1, and collagens type I and III.
These data suggest that VP-PDA NPs reduced adhesion formation and enhanced tendon healing during rat tendon injury. Since topical verapamil has been used in clinics without side effects, VP-PDA NPs would have direct translation implications. However, its anti-adhesive effects on intrasynovial tendon injury must be examined.
局部应用维拉帕米已被证明可减少纤维增生性瘢痕。因此，有人假设局部应用维拉帕米可以减少肌腱修复后的粘连形成。本研究旨在通过大鼠模型检查维拉帕米负载聚多巴胺纳米粒子（VP-PDA NPs）对跟腱撕裂和修复后粘连形成的影响。
我们将 72 只雄性 Sprague-Dawley 大鼠随机分为对照组、PDA NPs 组和 VP-PDA NPs 组（每组 24 只）。术后 4 周和 6 周评估肌腱愈合质量。术后 4、15、29 和 43 天评估肌腱粘连程度。术后 4 周通过 Western blot 或免疫组化检测转化生长因子-β1（TGF-β1）、波形蛋白、α-平滑肌肌动蛋白（α-SMA）和 I 型和 III 型胶原蛋白的表达。
体外释放试验显示，VP-PDA NPs 在 4 周内释放了 61.3%的维拉帕米。VP-PDA NPs 组的平均加载失效显著增加（89.27 ± 5.09 N），与 PDA NPs 组（65.52 ± 2.04 N）（p = 0.003）和对照组（74.52 ± 4.24 N）（p = 0.029）相比。VP-PDA NPs 组在 6 周（3.175 ± 0.08）和 4 周（3.35 ± 0.25）时的粘连评分明显低于其他组。此外，VP-PDA NPs 显著降低了波形蛋白、α-SMA、TGF-β1 和 I 型和 III 型胶原蛋白的表达。
这些数据表明，VP-PDA NPs 减少了大鼠肌腱损伤后的粘连形成并增强了肌腱愈合。由于局部应用维拉帕米在临床上没有副作用，VP-PDA NPs 将具有直接的转化意义。然而，必须检查其对滑膜内肌腱损伤的抗粘连作用。
